Abstract
BackgroundCancer is a leading cause of death accounting for 15-20% of global mortality. Although advancements in diagnostic and therapeutic technologies have improved cancer survival statistics, 75% of the world population live in underdeveloped regions and have poor access to the advanced medical remedies. Natural therapies hence become an alternative choice of treatment. Ashwagandha, a tropical herb used in Indian Ayurvedic medicine, has a long history of its health promoting and therapeutic effects. In the present study, we have investigated an anticancer activity in the water extract of Ashwagandha leaves (ASH-WEX).Methodology/Principal FindingsAnticancer activity in the water extract of Ashwagandha leaves (ASH-WEX) was detected by in vitro and in vivo assays. Bioactivity-based size fractionation and NMR analysis were performed to identify the active anticancer component(s). Mechanism of anticancer activity in the extract and its purified component was investigated by biochemical assays. We report that the ASH-WEX is cytotoxic to cancer cells selectively, and causes tumor suppression in vivo. Its active anticancer component was identified as triethylene glycol (TEG). Molecular analysis revealed activation of tumor suppressor proteins p53 and pRB by ASH-WEX and TEG in cancer cells. In contrast to the hypophosphorylation of pRB, decrease in cyclin B1 and increase in cyclin D1 in ASH-WEX and TEG-treated cancer cells (undergoing growth arrest), normal cells showed increase in pRB phosphorylation and cyclin B1, and decrease in cyclin D1 (signifying their cell cycle progression). We also found that the MMP-3 and MMP-9 that regulate metastasis were down regulated in ASH-WEX and TEG-treated cancer cells; normal cells remained unaffected.ConclusionWe provide the first molecular evidence that the ASH-WEX and TEG have selective cancer cell growth arrest activity and hence may offer natural and economic resources for anticancer medicine.
Highlights
Cancer defines a large group of diseases originating from uncontrolled cell division in any part of the body
And 1C, the treatment of normal and cancer cells with serial doses of ASH-WEX revealed its cytotoxicity to human cancer cells at doses 0.8% and above; normal human cells (MRC5, TIG-1 and WI-38) remained unaffected (Figure 1A-C). These findings suggested that the ASH-WSX has selective cancer cell killing activity, very similar to the alcoholic extract of Ashwagandha leaves [38]
Since the anticancer activity in water extract could be extremely beneficial for human consumption, we extended the study to examine the (i) toxicity assays in mice and (ii) in vivo anti-tumor test in nude mice subcutaneous xenograft and tail vein metastasis models
Summary
Cancer defines a large group of diseases originating from uncontrolled cell division in any part of the body. The present study was designed to investigate the effect of water extract of Ashwagandha leaves (ASH-WEX) on normal and cancer cell proliferation. Oral feeding of TEG, similar to ASH-WEX (as described above), to the mice implanted with HT1080 subcutaneous xenograft and tail vein injections showed slow tumor growth as compared to the control mice suggesting tumor suppressive activity in TEG (Figures 5A and 5B).
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