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Ursolic Acid Induces Apoptosis Through Mitochondrial Intrinsic Pathway and Suppression of ERK1/2 MAPK in HeLa Cells
Li, Yanhong; Lu, Xueying; Qi, Hongxue; Li, Xiaobo; Xiao, Xiangwen; Gao, Jianfeng
2014
Source PublicationJOURNAL OF PHARMACOLOGICAL SCIENCES
ISSN1347-8613
Volume125Issue:2Pages:202-210
AbstractUrsolic acid (UA), a natural pentacyclic triterpenoid compound, has been demonstrated to induce apoptosis in various tumors. The aim of the present study was to elucidate the molecular mechanisms of UA-induced apoptosis in HeLa cells. Here, we reported that UA induced apoptosis through the mitochondrial intrinsic pathway in HeLa cells, as shown by release of cytosol cytochrome c, activation of caspase-9 and -3, reduction of Bcl-2 and Bcl-xL, and increase of Bax and Bak. UA down-regulated the phosphorylation of ERK1/2 and p38, whereas phosphorylation of INK was unchanged. The roles of ERK1/2 and p38 were further confirmed using the ERK1/2 inhibitor (U0126) and p38 inhibitor (SB203580). U0126 markedly increased UA-induced the Bax/Bcl-2 ratio, the increase of cytosol cytochrome c, and the levels of cleaved caspase-3, but SB203580 had little effects on the above characters, suggesting the ERK1/2 signaling pathway is required for apoptosis. Furthermore, UA up-regulated DUSP 1, 2, 4, 5, 6, 7, 9, and 10 mRNA expressions, which may be a clue for the role of dephosphorylation of ERK1/2 and p38. These data suggested that the apoptotic mechanism of UA treatment in HeLa cells was through the mitochondrial intrinsic pathway and closely associated with the suppression of the ERK1/2 signaling pathway.
KeywordUrsolic Acid Apoptosis Hela Cell Mitogen-activated Protein Kinase (Mapk) Dual-specific Phosphatase (Dusp)
Funding OrganizationNatural Science Foundation of Xinjiang Uygur Autonomous Region;Western Action Project of Bureau of Resources and Environmental Science, Chinese Academy of Sciences, P. R. China ; Natural Science Foundation of Xinjiang Uygur Autonomous Region;Western Action Project of Bureau of Resources and Environmental Science, Chinese Academy of Sciences, P. R. China
DOI10.1254/jphs.14017FP
Indexed BySCI
Funding OrganizationNatural Science Foundation of Xinjiang Uygur Autonomous Region;Western Action Project of Bureau of Resources and Environmental Science, Chinese Academy of Sciences, P. R. China ; Natural Science Foundation of Xinjiang Uygur Autonomous Region;Western Action Project of Bureau of Resources and Environmental Science, Chinese Academy of Sciences, P. R. China
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Cited Times:29[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.xjipc.cas.cn/handle/365002/3777
Collection省部共建新疆特有药用资源利用重点实验室
AffiliationChinese Acad Sci, Xinjiang Tech Inst Phys & Chem, Key Lab Chem Plant Resources Arid Reg, Urumqi 830011, Peoples R China;Shihezi Univ, Coll Anim Sci & Technol, Shihezi 832003, Peoples R China;Xinjian Educ Inst, Dept Phys Educ, Urumqi 830043, Peoples R China
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Li, Yanhong,Lu, Xueying,Qi, Hongxue,et al. Ursolic Acid Induces Apoptosis Through Mitochondrial Intrinsic Pathway and Suppression of ERK1/2 MAPK in HeLa Cells[J]. JOURNAL OF PHARMACOLOGICAL SCIENCES,2014,125(2):202-210.
APA Li, Yanhong,Lu, Xueying,Qi, Hongxue,Li, Xiaobo,Xiao, Xiangwen,&Gao, Jianfeng.(2014).Ursolic Acid Induces Apoptosis Through Mitochondrial Intrinsic Pathway and Suppression of ERK1/2 MAPK in HeLa Cells.JOURNAL OF PHARMACOLOGICAL SCIENCES,125(2),202-210.
MLA Li, Yanhong,et al."Ursolic Acid Induces Apoptosis Through Mitochondrial Intrinsic Pathway and Suppression of ERK1/2 MAPK in HeLa Cells".JOURNAL OF PHARMACOLOGICAL SCIENCES 125.2(2014):202-210.
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