Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/113636
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dc.titleRole of intracellular thiol depletion, mitochondrial dysfunction and reactive oxygen species in Salvia Miltiorrhiza-induced apoptosis in human hepatoma HepG2 cells
dc.contributor.authorLiu, J.
dc.contributor.authorShen, H.M.
dc.contributor.authorOng, C.N.
dc.date.accessioned2014-12-01T06:56:44Z
dc.date.available2014-12-01T06:56:44Z
dc.date.issued2001-09-07
dc.identifier.citationLiu, J., Shen, H.M., Ong, C.N. (2001-09-07). Role of intracellular thiol depletion, mitochondrial dysfunction and reactive oxygen species in Salvia Miltiorrhiza-induced apoptosis in human hepatoma HepG2 cells. Life Sciences 69 (16) : 1833-1850. ScholarBank@NUS Repository.
dc.identifier.issn00243205
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/113636
dc.description.abstractRecent studies have demonstrated that induction of apoptosis is related to the cell growth inhibition potential of Salvia Miltiorrhiza (SM), a traditional herbal medicine. In the present study, we further explore the mechanistic pathway involved in SM-induced apoptosis in human hepatoma HepG2 cells. A rapid decline of intracellular glutathione (GSH) and protein thiol content was found in SM-treated cells. Moreover, SM exposure resulted in mitochondrial dysfunction as demonstrated by: (i) the onset of mitochondrial permeability transition (MPT); (ii) the disruption of mitochondrial membrane potential (MMP); and (iii) the release of cytochrome c from mitochondria into the cytosol. Subsequently, elevated level of intracellular reactive oxygen species (ROS) was observed prior to the onset of DNA fragmentation. However, no caspase-3 cleavage was observed throughout the whole period of SM treatment, while a caspase-3-independent poly(ADP-ribose) polymerase (PARP) cleavage was noted at the late stage in SM-induced apoptosis. Pretreatment of cells with N-acetylcysteine (NAC), the GSH synthesis precursor, conferred complete protection against MMP loss, ROS generation and apoptosis induced by SM. MPT inhibitors, cyclosporin A plus trifluoperazine, partially restored intracellular GSH content, and reduced SM-induced ROS formation and subsequently inhibited cell death. Moreover, antioxidants NAC, deferoxamine and catalase had little effect on GSH depletion and mitochondrial dysfunction, yet still were able to completely protect cells from SM-induced apoptosis. Taken together, our results suggest that SM deplete intracellular thiols, which, in turn, causes MPT and subsequent increase in ROS generation, and eventually apoptotic cell death. © 2001 Elsevier Science Inc. All rights reserved.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1016/S0024-3205(01)01267-X
dc.sourceScopus
dc.subjectApoptosis
dc.subjectCaspase-3
dc.subjectCytochrome c
dc.subjectGSH
dc.subjectMMP
dc.subjectMPT
dc.subjectProtein thiol
dc.subjectROS
dc.typeArticle
dc.contributor.departmentCOMMUNITY,OCCUPATIONAL & FAMILY MEDICINE
dc.description.sourcetitleLife Sciences
dc.description.volume69
dc.description.issue16
dc.description.page1833-1850
dc.description.codenLIFSA
dc.identifier.isiut000171016400001
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