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Phyllanthus watsonii  Airy Shaw is an endemic plant found in Peninsular Malaysia. Although there are numerous reports on the anti cancer properties of other  Phyllanthus  species, published information on the cytotoxicity of  P. watsonii  are very limited. The present study was carried out with bioassay-guided fractionation approach to evaluate the cytotoxicity and apoptosis induction capability of the  P. watsonii  extracts and fractions on human gynecologic (SKOV-3 and Ca Ski) and colon (HT-29) cancer cells.  P. watsonii  extracts exhibited strong cytotoxicity on all the cancer cells studied with IC 50  values of ≤ 20.0 µg/mL. Hexane extract of  P. watsonii  was further subjected to bioassay-guided fractionation and yielded 10 fractions (PW-1→PW-10). PW-4→PW-8 portrayed stronger cytotoxic activity and was further subjected to bioassay-guided fractionation and resulted with 8 sub-fractions (PPWH-1→PPWH-8). PPWH-7 possessed greatest cytotoxicity (IC 50  values ranged from 0.66 – 0.83 µg/mL) and was selective on the cancer cells studied. LC-MS/MS analysis of PPWH-7 revealed the presence of ellagic acid, geranic acid, glochidone, betulin, phyllanthin and sterol glucoside. Marked morphological changes, ladder-like appearance of DNA and increment in caspase-3 activity indicating apoptosis were clearly observed in both human gynecologic and colon cancer cells treated with  P. watsonii  especially with PPWH-7. The study also indicated that  P. watsonii  extracts arrested cell cycle at different growth phases in SKOV-3, Ca Ski and HT-29 cells. Cytotoxic and apoptotic potential of the endemic  P. watsonii  was investigated for the first time by bioassay-guided approach. These results demonstrated that  P. watsonii  selectively inhibits the growth of SKOV-3, Ca Ski and HT-29 cells through apoptosis induction and cell cycle modulation. Hence,  P. watsonii  has the potential to be further exploited for the discovery and development of new anti cancer drugs.

Growth Inhibition of Human Gynecologic and Colon Cancer Cells by Phyllanthus watsonii through Apoptosis Induction