خاصیت ضد سرطانی ترکیبات فنولی در گیاهان دارویی
محورهای موضوعی : فیتوشیمی
سعید ملائی
1
(گروه شیمی، دانشکده علوم پایه، دانشگاه شهید مدنی آذربایجان، تبریز، ایران)
پوپک فرنیا
2
(ایران، مركز تحقیقات مايكوباكتريولوژي، پژوهشكده سل و بیماريهاي ريوي، مركز آموزشي، پژوهشي و درماني سل و بیماريهاي ريوي بیمارستان دكتر مسیح دانشوري، دانشگاه علوم پزشكي شهید بهشتي، تهران، ايران)
جلال الدین غنوی
3
(مركز تحقیقات مايكوباكتريولوژي، پژوهشكده سل و بیماريهاي ريوي، مركز آموزشي، پژوهشي و درماني سل و بیماريهاي ريوي بیمارستان دكتر مسیح دانشوري، دانشگاه علوم پزشكي شهید بهشتي، تهران، ايران)
علی اکبر ولایتی
4
(مركز تحقیقات مايكوباكتريولوژي، پژوهشكده سل و بیماريهاي ريوي، مركز آموزشي، پژوهشي و درماني سل و بیماريهاي ريوي بیمارستان دكتر مسیح دانشوري، دانشگاه علوم پزشكي شهید بهشتي، تهران، ايران)
کلید واژه: آپوپتوز, سرطان, فلاونوئید, فنول, مکانیسم,
چکیده مقاله :
سرطان تکثیر غیرطبیعی و رشد کنترل نشده سلولی است. عوامل سرطانزا باعث آسیب DNA، کاهش عملکرد ژن سرکوبگر تومور و ایجاد تومور و متاستاز میشود. برخی از عوامل ایجاد سرطان عوامل فیزیکی همچون اشعه ماوراءبنفش، مواد شیمیایی، دود سیگار، رژیم غذایی نامتعادل، عوامل وابسته به شغل، وراثت، هورمونها، عوامل متابولیک و عوامل بیولوژیک به ویژه برخی باکتریها و ویروسها هستند. مهمترین روش درمان سرطان امروزه شیمی درمانی است که عوارض جانبی زیادی دارد و باعث مقاومت دارویی میشود. برخی ازگیاهان سالها به عنوان منبع قابل اعتمادی از عوامل ضدسرطان جهت تولید داروهای ضدسرطان شناخته میشوند. برخی ازگیاهان دارای اثرات پیشگیرانه و درمانی برعلیه سرطان هستند و برخی از آنها میتوانند عوارض جانبی شیمی درمانی و رادیوتراپی را کاهش دهند و نیز اقتصادی هستند. از مهمترین ترکیبات طبیعی موجود در گیاهان که میتوانند دارای خاصیت ضدسرطانی باشند، ترکیبات فنولی هستند. ترکیبات فنولی به گروههای مختلف همچون فنولهای ساده، فلاونوئیدها، کومارینها، فنولیک اسیدها، استیلبن ها و آنتراکینونها طبقه بندی میشوند. مکانیسم اثر ضدسرطانی اغلب این مواد مربوط به خاصیت آنتی اکسیدانی و مهار رشد سلولهای توموری آنهاست. بسیاری از این ترکیبات به طور سنتی در مناطق مختلفی از جهان کاربرد دارند. در این مقاله مروری، ترکیبات فنولی دارای خاصیت ضدسرطان مورد بررسی قرار خواهند گرفت و مهمترین مکانیزمهای اثر آنها معرفی خواهد شد. ما امیدواریم که این مقاله، اطلاعات مفیدی را برای درک پتانسیل گیاهان در تولید ترکیبات ضدسرطانی جدید دراختیار خوانندگان قرار دهد و محققین را به انجام پروژه هایی که میتواند منجربه تولید داروهای جدید ضدسرطانی طبیعی شود، ترغیب نماید.
Cancer is abnormal cell proliferation and uncontrolled cell growth. Carcinogenic factors cause DNA damage, decrease the function of tumor suppressor gene and cause tumor and metastasis. Some of the causes of cancer are physical factors such as ultraviolet rays, chemicals, cigarette smoke, unbalanced diet, occupational factors, heredity, hormones, metabolic factors, and biological factors, especially some bacteria and viruses. The most important method of cancer treatment is chemotherapy, which has many side effects and causes drug resistance. Some plants have been known for years as a reliable and excellent source of anticancer agents for production of anticancer drugs. Some plants have preventive and therapeutic effects against cancer, and some of them can reduce side effects of chemotherapy and radiotherapy, and are also economical. One of the most important natural compounds in plants having anticancer properties are phenolic compounds. Phenolic compounds are classified into different groups such as simple phenole, flavonoids, coumarins, phenolic acids, stilbenes and antraquinones. The mechanism of anticancer effect of most of these substances is related to their antioxidant property and inhibiting the growth of tumor cells. Many of these compounds are traditionally used in different regions of the world. In this review article, phenolic compounds with anticancer properties will be investigated and the most important mechanisms of their effects will be introduced. We hope that this article will provide readers with useful information to understand the potential of plants in producing new anticancer compounds and encourage researchers to undertake projects leading to development of new natural anticancer drugs.
Abotaleb, M., Liskova, A., Kubatka, P. and Büsselberg, D. (2020). Therapeutic potential of plant phenolic acids in the treatment of cancer. Biomolecules. 10(2): 221. # #
Adrian, M., Jeandet, P., Veneau, J., Weston, L.A. and Bessis, R. (1977). Biological activity of resveratrol, a stilbenic compound from grapevines, against Botrytis cinerea, the causal agent for gray mold. Journal of Chemical Ecology. 23: 1689-1702. # #
Afaq, F., Syed, D.N., Malik, A., Hadi, N., Sarfaraz, S., Kweon, M.H., et al. (2007). Delphinidin, an anthocyanidin in pigmented fruits and vegetables, protects human HaCaT keratinocytes and mouse skin against UVB-mediated oxidative stress and apoptosis. Journal of Investigative Dermatology. 127(1): 222-232. # #
Aijaz, M., Keserwani, N., Yusuf, M., Ansari, N.H., Ushal, R. and Kalia, P. (2022). Chemical, biological, and pharmacological prospects of caffeic acid. Biointerface Research in Applied Chemistry. 13: 324. # #
Alam, M., Ahmed, S., Elasbali, A.M., Adnan, M., Alam, S., Hassan, M.I., et al. (2022). Therapeutic implications of caffeic acid in cancer and neurological diseases. Frontiers in Oncology. 12. # #
Al Mamari, H.H. (2021). Phenolic compounds: Classification, chemistry, and updated techniques of analysis and synthesis. Phenolic compounds-chemistry, synthesis, diversity, non-conventional industrial, pharmaceutical and therapeutic applications, 10. # #
Anantharaju, P.G., Gowda, P.C., Vimalambike, M.G. and Madhunapantula, S.V. (2016). An overview on the role of dietary phenolics for the treatment of cancers. Nutrition Journal. 15(1): 1-16. # #
Attoub, S., Sperandio, O., Raza, H., Arafat, K., Al‐Salam, S., Al Sultan, M.A., et al. (2013). Thymoquinone as an anticancer agent: evidence from inhibition of cancer cells viability and invasion in vitro and tumor growth in vivo. Fundamental & Clinical Pharmacology. 27(5): 557-569. # #
Aybastıer, Ö., Dawbaa, S., Demir, C., Akgün, O., Ulukaya, E. and Arı, F. (2018). Quantification of DNA damage products by gas chromatography tandem mass spectrometry in lung cell lines and prevention effect of thyme antioxidants on oxidative induced DNA damage. Mutation Research - Fundamental and Molecular Mechanisms. 808: 1-9. # #
Badhani, B., Sharma, N. and Kakkar, R. (2015). Gallic acid: A versatile antioxidant with promising therapeutic and industrial applications. RSC Advances. 5(35): 27540-27557. # #
Baghel, S.S., Shrivastava, N., Baghel, R.S., Agrawal, P. and Rajput, S. (2012). A review of quercetin: antioxidant and anticancer properties. World Journal of Pharmaceutical Sciences. 1(1): 146-160. # #
Bai, J., Zhang, Y., Tang, C., Hou, Y., Ai, X., Chen, X., et al. (2021). Gallic acid: Pharmacological activities and molecular mechanisms involved in inflammation-related diseases. Biomedical and Pharmacology Journal. 133: 110985. # #
Bakrim, S., El Omari, N., El Hachlafi, N., Bakri, Y., Lee, L.H., et al. (2022). Dietary phenolic compounds as anticancer natural drugs: recent update on molecular mechanisms and clinical trials. Foods. 11(21): 3323. # #
Balasundram, N., Sundram, K. and Samman, S. (2006). Phenolic compounds in plants and agri-industrial by-products: Antioxidant activity, occurrence, and potential uses. Food Chemistry. 99(1): 191-203. # #
Bao, L., Liu, F., Guo, H.B., Li, Y., Tan, B.B., Zhang, W.X. and Peng, Y.H. (2016). Naringenin inhibits proliferation, migration, and invasion as well as induces apoptosis of gastric cancer SGC7901 cell line by downregulation of AKT pathway. Tumor Biology. 37: 11365-11374. # #
Bhavani, P., Subramanian, P. and Kanimozhi, S. (2017). Preventive efficacy of vanillic acid on regulation of redox homeostasis, matrix metalloproteinases and cyclin D1 in rats bearing endometrial carcinoma. Indian Journal of Clinical Biochemistry. 32: 429-436. # #
Bhosale, P.B., Ha, S.E., Vetrivel, P., Kim, H.H., Kim, S.M. and Kim, G.S. (2020). Functions of polyphenols and its anticancer properties in biomedical research: a narrative review. Translational Cancer Research. 9(12): 7619. # #
Bishayee, A. (2009). Cancer Prevention and Treatment with Resveratrol: From Rodent Studies to Clinical TrialsResveratrol and Cancer: In Vivo and Clinical Studies. Cancer Prevention Research. 2(5): 409-418. # #
Boudreau, M.D., Mellick, P.W., Olson, G.R., Felton, R.P., Thorn, B.T. and Beland, F.A. (2013). Clear evidence of carcinogenic activity by a whole-leaf extract of Aloe barbadensis miller (aloe vera) in F344/N rats. Toxicological Sciences. 131(1): 26-39. # #
Bouzaiene, N.N., Jaziri, S.K., Kovacic, H., Chekir-Ghedira, L., Ghedira, K. and Luis, J. (2015). The effects of caffeic, coumaric and ferulic acids on proliferation, superoxide production, adhesion and migration of human tumor cells in vitro. European Journal of Pharmacology. 766: 99-105. # #
Bunea, A., Rugină, D., Sconţa, Z., Pop, R.M., Pintea, A., Socaciu, C., et al. (2013). Anthocyanin determination in blueberry extracts from various cultivars and their antiproliferative and apoptotic properties in B16-F10 metastatic murine melanoma cells. Phytochemistry. 95: 436-444. # #
Cheng, Y.W., Chang, C.Y., Lin, K.L., Hu, C.M., Lin, C.H. and Kang, J.J. (2008). Shikonin derivatives inhibited LPS-induced NOS in RAW 264.7 cells via downregulation of MAPK/NF-κB signaling. Journal of Ethnopharmacology. 120(2): 264-271. # #
Chang, W.C., Hsieh, C.H., Hsiao, M.W., Lin, W.C., Hung, Y.C. and Ye, J.C. (2010). Caffeic acid induces apoptosis in human cervical cancer cells through the mitochondrial pathway. Taiwanese Journal of Obstetrics and Gynecology. 49(4): 419-424. # #
Chen, H.M., Wu, Y.C., Chia, Y.C., Chang, F.R., Hsu, H.K., Hsieh, Y.C., et al. (2009). Gallic acid, a major component of Toona sinensis leaf extracts, contains a ROS-mediated anti-cancer activity in human prostate cancer cells. Cancer Letters. 286(2): 161-71. # #
Chen, X., Yang, L., Oppenheim, J.J. and Howard, O.Z. (2002). Cellular pharmacology studies of shikonin derivatives. Phytotherapy Research. 16(3): 199-209. # #
Chen, X., Yang, L., Zhang, N., Turpin, J.A., Buckheit, R.W., Osterling, C., et al. (2003). Shikonin, a component of Chinese herbal medicine, inhibits chemokine receptor function and suppresses human immunodeficiency virus type 1. Antimicrobial Agents and Chemotherapy. 47(9): 2810-2816. # #
Dastjerdi, M.N., Mehdiabady, E.M., Iranpour, F.G., Bahramian, H. (2016). Effect of Thymoquinone on P53 gene expression and consequence apoptosis in breast cancer cell line. International Journal of Preventive Medicine. 14(7): 66. doi: 10.4103/2008-7802.180412. # #
De Oliveira, C.B., Comunello, L.N., Maciel, É.S., Giubel, S.R., Bruno, A.N., Chiela, E.C., et al. (2013). The inhibitory effects of phenolic and terpenoid compounds from Baccharis trimera in Siha cells: differences in their activity and mechanism of action. Molecules. 18(9): 11022-11032. # #
Di Carlo, G., Mascolo, N., Izzo, A.A. and Capasso, F. (1999). Flavonoids: old and new aspects of a class of natural therapeutic drugs. Life Sciences. 65(4): 337-353. # #
El-Hawary, S.S., Sayed, A.M., Mohammed, R., Hassan, H.M., Zaki, M.A., Rateb, M.E., et al. (2018). Epigenetic modifiers induce bioactive phenolic metabolites in the marine-derived fungus Penicillium brevicompactum. Marine Drugs. 16(8): 253. # #
Eroğlu, C., Avcı, E., Vural, H. and Kurar, E. (2018). Anticancer mechanism of Sinapic acid in PC-3 and LNCaP human prostate cancer cell lines. Genes. 671: 127-134. # #
Eroğlu, C., Seçme, M., Bağcı, G. and Dodurga, Y. (2015). Assessment of the anticancer mechanism of ferulic acid via cell cycle and apoptotic pathways in human prostate cancer cell lines. Tumor Biology. 36: 9437-9446. # #
Espíndola, K.M.M., Ferreira, R.G., Narvaez, L.E.M., Silva Rosario, A.C.R., Da Silva, A.H.M., Silva, A.G.B., et al. (2019). Chemical and pharmacological aspects of caffeic acid and its activity in hepatocarcinoma. Frontiers in Oncology. 541. # #
Fahrioğlu, U., Dodurga, Y., Elmas, L. and Seçme, M. (2016). Ferulic acid decreases cell viability and colony formation while inhibiting migration of MIA PaCa-2 human pancreatic cancer cells in vitro. Gene. 576(1): 476-482. # #
Fan, K., Li, X., Cao, Y., Qi, H., Li, L., Zhang, Q. and Sun, H. (2015). Carvacrol inhibits proliferation and induces apoptosis in human colon cancer cells. Anti-cancer Drug. 26(8): 813-823. # #
Fang, J., Xia, C., Cao, Z., Zheng, J.Z., Reed, E. and Jiang, B.H. (2005). Apigenin inhibits VEGF and HIF‐1 expression via PI3K/AKT/p70S6K1 and HDM2/p53 pathways. FASEB Journal1. 9(3): 342-353. # #
Gali-Muhtasib, H., Diab-Assaf, M., Boltze, C., Al-Hmaira, J., Hartig, R., Roessner, A., et al. (2004). Thymoquinone extracted from black seed triggers apoptotic cell death in human colorectal cancer cells via a p53-dependent mechanism. International Journal of Oncology. 25(4): 857-866. # #
Ghasemzadeh, A. and Jaafar, H.Z. (2013). Profiling of phenolic compounds and their antioxidant and anticancer activities in pandan (Pandanus amaryllifolius Roxb.) extracts from different locations of Malaysia. BMC Complementary and Alternative Medicine. 13: 1-9. # #
Gong, J., Zhou, S. and Yang, S. (2019). Vanillic acid suppresses HIF-1α expression via inhibition of mTOR/p70S6K/4E-BP1 and Raf/MEK/ERK pathways in human colon cancer HCT116 cells. International Journal of Molecular Sciences. 20(3): 465. # #
Grigalius, I. and Petrikaite, V. (2017). Relationship between antioxidant and anticancer activity of trihydroxyflavones. Molecules. 22(12): 2169. # #
Hamiza, O.O., Rehman, M.U., Khan, R., Tahir, M., Khan, A.Q., Lateef, A. and Sultana, S. (2014). Chemopreventive effects of aloin against 1, 2-dimethylhydrazine-induced preneoplastic lesions in the colon of Wistar rats. Human & Experimental Toxicology. 33(2): 148-163. # #
Han, G., Xia, J., Gao, J., Inagaki, Y., Tang, W. and Kokudo, N. (2015). Anti-tumor effects and cellular mechanisms of resveratrol. Drug Discoveries & Therapeutics. 9(1): 1-12. # #
Haron, A.S., Syed Alwi, S.S., Saiful Yazan, L., Abd Razak, R., Ong, Y.S., Zakarial Ansar, F.H., et al. (2018). Cytotoxic effect of thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) on liver cancer cell integrated with hepatitis B genome, Hep3B. Evidence-Based Complementary and Alternative Medicine. 2018. # #
Hostetler, G.L., Ralston, R.A. and Schwartz, S.J. (2017). Flavones: Food sources, bioavailability, metabolism, and bioactivity. Advances in Nutrition. 8(3): 423-435. # #
Hu, W., Guan, Y. and Feng, K. (2022). Biosynthesis of phenolic compounds and antioxidant activity in fresh-cut fruits and vegetables. Frontiers in Microbiology. 1782. # #
Hu, J., Lin, S., Huang, J.J. and Cheung, P.C. (2018). Mechanistic study of the in vitro and in vivo inhibitory effects of protocatechuic acid and syringic acid on VEGF-induced angiogenesis. Journal of Agricultural and Food Chemistry. 66(26): 6742-6751. # #
Hurson, A.N., Ahearn, T.U., Keeman, R., Abubakar, M., Jung, A.Y., Kapoor, P.M., et al. (2022). Systematic literature review of risk factor associations with breast cancer subtypes in women of African, Asian, Hispanic, and European descents. Cancer Research. 82(12): 3670. # #
Imran, M., Salehi, B., Sharifi-Rad, J., Aslam Gondal, T., Saeed, F., Imran, A., et al. (2019). Kaempferol: A key emphasis to its anticancer potential. Molecules. 24(12): 2277. # #
Islam, M.T., Khalipha, A.B., Bagchi, R., Mondal, M., Smrity, S.Z., Uddin, S.J., et al. (2019). Anticancer activity of Thymol: A literature‐based review and docking study with Emphasis on its anticancer mechanisms. IUBMB life. 71(1): 9-19. # #
Islam, B.U., Suhail, M., Khan, M.K., Zughaibi, T.A., Alserihi, R.F., Zaidi, S.K., et al. (2021). Polyphenols as anticancer agents: Toxicological concern to healthy cells. Phytotherap Research. 35(11): 6063-6079. # #
Jang, Y.G., Hwang, K.A. and Choi, K.C. (2018). Rosmarinic acid, a component of rosemary tea, induced the cell cycle arrest and apoptosis through modulation of HDAC2 expression in prostate cancer cell lines. Nutrients. 10(11): 1784. # #
Jin, B.R., Chung, K.S., Hwang, S., Hwang, S.N., Rhee, K.J., Lee, M. and An, H.J. (2021). Rosmarinic acid represses colitis-associated colon cancer: A pivotal involvement of the TLR4-mediated NF-κB-STAT3 axis. Neoplasia. 23(6): 561-573. # #
Jitareanu, A., Padureanu, S., Tataringa, G., Tuchilus, C. and Stanescu, U. (2013). Evaluation of phytotoxic and mutagenic effects of some cinnamic acid derivatives using the Triticum test. Turkish Journal of Biology. 37(6): 748-756. # #
Kahkeshani, N., Farzaei, F., Fotouhi, M., Alavi, S.S., Bahramsoltani, R., Naseri, R., et al. (2019). Pharmacological effects of gallic acid in health and diseases: A mechanistic review. Iranian Journal of Basic Medical Sciences. 22(3): 225. # #
Kakkar, S. and Bais, S. (2014). A review on protocatechuic acid and its pharmacological potential. International Scholarly Research Notices. 2014. # #
Khan, A.U., Dagur, H.S., Khan, M., Malik, N., Alam, M. and Mushtaque, M. (2021). Therapeutic role of flavonoids and flavones in cancer prevention: Current trends and future perspectives. European Journal of Medicinal Chemistry Reports. 3: 100010. # #
Kim, J.H., Kim, H., Bak, Y., Kang, J.W., Lee, D.H., Kim, M.S., et al. (2012). Naringenin derivative diethyl (5, 4′-dihydroxy flavanone-7-yl) phosphate inhibits cell growth and induces apoptosis in A549 human lung cancer cells. Journal of the Korean Society for Applied Biological Chemistry. 55: 75-82. # #
Kim, M.S., Lee, C.W., Kim, J.H., Lee, J.C. and An, W.G. (2019). Extract of Rhus verniciflua Stokes induces p53-mediated apoptosis in MCF-7 breast cancer cells. Evidence-Based Complementary and Alternative Medicine. 2019. # #
Kiokias, S., Proestos, C. and Oreopoulou, V. (2020). Phenolic acids of plant origin—A review on their antioxidant activity in vitro (o/w emulsion systems) along with their in-vivo health biochemical properties. Foods. 9(4):534. # #
Kong, J.M., Chia, L.S., Goh, N.K., Chia, T.F. and Brouillard, R. (2003). Analysis and biological activities of anthocyanins. Phytochemistry. 64(5): 923-933. # #
Kopustinskiene, D.M., Jakstas, V., Savickas, A. and Bernatoniene, J. (2020). Flavonoids as anticancer agents. Nutrients. 12(2): 457. # #
Krakowsky, R.H. and Tollefsbol, T.O. (2015). Impact of nutrition on non-coding RNA epigenetics in breast and gynecological cancer. Frontiers in Nutrition. 2: 16. # #
Kumar, N. and Goel, N. (2019). Phenolic acids: Natural versatile molecules with promising therapeutic applications. Biotechnology Reports. 24: e00370. # #
Kumar, S. and Pandey, A.K. (2013). Chemistry and biological activities of flavonoids: an overview. The Scientific World Journal. 2013: 162750. doi: 10.1155/2013/162750. # #
Kurata, R., Adachi, M., Yamakawa, O. and Yoshimoto, M. (2007). Growth suppression of human cancer cells by polyphenolics from sweetpotato (Ipomoea batatas L.) leaves. Journal of Agricultural and Food Chemistry. 55(1): 185-190. # #
Lattanzio, V. (2013). Phenolic compounds: introduction. Natural Products. 50: 1543-1580. # #
Lee, Y.J., Seo, M.J., Lee, O.H., Kim, K.J. and Lee, B.Y. (2017). Hesperetin inhibits lipid accumulation and ROS production during adipocyte differentiation in 3T3‐L1 cells. Journal of Food Biochemistry. 41(3): e12348. # #
Li, X.X., Liu, C., Dong, S.L., Ou, C.S., Lu, J.L., Ye, J.H., et al. (2022). Anticarcinogenic potentials of tea catechins. Frontiers in Nutrition. 9: 3024. # #
Li, H.Q., Luo, Y. and Qiao, C.H. (2012). The mechanisms of anticancer agents by genistein and synthetic derivatives of isoflavone. Mini-Reviews in Medicinal Chemistry. 12(4): 350-362. # #
Lim, W., Park, S., Bazer, F.W. and Song, G. (2017). Naringenin‐induced apoptotic cell death in prostate cancer cells is mediated via the PI3K/AKT and MAPK signaling pathways. Journal of Cellular Biochemistry. 118(5): 1118-1131. # #
Lin, H.H., Chen, J.H., Chou, F.P. and Wang, C.J. (2011). Protocatechuic acid inhibits cancer cell metastasis involving the down‐regulation of Ras/Akt/NF‐κB pathway and MMP‐2 production by targeting RhoB activation. British Journal of Pharmacology. 162(1): 237-254. # #
Liu, Y.M., Jiang, B., Bao, Y.M. and An, L.J. (2008). Protocatechuic acid inhibits apoptosis by mitochondrial dysfunction in rotenone-induced PC12 cells. Toxicology in Vitro. 22(2): 430-437. # #
Lin, M.L., Lu, Y.C., Su, H.L., Lin, H.T., Lee, C.C., Kang, S.E., et al. (2011). Destabilization of CARP mRNAs by aloe‐emodin contributes to caspase‐8‐mediated p53‐independent apoptosis of human carcinoma cells. Journal of Cellular Biochemistry. 112(4): 1176-1191. # #
Lin, D., Xiao, M., Zhao, J., Li, Z., Xing, B., Li, X., et al. (2016). An overview of plant phenolic compounds and their importance in human nutrition and management of type 2 diabetes. Molecules. 21(10): 1374. # #
Liu, Y., Yan, H., Yu, B., He, J., Mao, X., Yu, J., et al. (2022). Protective Effects of Natural Antioxidants on Inflammatory Bowel Disease: Thymol and Its Pharmacological Properties. Antioxidant. 11(10): 1947. # #
Lotfizadeh, V., Mollaei, S. and Hazrati, S. (2021). Biological Activities of Aloin-rich Extracts Obtained from Aloe vera L. Journal of Medicinal plants and By-product. # #
Luo, Y., Ma, Z., Xu, X., Qi, H., Cheng, Z. and Chen, L. (2020). Anticancer effects of rosmarinic acid in human oral cancer cells is mediated via endoplasmic reticulum stress, apoptosis, G2/M cell cycle arrest and inhibition of cell migration. Journal of Balkan Union of Oncology. 25: 1245-1250. # #
Mahmoud, M.A., Okda, T.M., Omran, G.A. and Abd-Alhaseeb, M.M. (2021). Rosmarinic acid suppresses inflammation, angiogenesis, and improves paclitaxel induced apoptosis in a breast cancer model via NF3 κB-p53-caspase-3 pathways modulation. Journal of Applied Biomedicine. 19(4). # #
Masaldan, S. and Iyer, V.V. (2014). Exploration of effects of emodin in selected cancer cell lines: enhanced growth inhibition by ascorbic acid and regulation of LRP1 and AR under hypoxia‐like conditions. Journal of Applied Toxicology. 34(1): 95-104. # #
Matluobi, D., Araghi, A., Maragheh, B.F.A., Rezabakhsh, A., Soltani, S., Khaksar, M., et al. (2018). Carvacrol promotes angiogenic paracrine potential and endothelial differentiation of human mesenchymal stem cells at low concentrations. Microvascular Research. 115: 20-27. # #
Messeha, S.S., Zarmouh, N.O., Asiri, A. and Soliman, K.F. (2020). Rosmarinic acid-induced apoptosis and cell cycle arrest in triple-negative breast cancer cells. European Journal of Pharmacology. 885: 173419. # #
Min, J., Shen, H., Xi, W., Wang, Q., Yin, L., Zhang, Y., et al. (2018). Synergistic anticancer activity of combined use of caffeic acid with paclitaxel enhances apoptosis of non-small-cell lung cancer H1299 cells in vivo and in vitro. Cellular Physiology and Biochemistry. 48(4): 1433-1442. # #
Mitra, S. and Dash, R. (2018). Natural products for the management and prevention of breast cancer. Evidence-Based Complementary and Alternative Medicine. 2018. # #
Mollaei, S., Eslami, M. and Ebadi, M. (2022). Investigation of phenolic compounds and biological properties of vegetative organs of Lepdium vesicarium L. The Quarterly Scientific Journal of Applied Biology. 35(3). # #
Mollaei, S., Ghanavi, J., Farnia, P., Abedi-Ghobadloo, P. and Velayati, A.A. (2021). Antioxidant, antibacterial, and cytotoxic activities of different parts of Salsola vermiculata. Biomedical and Biotechnology Research Journal. 5(3): 307. # #
Mollaei, S., Hazrati, S., Lotfizadeh, V., Dastan, D. and Asgharian, P. (2020). Phytochemical variation and biological activities of Zosima absinthifolia during various stages of growth. International Journal of Food Properties. 23(1): 1556-1567. # #
Mollaei, S., Khanehbarndaz, O., Gerami-Khashal, Z. and Ebadi, M. (2019). Molecular identification and phytochemical screening of endophytic fungi isolated from Lithospermum officinale L. roots: A new source of shikonin. Phytochemistry. 168: 112116. # #
Motaghed, M., Al-Hassan, F.M. and Hamid, S.S. (2013). Cellular responses with thymoquinone treatment in human breast cancer cell line MCF-7. Pharmaceutical Research. 5(3): 200. # #
Naidu, P.V.S., Kinthada, P.M.M.S., Kalyani, P. and Muralidhar, P. (2012). Characterization and biological activities of quercetin thiosemicarbazone derivatives: potential anti-cancer drugs. International Journal of Pharmaceutical and Bio Medical Science. 3(2): 24-27. # #
Nićiforović, N. and Abramovič, H. (2014). Sinapic acid and its derivatives: natural sources and bioactivity. Comprehensive Reviews in Food Science and Food Safety. 13(1): 34-51. # #
Niero, E.L.D.O. and Machado-Santelli, G.M. (2013). Cinnamic acid induces apoptotic cell death and cytoskeleton disruption in human melanoma cells. Journal of Experimental and Clinical Cancer Research. 32(1): 1-14. # #
Nishikawa, T., Nakajima, T., Moriguchi, M., Jo, M., Sekoguchi, S., Ishii, M., et al. (2006). A green tea polyphenol, epigalocatechin-3-gallate, induces apoptosis of human hepatocellular carcinoma, possibly through inhibition of Bcl-2 family proteins. Journal of Hepatology. 44(6): 1074-1082. # #
Nishiumi, S., Miyamoto, S., Kawabata, K., Ohnishi, K., Mukai, R., Murakami, A., et al. (2011). Dietary flavonoids as cancer-preventive and therapeutic biofactors. Frontiers in Bioscience-Scholar. 3(4): 1332-1362. # #
Pan, Q., Pan, H., Lou, H., Xu, Y. and Tian, L. (2013). Inhibition of the angiogenesis and growth of Aloin in human colorectal cancer in vitro and in vivo. Cancer Cell International. 13(1): 1-9. # #
Park, J.H., Jin, C.Y., Lee, B.K., Kim, G.Y., Choi, Y.H. and Jeong, Y.K. (2008). Naringenin induces apoptosis through downregulation of Akt and caspase-3 activation in human leukemia THP-1 cells. Food and Chemical Toxicology. 46(12): 3684-3690. # #
Pontiki, E., Hadjipavlou-Litina, D., Litinas, K. and Geromichalos, G. (2014). Novel cinnamic acid derivatives as antioxidant and anticancer agents: Design, synthesis and modeling studies. Molecules. 19(7): 9655-9674. # #
Pratyusha, S. (2022). Phenolic compounds in the plant development and defense: an overview. Plant Stress Physiology-Perspect Agriculture. doi: 10.5772/intechopen.102873. # #
Qattan, M.Y., Khan, M.I., Alharbi, S.H., Verma, A.K., Al-Saeed, F.A., Abduallah, A.M. and Al Areefy, A.A. (2022). Therapeutic importance of Kaempferol in the treatment of cancer through the modulation of cell signalling pathways. Molecules. 27(24): 8864. # #
Quinn, L., Gray, S.G., Meaney, S., Finn, S., Kenny, O. and Hayes, M. (2017). Sinapinic and protocatechuic acids found in rapeseed: Isolation, characterisation and potential benefits for human health as functional food ingredients. Irish Journal of Agricultural and Food Research. 56(1): 104-119. # #
Ravindranath, M.H., Muthugounder, S., Presser, N. and Viswanathan, S. (2004). Anticancer therapeutic potential of soy isoflavone, genistein. Complementary and Alternative Approaches to Biomedicine. 121-165. # #
Rosa, L.D.S., Silva, N.J.A., Soares, N.C.P., Monteiro, M.C. and Teodoro, A.J. (2016). Anticancer properties of phenolic acids in colon cancer–a review. Journal of Nutrition & Food Sciences. 6(2): 1000468. # #
Rosero, S., Del Pozo, F., Simbaña, W., Álvarez, M., Quinteros, M.F., Carrillo, W., et al. (2022). Polyphenols and flavonoids composition, anti-inflammatory and antioxidant properties of Andean Baccharis macrantha extracts. Plants. 11(12): 1555. # #
Ruwizhi, N. and Aderibigbe, B.A. (2020). Cinnamic acid derivatives and their biological efficacy. International Journal of Molecular Sciences. 21(16): 5712. # #
Saenglee, S., Jogloy, S., Patanothai, A., Leid, M., and Senawong, T. (2016). Cytotoxic effects of peanut phenolics possessing histone deacetylase inhibitory activity in breast and cervical cancer cell lines. Pharmacological Reports. 68: 1102-1110. # #
Sakai, T., Eskander, R.N., Guo, Y., Kim, K.J., Mefford, J., Hopkins, J., et al. (2012). Flavokawain B, a kava chalcone, induces apoptosis in synovial sarcoma cell lines. The Journal of Orthopaedic Research. 30(7): 1045-1050. # #
Sakamoto, T., Horiguchi, H., Oguma, E. and Kayama, F. (2010). Effects of diverse dietary phytoestrogens on cell growth, cell cycle and apoptosis in estrogen-receptor-positive breast cancer cells. The Journal of Nutritional Biochemistry. 21(9): 856-864. # #
Salehi, B., Quispe, C., Chamkhi, I., El Omari, N., Balahbib, A., Sharifi-Rad, J., et al. (2021). Pharmacological properties of chalcones: a review of preclinical including molecular mechanisms and clinical evidence. Frontiers in Pharmacology. 11: 592654. # #
Salehi, B., Sharifi-Rad, J., Cappellini, F., Reiner, Ž., Zorzan, D., Imran, M., et al. (2020). The therapeutic potential of anthocyanins: current approaches based on their molecular mechanism of action. Frontiers in Pharmacology. 11: 1300. # #
Schneider, Y., Duranton, B., Goss, F., Schleiffer, R., Seiler, N. and Raul, F. (2001). Resveratrol inhibits intestinal tumorigenesis and modulates host-defense-related gene expression in an animal model of human familial adenomatous polyposis. Nutrition and Cancer. 39(1): 102-107. # #
Semaming, Y., Pannengpetch, P., Chattipakorn, S.C. and Chattipakorn, N. (2015). Pharmacological properties of protocatechuic acid and its potential roles as complementary medicine. Evidence-Based Complementary and Alternative Medicine. 2015. # #
Senawong, T., Khaopha, S., Misuna, S., Komaikul, J., Senawong, G., Wongphakham, P. and Yunchalard, S. (2014). Phenolic acid composition and anticancer activity against human cancer cell lines of the commercially available fermentation products of Houttuynia cordata. ScienceAsia. 40(6): 420-427. # #
Shankar, E., Goel, A., Gupta, K. and Gupta, S. (2017). Plant flavone apigenin: an emerging anticancer agent. Current Pharmacology Reports. 3: 423-446. # #
Shin, S.Y., Yoon, H., Ahn, S., Kim, D.W., Bae, D.H., Koh, D., et al. (2013). Structural properties of polyphenols causing cell cycle arrest at G1 phase in HCT116 human colorectal cancer cell lines. International Journal of Molecular Sciences. 14(8): 16970-16985. # #
Singh, B.N., Shankar, S. and Srivastava, R.K. (2011). Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. Biochemical Pharmacology. 82(12): 1807-1821. # #
Sinha, D., Sarkar, N., Biswas, J. and Bishayee, A. (2016). Resveratrol for breast cancer prevention and therapy: Preclinical evidence and molecular mechanisms. In: Seminars in cancer biology. Academic Press. 40: 209-232. # #
Sitarek, P., Skała, E., Toma, M., Wielanek, M., Szemraj, J., Skorski, T., et al. (2017). Transformed root extract of Leonurus sibiricus induces apoptosis through intrinsic and extrinsic pathways in various grades of human glioma cells. Pathology and Oncology Research. 23: 679-687. # #
Spilioti, E., Jaakkola, M., Tolonen, T., Lipponen, M., Virtanen, V., Chinou, I., et al. (2014). Phenolic acid composition, antiatherogenic and anticancer potential of honeys derived from various regions in Greece. PloS one. 9(4): e94860. # #
Staniforth, V., Wang, S.Y., Shyur, L.F. and Yang, N.S. (2004). Shikonins, phytocompounds from Lithospermum erythrorhizon, inhibit the transcriptional activation of human tumor necrosis factor α promoter in vivo. Journal of Biological Chemistry. 279(7): 5877-5885. # #
Stopsack, K.H., Nandakumar, S., Arora, K., Nguyen, B., Vasselman, S.E., Nweji, B., et al. (2022). Differences in prostate cancer genomes by self-reported race: contributions of genetic ancestry, modifiable cancer risk factors, and clinical factors racial differences in prostate cancer genomes. Clinical Cancer Research. 28(2): 318-326. # #
Suboj, P., Babykutty, S., Gopi, D.R.V., Nair, R.S., Srinivas, P. and Gopala, S. (2012). Aloe emodin inhibits colon cancer cell migration/angiogenesis by downregulating MMP-2/9, RhoB and VEGF via reduced DNA binding activity of NF-κB. European Journal of Pharmaceutical Sciences. 45(5): 581-591. # #
Szliszka, E., Jaworska, D., Kłósek, M., Czuba, Z.P. and Król, W. (2012). Targeting death receptor TRAIL-R2 by chalcones for TRAIL-induced apoptosis in cancer cells. International Journal of Molecular Sciences. 13(11): 15343-15359. # #
Taghavi, D., Majidi, M., Mollaei, S. and Panahi, B. (2020). Effect of methyl jasmonate on expression of some genes related to shikonin biosynthetic pathway in Lithospermum officinale. Journal of Plant Molecular Breeding. 8(2): 1-9. # #
Tan, D.A. and Dayu, A.R.B. (2022). Menopausal hormone therapy: why we should no longer be afraid of the breast cancer risk. Climacteric. 25(4): 362-368. # #
Taner, G., Özkan Vardar, D., Aydin, S., Aytaç, Z., Başaran, A. and Başaran, N. (2017). Use of in vitro assays to assess the potential cytotoxic, genotoxic and antigenotoxic effects of vanillic and cinnamic acid. Drug and Chemical Toxicology. 40(2): 183-190. # #
Tehami, W., Nani, A., Khan, N.A. and Hichami, A. (2023). New Insights into the anticancer effects of p-Coumaric Acid: Focus on Colorectal Cancer. Dose-Response, 21(1):15593258221150704. # #
Teka, T., Zhang, L., Ge, X., Li, Y., Han, L. and Yan, X. (2022). Stilbenes: Source plants, chemistry, biosynthesis, pharmacology, application and problems related to their clinical Application-A comprehensive review. Phytochemistry. 197: 113128. # #
Tekale, S., Mashele, S., Pooe, O., Thore, S., Kendrekar, P. and Pawar, R. (2020). Biological role of chalcones in medicinal chemistry. In: Vector-borne diseases-recent developments in epidemiology and control, pp. 1-18. Ed. D. Claborn. Rijeka: IntechOpen. # #
Tseng, T.H., Kao, T.W., Chu, C.Y., Chou, F.P., Lin, W.L. and Wang, C.J. (2000). Induction of apoptosis by hibiscus protocatechuic acid in human leukemia cells via reduction of retinoblastoma (RB) phosphorylation and Bcl-2 expression. Biochemical Pharmacology. 60(3): 307-315. # #
Tsimogiannis, D. and Oreopoulou, V. (2019). Classification of Phenolic Compounds in Plants. In: Polyphenols in Plants, pp. 263–284. Amsterdam, The Netherlands: Elsevier. # #
Turan, I., Demir, S., Aliyazicioglu, R., Kilinc, K., Ozer Yaman, S., Akbulut Cakiroglu, K., et al. (2019). Dimethyl sulfoxide extract of Dianthus carmelitarum induces S phase arrest and apoptosis in human colon cancer cells. Nutrition and Cancer. 71(7): 1181-1188. # #
Valanciene, E., Jonuskiene, I., Syrpas, M., Augustiniene, E., Matulis, P., Simonavicius, A., et al. (2020). Advances and prospects of phenolic acids production, biorefinery and analysis. Biomoleculas. 10(6): 874. # #
Velli, S.K., Sundaram, J., Murugan, M., Balaraman, G. and Thiruvengadam, D. (2019). Protective effect of vanillic acid against benzo (a) pyrene induced lung cancer in Swiss albino mice. Journal of Biochemical and Molecular Toxicology. 33(10): e22382. # #
Vermerris, W. and Nicholson, R. (2008). Phenolic Compound Biochemistry. Berlin: Springer. ISBN 978-1-4020-5163-0. # #
Vidak, M., Rozman, D. and Komel, R. (2015). Effects of flavonoids from food and dietary supplements on glial and glioblastoma multiforme cells. Molecules. 20(10): 19406-19432. # #
Vrhovac Madunić, I., Madunić, J., Antunović, M., Paradžik, M., Garaj-Vrhovac, V., Breljak, D., et al. (2018). Apigenin, a dietary flavonoid, induces apoptosis, DNA damage, and oxidative stress in human breast cancer MCF-7 and MDA MB-231 cells. Naunyn-Schmiedeberg's Archives of Pharmacology. 391: 537-550. # #
Wahle, K.W., Brown, I., Rotondo, D. and Heys, S.D. (2010). Plant phenolics in the prevention and treatment of cancer. Bio-farms for nutraceuticals: functional food and safety control by biosensors. 2010: 36-51. # #
Wang, T., Gong, X., Jiang, R., Li, H., Du, W. and Kuang, G. (2016). Ferulic acid inhibits proliferation and promotes apoptosis via blockage of PI3K/Akt pathway in osteosarcoma cell. American Journal of Translational Research. 8(2): 968. # #
Wang, F., Mayca Pozo, F., Tian, D., Geng, X., Yao, X., Zhang, Y. and Tang, J. (2020). Shikonin inhibits cancer through P21 upregulation and apoptosis induction. Frontiers in Pharmacology. 11: 861. # #
Wang, L., Yang, H., Wang, C., Shi, X. and Li, K. (2019). Rosmarinic acid inhibits proliferation and invasion of hepatocellular carcinoma cells SMMC 7721 via PI3K/AKT/mTOR signal pathway. Biomedicine & Pharmacotherapy. 120: 109443. # #
Way, T.D., Kao, M.C. and Lin, J.K. (2004). Apigenin induces apoptosis through proteasomal degradation of HER2/neu in HER2/neu-overexpressing breast cancer cells via the phosphatidylinositol 3-kinase/Akt-dependent pathway. Journal of Biological Chemistry. 279(6): 4479-4489. # #
Xie, Z., Guo, Z., Wang, Y., Lei, J. and Yu, J. (2018). Protocatechuic acid inhibits the growth of ovarian cancer cells by inducing apoptosis and autophagy. Phytotherapy Research. 32(11): 2256-2263. # #
Xing, N., Chen, Y., Mitchell, S.H. and Young, C.Y. (2001). Quercetin inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells. Carcinogenesis. 22(3): 409-414. # #
Yadav, S., Sharma, A., Nayik, G.A., Cooper, R., Bhardwaj, G., Sohal, H.S., et al. (2022). Review of shikonin and derivatives: isolation, chemistry, biosynthesis, pharmacology and toxicology. Frontiers in Pharmacology. 13: 905755. # #
Yang, G.W., Jiang, J.S. and Lu, W.Q. (2015). Ferulic acid exerts anti-angiogenic and anti-tumor activity by targeting fibroblast growth factor receptor 1-mediated angiogenesis. International Journal of Molecular Sciences. 16(10): 24011-24031. # #
Yang, L., Su, L., Cao, C., Xu, L., Zhong, D., Xu, L. and Liu, X. (2013). The chalcone 2′‐hydroxy‐4′, 5′‐dimethoxychalcone activates death receptor 5 pathway and leads to apoptosis in human nonsmall cell lung cancer cells. IUBMB life. 65(6): 533-543. # #
Ye, L., Chan, F.L., Chen, S. and Leung, L.K. (2012). The citrus flavonone hesperetin inhibits growth of aromatase-expressing MCF-7 tumor in ovariectomized athymic mice. The Journal of Nutritional Biochemistry. 23(10): 1230-1237. # #
Yip, E.C.H., Chan, A.S.L., Pang, H., Tam, Y.K. and Wong, Y.H. (2006). Protocatechuic acid induces cell death in HepG2 hepatocellular carcinoma cells through a c-Jun N-terminal kinase-dependent mechanism. Cell Biology and Toxicology. 22: 293-302. # #
Zhang, Y., Cai, P., Cheng, G. and Zhang, Y. (2022). A brief review of phenolic compounds identified from plants: Their extraction, analysis, and biological activity. Natural Product Communication. 17(1):1934578X211069721. # #
Zhang, X., Lin, D., Jiang, R., Li, H., Wan, J. and Li, H. (2016). Ferulic acid exerts antitumor activity and inhibits metastasis in breast cancer cells by regulating epithelial to mesenchymal transition. Oncology Reports. 36(1): 271-278. # #
Zhang, J., Wu, D., Vikash Song, J., Wang, J., Yi, J. and Dong, W. (2015). Hesperetin induces the apoptosis of gastric cancer cells via activating mitochondrial pathway by increasing reactive oxygen species. Digestive Diseases and Sciences. 60: 2985-2995. # #
Zhang, X.D., Wu, Q. and Yang, S.H. (2017). Ferulic acid promoting apoptosis in human osteosarcoma cell lines. Pakistan Journal of Medical Sciences. 33(1): 127. # #
Zhao, B. and Hu, M. (2013). Gallic acid reduces cell viability, proliferation, invasion and angiogenesis in human cervical cancer cells. Oncology Letters. 6(6): 1749-1755. # #
Zhou, Y., Zheng, J., Li, Y., Xu, D.P., Li, S., Chen, Y.M., et al. (2016). Natural polyphenols for prevention and treatment of cancer. Nutrients. 8(8): 515. # #
