title: Growth inhibition of human gynecologic and colon cancer cells by Phyllanthus watsonii through apoptosis induction.
abstract: 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.
authors.affiliation: Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia. sujatha@um.edu.my
authors.forename: Sujatha
authors.initials: S
authors.lastname: Ramasamy
authors.forename: Norhanom
authors.initials: N
authors.lastname: Abdul Wahab
authors.forename: Nurhayati
authors.initials: N
authors.lastname: Zainal Abidin
authors.forename: Sugumaran
authors.initials: S
authors.lastname: Manickam
authors.forename: Zubaidah
authors.initials: Z
authors.lastname: Zakaria
mesh_terms: D000085:Acetates / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005591:Chemical Fractionation; D003110:Colonic Neoplasms; D053938:DNA Fragmentation; D004610:Ellagic Acid / Q000737:chemistry; D005260:Female; D006586:Hexanes / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D000432:Methanol / Q000737:chemistry; D029803:Phyllanthus / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D002583:Uterine Cervical Neoplasms
chemical_list: D000085:Acetates; D000970:Antineoplastic Agents; D006586:Hexanes; D010936:Plant Extracts; D012997:Solvents; D004610:Ellagic Acid; C007650:ethyl acetate; C505407:CASP3 protein, human; D053148:Caspase 3; D000432:Methanol