Anti-tumor effects of Silybum marianum essential oil and 5-fluorouracil combination on Hepatocellular carcinoma cells (HepG2)

Subject Areas : Journal of Animal Biology

Mohammad Jaber Masoud Khooy ¹ , Mohammadreza Salehi Salmi ² , Massoumeh Farasat ³ , Hamed Mirzaei ⁴

1 - Department of Horticulture, Ahvaz Islamic Azad University, Science and Research Branch, Ahvaz, Iran
2 - Visiting Professor, Department of Horticulture, Ahvaz Branch, Islamic Azad University, Ahvaz, Iran and Faculty Member, Department of Horticulture, Faculty of Agriculture, Khuzestan University of Agricultural Sciences and Natural Resources, Ahvaz, Iran
3 - Department of Horticulture, Ahvaz Islamic Azad University, Science and Research Branch, Ahvaz, Iran
4 - Visiting Professor, Department of Horticulture, Ahvaz Branch, Islamic Azad University, Ahvaz, Iran and Faculty Member of Biochemistry and Nutrition Research Center in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran

Received: 2021-08-17 Accepted : 2021-09-11 Published : 2022-05-22

Keywords: angiogenesis, 5-Fluorouracil, hepatocellular carcinoma, Silybum marianum essential oil, Combination therapy,

Abstract :

The present study evaluated the efficacy of combining 5-fluorouracil (5-FU) and Silybum marianum essential oils to suppress in vitro Hepatocellular carcinoma (HCC) growth by influencing the Wnt, NF-κB, angiogenesis, apoptosis and autophagy pathways. Silybum marianum essential oils were studied alone and in combination with 5-FU in the HepG2 cell-line. The expression of NF-κB and Wnt signaling pathway genes as well as angiogenesis-, apoptosis- and autophagy-associated genes and proteins were evaluated using Western blot and qRT-PCR techniques. Each treatment decreased the viability of HepG2 cells compared with the control group. Moreover, S. marianum essential oils from Khozestan or Isfahan (Sm-K and Sm-I) in combination with 5-FU reduced the migration and invasion of HepG2 cells. Angiogenesis-related proteins i.e. VEGF, COX-2, Bfgf and HIF-1α were significantly reduced. Apoptosis- and autophagy-related proteins i.e. caspase-8, Bax, Bcl-2, Beclin-1, LC3-I, and LC3-II were modulated by each treatment. Each treatment decreased total NF κB (p65) and phospho NF κB (p65) at protein levels. The expression levels of Wnt pathway-related genes were also decreased. Taken together, these findings revealed that S. marianum, either alone or in combination with 5-Fu, could exert anti-tumor effects via modulating autophagy, apoptosis, angiogenesis, NF κB and Wnt signaling pathways.

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