BackgroundHouttuynia cordata Thunb. and Phyllanthus emblica Linn. are native plants with medicinal and nutritive significance in Asia. The present study was aimed at evaluating antiproliferative effects on human cancer cell lines and identifying the phenolic acid composition of water and ethanolic extracts of the powdered formula of H. cordata fermented broth and P. emblica fruit.MethodsAnticancer activity of the extracts was evaluated against HeLa, HT29, HCT116, MCF7 and Jurkat cells using an MTT assay and flow cytometric analysis of apoptosis induction and cell cycle arrest. Reverse phase HPLC was exploited for identification and quantification of some phenolic acids.ResultsMTT assay showed that both water and ethanolic extracts significantly decreased the viability of cancer cells in a dose- and time-dependent fashion. Based on the IC50 values, ethanolic extract (IC50 values = 0.12–0.65 mg/mL) was more cytotoxic than water extract (IC50 values = 0.22–0.85 mg/mL) and Jurkat cells were the most sensitive to both extracts (IC50 values = 0.12–0.69 mg/mL). The underlying mechanism for antiproliferative activity was apoptosis induction, especially in HT29, HCT116, MCF7 and Jurkat cells. HT29 cells were the most sensitive to extract-induced apoptosis. Ethanolic extract was more effective at inducing apoptosis than water extract. Moreover, cell cycle arrest was found to be another mechanism behind growth inhibition in Jurkat and HCT116 cells. However, these extracts were relatively less toxic to non-cancer Vero cells. HPLC analysis demonstrated that the powder mix extracts contained seven identified phenolic acids namely gallic, p-hydroxybenzoic, vanillic, syringic, p-coumaric, ferulic and sinapinic acids, where p-coumaric acid was detected in the highest concentration followed by ferulic acid.ConclusionOverall, the results of this study suggest the powdered formula of H. cordata fermented broth and P. emblica fruit as an alternative medicine for cancer prevention and treatment.
Peanut phenolics appear to influence the extent of histone acetylation in MCF-7 and HeLa cells, and this activity modulates multiple pathways that are implicated in cancer prevention.
Phenolic compounds present in our diet play an important role in colon cancer chemoprevention. Previous results demonstrated that peanut testa extract inhibited both histone deacetylase (HDAC) activity and the growth of colon cancer cells. In this study, four identified phenolic compounds in peanut testae (resveratrol, p-coumaric acid, ferulic acid, and sinapinic acid) were investigated for their HDAC inhibitory and anticancer activities against colon cancer cell lines. In vitro study revealed that resveratrol exhibited the greatest HDAC inhibitory activity. Molecular docking studies demonstrated that all four compounds could bind both HDAC1 and HDAC2. Resveratrol exhibited the most effective antiproliferative activity against both human colon adenocarcinoma (HT29) and human colorectal carcinoma (HCT116) cells. Apoptosis induction by ferulic acid and resveratrol appeared to be associated with p53 activation in HCT116 cells. However, resveratrol, p-coumaric acid, ferulic acid, and sinapinic acid induced apoptosis of HT29 cells in a p53-independent manner. Low-concentration treatments of p-coumaric and ferulic acids resulted in cell cycle arrest of HCT116 cells. In contrast, high-concentration treatments of p-coumaric and ferulic acids showed cell death activation as evidenced by increased sub-G1 fractions. The induction of p21 by p-coumaric acid and resveratrol correlated well with the decreased CDK4 levels and cell cycle arrest. Resveratrol, p-coumaric acid, ferulic acid, and sinapinic acid caused activation of pERK1/2 in HCT116 cells, whereas ferulic and sinapinic acids caused downregulation of pERK1/2 in HT29 cells. These results suggest that these peanut phenolics may be potential antineoplastic agents for colon cancer chemoprevention/chemotherapy.
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