Abstract
Ajwa dates (Phoenix dactylifera L.) are used by traditional therapeutic practitioners for several health benefits but most remain to be scientifically validated. In this study, we evaluated the apoptosis-inducing effect of ethanolic extract of Ajwa date pulp (ADP) on human hepatocellular carcinoma (HCC) HepG2 cells. High performance liquid chromatography analysis revealed the presence of polysaccharide β-D-glucan in ADP extract. Treated HCC cells revealed morphological characteristics of apoptosis under phase contrast microscopy. MTT assay demonstrated significant (p < 0.05) dose- and time-dependent inhibition of HCC cell growth. HCC cells were found to be in late apoptotic stage on treatment with higher doses of ADP extract as depicted by acridine orange/ethidium bromide and Annexin V-FITC/PI double stain. Importantly, ADP extract increased the reactive oxygen species level and decreased the mitochondrial membrane potential in treated HCC cells. Flow cytometry analysis demonstrated that ADP extract induced elevation of S and G2/M phases of cell cycle. Moreover, ADP extract induced apoptosis in HCC cells independent of tumor suppressor genes viz. CHEK2, ATM and TP53. Interestingly, ADP extract did not display any significant effect on normal cell line Vero. This study provides validation that ADP extract can be considered as a safe and natural potential drug candidate against human liver cancer.
Highlights
Various treatment strategies based on hepatic resection, orthotopic liver transplantation, chemo-embolization and systemic chemotherapies[6], are available
The present study undertook the unprecedented investigation of cytotoxicity and underlying mechanism of apoptotic cell death induced by Ajwa date pulp (ADP) extract on human hepatocellular carcinoma (HCC) HepG2 cells
This study examined the active component of ADP extract, which may have a potential role in causing cytotoxicity
Summary
Various treatment strategies based on hepatic resection, orthotopic liver transplantation, chemo-embolization and systemic chemotherapies[6], are available. Drug resistance and side-effects of liver failure accompanying the disease limit the successful outcome in most cases[7]. In this context, natural products may be considered as safe and effective alternative therapeutic methods for the treatment of HCC and it is essential to rigorously explore novel natural products that effectively cure HCC patients. Natural products are primary sources of effective anticancer drugs with novel structures and unique mechanisms of action for the treatment of various forms of cancer[9]. A previous study has reported that the aqueous extract of Ajwa dates inhibits diethylnitrosamine-induced liver carcinoma in a rat model[17]. The present study describes the effects of Ajwa dates against HCC cells. The present study makes significant contributions to the field of natural-product based therapeutics in cancer
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