Involvement of Mitochondrial Pathway in Triptolide-Induced Cytotoxicity in Human Normal Liver L-02 Cells

Yao, Jincheng; Jiang, Zhenzhou; Duan, Weigang; Huang, Jing-Feng; Zhang, Luyong; Hu, Ling; He, Ling; Fu, Li; Xiao, Yajie; Shu, Bin; Liu, Chunhui

doi:10.1248/bpb.31.592

Cited by 95 publications

(54 citation statements)

References 35 publications

(32 reference statements)

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“…Moreover, the elevated Bax expression and the lessened Bcl-2 and Bcl-X l expression further disclose that the initiation of the intrinsic pathway owes to the up-regulation of the Bax/ Bcl-2, -X l ratio. According to previous reports on triptolide's pro-apoptotic activity, in majority of cells, triptolide-induced cytotoxity is through the mitochondrial pathway (37,(42)(43)(44)(45)(46)(47). With regard to the mechanism how triptolide triggers the mitochondria-dependent pathway, some researchers consider that it attributes to the increasing level of Bax protein and the decreasing level of Bcl-2, -X l (38,47,48), which concord with our conclusion.…”

Section: Discussionsupporting

confidence: 89%

“…According to previous reports on triptolide's pro-apoptotic activity, in majority of cells, triptolide-induced cytotoxity is through the mitochondrial pathway (37,(42)(43)(44)(45)(46)(47). With regard to the mechanism how triptolide triggers the mitochondria-dependent pathway, some researchers consider that it attributes to the increasing level of Bax protein and the decreasing level of Bcl-2, -X l (38,47,48), which concord with our conclusion. the downregulation of X-linked inhibitor of apoptosis protein (XIAp) in AMl cells has also been reported (43).…”

Section: Discussionsupporting

confidence: 89%

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Triptolide-induced cell cycle arrest and apoptosis in human renal cell carcinoma cells

Zhu²,

Leng³

et al. 2011

Oncol Rep

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Abstract. renal cell carcinoma (rcc) is the most frequent type of renal-originated malignancy. Although nephrectomy is successfully used to save the lives of patients with localized rcc, treatment of advanced and other refractory rccs is poor and still inadequate. Here, we show that triptolide, a small molecule and a well-known anti-inflammatory and antiimmunity agent used in the clinic, is capable of inducing cell apoptosis via the mitochondrial pathway in the 786-0 rcc cell line. this induction occurred in concert with reduced expression of genes related to the stabilization of mitochondria such as Bcl-2 and Bcl-X l . cell cycle analysis showed that exposure to triptolide decreased the proportion of cells in the g0/g1 and g2/M phases, and increased the proportion of cells in the s phase. cell accumulation in the s phase can be attributed to reduced expression of cell cycle checkpoint regulators such as cyclin A, cyclin B, cDK1, cDK2 and retinoblastoma proteins (rb). these results raise the possibility that triptolide-induced apoptosis is mediated by cell cycle arrest. similarly, in another human rcc cell line, os-rc-2, triptolide-induced apoptosis and cell accumulation in s phase were also observed. therefore, triptolide emerges as a stimulator of apoptosis by influencing coordinate regulation of proliferation and apoptosis, and may be applicable to the treatment of human renal cell carcinoma.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 89%

Triptolide-induced cell cycle arrest and apoptosis in human renal cell carcinoma cells

Zhu²,

Leng³

et al. 2011

Oncol Rep

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“…One of its mechanisms of action is to trigger apoptosis, although a common problem with anti-cancer drugs is induction of programmed cell death in both normal and tumorous cells (Carter et al, 2006;Yao et al, 2008). Nonetheless, triptolide has potential not only as an anti-inflammatory, but, in its capacity as a downregulator of the JAK/STAT3 pathway, as an anti-cancer compound.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, clinical trials in China using triptolide have shown remission rates of 71% and 87% in mononucleocytic and granulocytic leukemia, respectively (Lu et al, 1992). Although the precise mechanism of its anti-cancer effects is unknown, triptolide has pro-apoptotic effects (Carter et al, 2006;Liang and Fu, 2008;Yao et al, 2008). triptolide ameliorates chronic colitis mediated by the acquired immune response in a mouse model (Wei et al, 2008), but no previous reports has examined the effect of triptolide on colon cancer induced by chronic colitis.…”

Section: Introductionmentioning

confidence: 99%

Triptolide downregulates Rac1 and the JAK/STAT3 pathway and inhibits colitis-related colon cancer progression

et al. 2009

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Triptolide, a diterpenoid triepoxide from the traditional Chinese medicinal herb Tripterygium wilfordii Hook. f., is a potential treatment for autoimmune diseases as well a possible anti-tumor agent. It inhibits proliferation of coloretal cancer cells in vitro and in vivo. In this study, its ability to block progress of colitis to colon cancer, and its molecular mechanism of action are investigated. A mouse model for colitis-induced colorectal cancer was used to test the effect of triptolide on cancer progression. Treatment of mice with triptolide decreased the incidence of colon cancer formation, and increased survival rate. Moreover, triptolide decreased the incidence of tumors in nude mice inoculated with cultured colon cancer cells dose-dependently. In vitro, triptolide inhibited the proliferation, migration and colony formation of colon cancer cells. Secretion of IL6 and levels of JAK1, IL6R and phosphorylated STAT3 were all reduced by triptolide treatment. Triptolide prohibited Rac1 activity and blocked cyclin D1 and CDK4 expression, leading to G1 arrest. Triptolide interrupted the IL6R-JAK/STAT pathway that is crucial for cell proliferation, survival, and inflammation. This suggests that triptolide might be a candidate for prevention of colitis induced colon cancer because it reduces inflammation and prevents tumor formation and development.

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“…Due to its crucial role in cell apoptosis, the mitochondria have emerged as a novel pharmacological target for anticancer chemotherapy (5,6). A number of anticancer chemotherapeutic drugs that act on mitochondrial targets are under investigation.…”

Section: Introductionmentioning

confidence: 99%

Subcellular location of antitumor tripeptide-tyroserleutide in human hepatocellular carcinoma cells

Zhang

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. Tyroserleutide (YSL) is a tripeptide compound that exhibits potent antitumor activity in human tumor xenografts and tumor cell lines. However, the target of YSL on which it exerts its antitumor activity has yet to be identified. Therefore, our study aimed to investigate the subcellular location of YSL in BEL-7402 human hepatocellular carcinoma cells. Using methods of fluorescent tracing and confocal colocalization, we provide evidence that when BEL-7402 cells are treated with YSL, YSL is distributed in the cytoplasm and colocalized with the mitochondria of cancer cells. Furthermore, we observed the effect of YSL on the isolated mitochondria. Using fluorescence spectrophotometry to monitor the Δψ collapse of mitochondria isolated from BEL-7402 cells by reversion of the quenching of tetramethylrhodamine methyl ester (TMRM), we found that the isolated mitochondria reversed the quenching of the fluorescence in the solution containing TMRM and YSL. This indicates that YSL decreases the Δψ of the isolated mitochondria. Another photometry method was used to observe the effect on mitochondrial swelling when YSL acted directly on the isolated mitochondria. We reveal that YSL directly causes mitochondrial swelling in 60 min. In conclusion, this study encloses a preliminary facet of the pharmacological target of YSL, and we speculate that YSL may act directly on the mitochondria to exert its antitumor activity.

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Involvement of Mitochondrial Pathway in Triptolide-Induced Cytotoxicity in Human Normal Liver L-02 Cells

Cited by 95 publications

References 35 publications

Triptolide-induced cell cycle arrest and apoptosis in human renal cell carcinoma cells

Triptolide-induced cell cycle arrest and apoptosis in human renal cell carcinoma cells

Triptolide downregulates Rac1 and the JAK/STAT3 pathway and inhibits colitis-related colon cancer progression

Subcellular location of antitumor tripeptide-tyroserleutide in human hepatocellular carcinoma cells

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