title: Induction of p53-independent growth inhibition in lung carcinoma cell A549 by gypenosides.
abstract: The objectives of this study are to investigate antiproliferative effect and mechanisms of bioactive compounds from Gynostemma pentaphyllum (G. pentaphyllum) on lung carcinoma cell A549. Saponins, carotenoids and chlorophylls were extracted and fractionated by column chromatography, and were subjected to high-performance liquid chromatography-mass spectrometry analyses. The saponin fraction, which consisted mainly of gypenoside (Gyp) XXII and XXIII, rather than the carotenoid and chlorophyll ones, was effective in inhibiting A549 cell growth in a concentration- and a time-dependent manner as evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The estimated half maximal inhibitory concentration (IC50 ) of Gyp on A549 cells was 30.6 μg/ml. Gyp was further demonstrated to induce an apparent arrest of the A549 cell cycle at both the S phase and the G2/M phase, accompanied by a concentration- and a time-dependent increase in the proportions of both the early and late apoptotic cells. Furthermore, Gyp down-regulated cellular expression of cyclin A and B as well as BCL-2, while up-regulated the expression of BAX, DNA degradation factor 35 KD, poly [ADP-ribose] polymerase 1, p53, p21 and caspase-3. Nevertheless, both the treatment of a p53 inhibitor, pifithrin-α, and the small hairpin RNA-mediated p53 knockdown in the A549 cells did not alter the growth inhibition effect induced by Gyp. As a result, the cell cycle arrest and apoptosis of A549 cells induced by Gyp would most likely proceed through p53-independent pathway(s).
authors.affiliation: School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.|Department of Surgery, Cathay General Hospital, Taipei, Taiwan.
authors.forename: Jung-Sen
authors.initials: JS
authors.lastname: Liu
authors.affiliation: Graduate Institute of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Tzu-Hsuan
authors.initials: TH
authors.lastname: Chiang
authors.affiliation: School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Jinn-Shyan
authors.initials: JS
authors.lastname: Wang
authors.affiliation: School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Li-Ju
authors.initials: LJ
authors.lastname: Lin
authors.affiliation: School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Wei-Chih
authors.initials: WC
authors.lastname: Chao
authors.affiliation: Department of Food Science, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Baskaran Stephen
authors.initials: BS
authors.lastname: Inbaraj
authors.affiliation: School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Jyh-Feng
authors.initials: JF
authors.lastname: Lu
authors.affiliation: Department of Food Science, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Bing-Huei
authors.initials: BH
authors.lastname: Chen
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002338:Carotenoids / Q000032:analysis; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002734:Chlorophyll / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D005434:Flow Cytometry; D029774:Gynostemma / Q000737:chemistry; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D013058:Mass Spectrometry; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D012503:Saponins / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D017304:Annexin A5; D010936:Plant Extracts; D012503:Saponins; D016159:Tumor Suppressor Protein p53; C474918:gypenoside; D002734:Chlorophyll; D002338:Carotenoids
keywords: Gynostemma pentaphyllum; carotenoid; chlorophyll; lung cancer cell; saponin