Silybum marianum total extract, silymarin and silibinin abate hepatocarcinogenesis and hepatocellular carcinoma growth via modulation of the HGF/c-Met, Wnt/β-catenin, and PI3K/Akt/mTOR signaling pathways

Hepatocellular carcinoma (HCC) has been identified as one of the most deadly malignancies with limited therapeutic efficacy worldwide. However, understanding the molecular mechanisms of crosstalk between signaling pathways in HCC and predicting cancer cell responses to targeted therapeutic intervent...

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Autores principales:	Nour Y.S. Yassin, Sameh F. AbouZid, Asmaa M. El-Kalaawy, Tarek M. Ali, Mazen M. Almehmadi, Osama M. Ahmed
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Hepatocellular carcinoma Silybum marianum Wnt/β-catenin HGF/c-Met PI3K/Akt/mTOR pathways Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/efcee6704f5947968d9be9721217a27c
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spelling	oai:doaj.org-article:efcee6704f5947968d9be9721217a27c2021-11-14T04:30:32ZSilybum marianum total extract, silymarin and silibinin abate hepatocarcinogenesis and hepatocellular carcinoma growth via modulation of the HGF/c-Met, Wnt/β-catenin, and PI3K/Akt/mTOR signaling pathways0753-332210.1016/j.biopha.2021.112409https://doaj.org/article/efcee6704f5947968d9be9721217a27c2022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221011951https://doaj.org/toc/0753-3322Hepatocellular carcinoma (HCC) has been identified as one of the most deadly malignancies with limited therapeutic efficacy worldwide. However, understanding the molecular mechanisms of crosstalk between signaling pathways in HCC and predicting cancer cell responses to targeted therapeutic interventions remain to be challenge. Thus, in this study, we aimed to evaluate the anticancerous efficacy of Silybum marianum total extract (STE), silymarin (Sm), and silibinin (Sb) against experimentally-induced HCC in rats. In vitro investigations were also performed and the anticancer effects against HCC cell lines (HepG2 and Huh7) were confirmed. Wistar rats were given diethylnitrosamine (DEN)/2-acetylaminofluorene (AAF)/carbon tetrachloride (CCl4) and were orally treated with STE (200 mg/kg body weight (bw)), Sm (150 mg/kg bw), and Sb (5 mg/kg bw) every other day from the 1st or 16th week to the 25th week of DEN/AAF/CCl4 injection. Treatment with STE, Sm, and Sb inhibited the growth of cancerous lesions in DEN/AAF/CCl4-treated rats. This inhibition was associated with inhibition of Ki-67 expression and repression of HGF/cMet, Wnt/β-catenin, and PI3K/Akt/mTOR signaling pathways. STE, Sm, and Sb improved liver function biomarkers and tumor markers (AFP, CEA, and CA19.9) and increased total protein and albumin levels in serum. STE, Sm, and Sb treatment was also noted to reduce the hepatic production of lipid peroxides, increase hepatic glutathione content, and induce the activities of hepatic antioxidant enzymes in DEN/AAF/CCl4-treated rats. These results indicate that STE, Sm, and Sb exert anti-HCC effects through multiple pathways, including suppression of Ki-67 expression and HGF/cMet, Wnt/β-catenin, and PI3K/Akt/mTOR pathways and enhancement of antioxidant defense mechanisms.Nour Y.S. YassinSameh F. AbouZidAsmaa M. El-KalaawyTarek M. AliMazen M. AlmehmadiOsama M. AhmedElsevierarticleHepatocellular carcinomaSilybum marianumWnt/β-cateninHGF/c-MetPI3K/Akt/mTOR pathwaysTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 145, Iss , Pp 112409- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Hepatocellular carcinoma Silybum marianum Wnt/β-catenin HGF/c-Met PI3K/Akt/mTOR pathways Therapeutics. Pharmacology RM1-950
spellingShingle	Hepatocellular carcinoma Silybum marianum Wnt/β-catenin HGF/c-Met PI3K/Akt/mTOR pathways Therapeutics. Pharmacology RM1-950 Nour Y.S. Yassin Sameh F. AbouZid Asmaa M. El-Kalaawy Tarek M. Ali Mazen M. Almehmadi Osama M. Ahmed Silybum marianum total extract, silymarin and silibinin abate hepatocarcinogenesis and hepatocellular carcinoma growth via modulation of the HGF/c-Met, Wnt/β-catenin, and PI3K/Akt/mTOR signaling pathways
description	Hepatocellular carcinoma (HCC) has been identified as one of the most deadly malignancies with limited therapeutic efficacy worldwide. However, understanding the molecular mechanisms of crosstalk between signaling pathways in HCC and predicting cancer cell responses to targeted therapeutic interventions remain to be challenge. Thus, in this study, we aimed to evaluate the anticancerous efficacy of Silybum marianum total extract (STE), silymarin (Sm), and silibinin (Sb) against experimentally-induced HCC in rats. In vitro investigations were also performed and the anticancer effects against HCC cell lines (HepG2 and Huh7) were confirmed. Wistar rats were given diethylnitrosamine (DEN)/2-acetylaminofluorene (AAF)/carbon tetrachloride (CCl4) and were orally treated with STE (200 mg/kg body weight (bw)), Sm (150 mg/kg bw), and Sb (5 mg/kg bw) every other day from the 1st or 16th week to the 25th week of DEN/AAF/CCl4 injection. Treatment with STE, Sm, and Sb inhibited the growth of cancerous lesions in DEN/AAF/CCl4-treated rats. This inhibition was associated with inhibition of Ki-67 expression and repression of HGF/cMet, Wnt/β-catenin, and PI3K/Akt/mTOR signaling pathways. STE, Sm, and Sb improved liver function biomarkers and tumor markers (AFP, CEA, and CA19.9) and increased total protein and albumin levels in serum. STE, Sm, and Sb treatment was also noted to reduce the hepatic production of lipid peroxides, increase hepatic glutathione content, and induce the activities of hepatic antioxidant enzymes in DEN/AAF/CCl4-treated rats. These results indicate that STE, Sm, and Sb exert anti-HCC effects through multiple pathways, including suppression of Ki-67 expression and HGF/cMet, Wnt/β-catenin, and PI3K/Akt/mTOR pathways and enhancement of antioxidant defense mechanisms.
format	article
author	Nour Y.S. Yassin Sameh F. AbouZid Asmaa M. El-Kalaawy Tarek M. Ali Mazen M. Almehmadi Osama M. Ahmed
author_facet	Nour Y.S. Yassin Sameh F. AbouZid Asmaa M. El-Kalaawy Tarek M. Ali Mazen M. Almehmadi Osama M. Ahmed
author_sort	Nour Y.S. Yassin
title	Silybum marianum total extract, silymarin and silibinin abate hepatocarcinogenesis and hepatocellular carcinoma growth via modulation of the HGF/c-Met, Wnt/β-catenin, and PI3K/Akt/mTOR signaling pathways
title_short	Silybum marianum total extract, silymarin and silibinin abate hepatocarcinogenesis and hepatocellular carcinoma growth via modulation of the HGF/c-Met, Wnt/β-catenin, and PI3K/Akt/mTOR signaling pathways
title_full	Silybum marianum total extract, silymarin and silibinin abate hepatocarcinogenesis and hepatocellular carcinoma growth via modulation of the HGF/c-Met, Wnt/β-catenin, and PI3K/Akt/mTOR signaling pathways
title_fullStr	Silybum marianum total extract, silymarin and silibinin abate hepatocarcinogenesis and hepatocellular carcinoma growth via modulation of the HGF/c-Met, Wnt/β-catenin, and PI3K/Akt/mTOR signaling pathways
title_full_unstemmed	Silybum marianum total extract, silymarin and silibinin abate hepatocarcinogenesis and hepatocellular carcinoma growth via modulation of the HGF/c-Met, Wnt/β-catenin, and PI3K/Akt/mTOR signaling pathways
title_sort	silybum marianum total extract, silymarin and silibinin abate hepatocarcinogenesis and hepatocellular carcinoma growth via modulation of the hgf/c-met, wnt/β-catenin, and pi3k/akt/mtor signaling pathways
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/efcee6704f5947968d9be9721217a27c
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Silybum marianum total extract, silymarin and silibinin abate hepatocarcinogenesis and hepatocellular carcinoma growth via modulation of the HGF/c-Met, Wnt/β-catenin, and PI3K/Akt/mTOR signaling pathways

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