Supercritical carbon dioxide extract of Physalis peruviana induced cell cycle arrest and apoptosis in human lung cancer H661 cells.
Physalis peruviana L. (PP) is a popular folk medicine used for treating cancer, leukemia, hepatitis, rheumatism and other diseases. In this study, our objectives were to examine the total flavonoid and phenol content of different PP extracts (aqueous: HWEPP; ethanolic: EEPP; supercritical carbon dioxide: SCEPP-0, SCEPP-4 and SCEPP-5) and their antiproliferative effects in human lung cancer H661 cells. Among all the extracts tested, results showed that SCEPP-5 possessed the highest total flavonoid (226.19 +/- 4.15 mg/g) and phenol (100.82 +/- 6.25 mg/g) contents. SCEPP-5 also demonstrated the most potent inhibitory effect on H661 cell proliferation. Using DNA ladder and flow cytometry analysis, SCEPP-5 effectively induced H661 cell apoptosis as demonstrated by the accumulation of Sub-G1 peak and fragmentation of DNA. SCEPP-5 not only induced cell cycle arrest at S phase, it also up-regulated the expression of pro-apoptotic protein (Bax) and down-regulated the inhibitor of apoptosis protein (IAP). Furthermore, the apoptotic induction in H661 cells was found to associate with an elevated p53 protein expression, cytochrome c release, caspase-3 activation and PARP cleavage. Taken together, these results conclude that SCEPP-5 induced cell cycle arrest at S phase, and its apoptotic induction could be mediated through the p53-dependent pathway and modification of Bax and XIAP proteins expression. The results have also provided important pharmacological backgrounds for the potential use of PP supercritical fluid extract as products for cancer prevention.
Graduate Institute of Nutritional Health, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan.
Shu-Jing
SJ
Wu
Shun-Pang
SP
Chang
Doung-Liang
DL
Lin
Shyh-Shyan
SS
Wang
Fwu-Feuu
FF
Hou
Lean-Teik
LT
Ng
D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002245:Carbon Dioxide; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D025924:Chromatography, Supercritical Fluid; D053938:DNA Fragmentation / Q000187:drug effects; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification; D032321:Physalis / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; D007202:Indicators and Reagents; D010636:Phenols; D010936:Plant Extracts; D002245:Carbon Dioxide