title: Natural plant extract tubeimoside I promotes apoptosis-mediated cell death in cultured human hepatoma (HepG2) cells.
abstract: Tubeimoside I (TBMS I), an extract from Chinese herbal medicine Bolbostemma paniculatum (MAXIM.) FRANQUET (Cucurbitaceae) has been shown as a potent anti-tumor agent for a variety of human cancers, but yet to be evaluated for hepatoma that is highly prevalent in Eastern Asian countries including China. Here, we examined in vitro the cytotoxic effects of TBMS I on human hepatoma (HepG2) and normal liver (L-02) cell lines. We also investigated TBMS I-induced molecular events related to apoptosis in HepG2 cells. The results show that TBMS I inhibited the proliferation of both HepG2 and L-02 cells in a dose- and time-dependent manner, but HepG2 cells appeared more sensitive to the agent. When exposed to TBMS I for 24, 48 and 72 h, IC₅₀ for HepG2 cells versus L-02 cells were 15.5 vs. 23.1, 11.7 vs. 16.2, 9.2 vs. 13.1 (µM, p<0.01), respectively. TBMS I induced cell shrinkage, nuclear condensation and fragmentation, cell cycle arrest at the G2/M phase, mitochondrial membrane disruption, release of cytochrome c from the mitochondria, activation of caspase 3 and 9, and shifting Bax/Bcl-2 ratio from being anti-apoptotic to pro-apoptotic, all indicative of initiation and progression of apoptosis involving mitochondrial dysfunction. Taken together, these results indicate for the first time that TBMS I potently inhibited growth in HepG2 cells by mediating a cascade of apoptosis signaling pathways. Considering its sensitivity of HepG2 cells, preferential distribution in the liver and natural product origin, TBMS I therefore may have a great potential as a chemotherapeutic drug candidate for hepatoma.
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, and Bioengineering College, Chongqing University, Chongqing, China.
authors.forename: Yashu
authors.initials: Y
authors.lastname: Wang
authors.forename: Linhong
authors.initials: L
authors.lastname: Deng
authors.forename: Hongzhe
authors.initials: H
authors.lastname: Zhong
authors.forename: Yajie
authors.initials: Y
authors.lastname: Wang
authors.forename: Xuemei
authors.initials: X
authors.lastname: Jiang
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D053144:Cell Nucleus Shape / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D004365:Drugs, Chinese Herbal; D012503:Saponins; D014315:Triterpenes; C051084:tubeimoside I