| Popis: |
Hepatocellular carcinoma (HCC) is the most widespread primary liver cancer, with a projected prevalence of more than 1 million cases by 2025. HCC severely affects the entire human population and continues to be a serious global challenge. There is an urgent need for novel therapies to treat and prevent this potentially fatal disease. Bidens pilosa and Trianthema portulacastrum are noteworthy weeds that include a series of bioactive flavonoid constituents, hence, they can be utilized as potential health supplements and readily available sources of natural antioxidants, as well as effective constituents in medicinal applications. The current study aims to examine the efficiency of B. pilosa and T. portulacastrum extracts against HCC using the HepG2 cell line. B. pilosa and T. portulacastrum fresh leaf extracts were prepared using dimethyl sulfoxide. The obtained extracts were evaluated for their cytotoxic activity and potential CC50 using the MTT assay in HepG2 cell lines and normal cells. The relative messenger RNA (mRNA) of RAF-1, MEK-1, LC3B, and Atg12 genes was quantified using quantitative reverse-transcription polymerase chain reaction to detect the expression levels of autophagy-related genes in HepG2 cells in-vitro for HCC activity. Additionally, an ELISA assay was carried out for the quantification analysis of the released interleukin-1beta (IL-1β) and interleukin-1alpha (IL-1α). B. pilosa extract's cytotoxic activity confirmed its potential action on HepG2 cell lines upon treatment compared with normal cells. It was assessed for cytotoxicity using molecular studies against both RAF-1 and MEK-1 as proposed anticancer mechanisms and showed promising inhibitory activity against RAF-1 and MEK-1 gene expression. The ELISA assay revealed a substantial elevation of the proinflammatory cytokines IL-1α and IL-1β upon treatment. This study found that B. pilosa extract had potential inhibitory activities against both RAF-1 and MEK-1 gene expression, and a significant reduction in the relative expression of both LC3B and Atg12 genes upon treatment, without any detectable cytotoxic effects. This extract caused highly significant suppression of the Ras/Raf/MEK/ERK signaling pathway of tumor proliferation and induced an apoptotic signaling pathway. Hence, it could provide a lead structure for drug development strategies against hepatocellular carcinoma to be used in pharmaceutical preparations. |
