Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the greatest cause of cancer-related death in the world. Garden cress (Lepidium sativum) seeds have been proven to possess extraordinary antioxidant, anti-inflammatory, hypothermic, and analgesic properties. In this study, in vitro cytotoxic efficiency evaluation of L. sativum fractions was performed against two hepatocellular carcinoma cell lines (HuH-7 and HEPG-2), and the expression of some apoptotic genes was explored. In addition, the chemical composition of a potent extract of L. sativum was analyzed using gas chromatography coupled with mass spectrometry. Then, molecular docking analysis was implemented to identify the potential targets of the L. sativum components’ most potent extract. Overall, the n-hexane extract was the most potent against the two HCC cell lines. Moreover, these cytotoxicity levels were supported by the significant downregulation of EGFR and BCL2 gene expression levels and the upregulation of SMAD3, BAX, and P53 expression levels in both HuH-7 and HEPG2 cell lines. Regarding L. sativum’s chemical composition, GC–MS analysis of the n-hexane extract led to the identification of thirty compounds, including, mainly, hydrocarbons and terpenoids, as well as other volatile compounds. Furthermore, the binding affinities and interactions of the n-hexane fraction’s major metabolites were predicted against EGFR and BCL2 molecular targets using the molecular docking technique. These findings reveal the potential use of L. Sativum in the management of HCC.
Highlights
IntroductionLiver cancer is the second highest cause of cancer-related mortality worldwide
The current results revealed that the expression level of TGF-β was upregulated upon treatment with the n-hexane extract of L. sativum in the HEPG2 cell line, with a fold change of 2.1 ± 0.1, and it was upregulated in the HuH-7 cell line by 1.7 ± 0.1 fold
The current study showed a concentration-dependent cytotoxic effect of methylene chloride (47 ug/mL), ethyl acetate (63.8 ug/mL), and n-hexane (45 ug/mL) extracts on HEPG2 cells, while on HuH-7 cells, methylene chloride (59 ug/mL), ethyl acetate ug/mL), and n-hexane (59.3 ug/mL) from L. sativum extracts were compared to a non- 276 (63.5 ug/mL), and n-hexane (59.3 ug/mL) from L. sativum extracts were compared to a treated control
Summary
Liver cancer is the second highest cause of cancer-related mortality worldwide. HCC is estimated to be the sixth most prevalent type of cancer worldwide; in Egypt, it represents the fourth most widespread cancer [2]. The prevalence of HCC is rising dramatically, especially in Africa and Asia. In Egypt, health officials consider HCC the most critical health problem. Chronic HBV (Hepatitis B Virus) infection, autoimmune hepatitis, chronic alcohol use, obesity, diabetes mellitus, and hepatitis C virus (HCV) sequelae are all risk factors for HCC in Egypt [4]. Extensive attempts have been made to resolve this problem through the development of novel treatments that can replace the current conventional therapies, such as chemotherapy, which is still the primary approach used to treat liver cancer [5]
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