title: Physalin A induces apoptotic cell death and protective autophagy in HT1080 human fibrosarcoma cells.
abstract: Physalin A (1) is a withanolide isolated from Physalis alkekengi var. franchetii. In this study, the selective growth inhibitory effects on tumor cells induced by 1 were screened, and the mechanism was investigated on 1-induced growth inhibition, including apoptosis and autophagy, in human fibrosarcoma HT1080 cells. Apoptosis induced by 1 in HT1080 cells was associated with up-regulation of caspase-3 and caspase-8 expression. However, there were no significant changes in caspase-9, Bid, Bax, and Bcl-2 expression, indicating that 1-induced apoptosis in HT1080 cells occurs mainly through activation of the death receptor-associated extrinsic apoptotic pathways. Autophagy induced by 1 was found to antagonize apoptosis in HT1080 cells. This effect was enhanced by rapamycin and suppressed by the autophagy inhibitor 3-methyladenine (3MA). Loss of beclin 1 (as an autophagic regulator) function led to similar results to 3MA. However, 1 did not show inhibitory effects on normal human cells (human peripheral blood mononuclear cells). Taken together, these results suggest that 1 may be a promising agent for the treatment of cancer.
authors: Department of Natural Products Chemistry, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, People's Republic of China.
authors: Hao
authors: H
authors: He
authors: Ling-He
authors: LH
authors: Zang
authors: Yong-Sheng
authors: YS
authors: Feng
authors: Jian
authors: J
authors: Wang
authors: Wei-Wei
authors: WW
authors: Liu
authors: Li-Xia
authors: LX
authors: Chen
authors: Ning
authors: N
authors: Kang
authors: Shin-ichi
authors: S
authors: Tashiro
authors: Satoshi
authors: S
authors: Onodera
authors: Feng
authors: F
authors: Qiu
authors: Takashi
authors: T
authors: Ikejima
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008565:Membrane Proteins / Q000187:drug effects; D015394:Molecular Structure; D032321:Physalis / Q000737:chemistry*; D054358:Withanolides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D054358:Withanolides; C574201:physalin A