Evaluation of the mutagenic, cytotoxic, and antitumor potential of triptolide, a highly oxygenated diterpene isolated from Tripterygium wilfordii

Shamon, Lisa A.; Pezzuto, John M.; Graves, J. M.; Mehta, Rajeshwari R.; Wangcharoentrakul, Sirichai; Sangsuwan, Ranee; Chaichana, Suttiporn; Tuchinda, Patoomratana; Cleason, Per; Reutrakul, Vichai

doi:10.1016/s0304-3835(96)04554-5

Cited by 150 publications

(114 citation statements)

References 14 publications

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“…In this model, triptolide was administered at 0.15 mg/kg four times per week. This dose was lower than those reported previously (Shamon et al, 1997;Fidler et al, 2003;Yang et al, 2003) and we could use safely without any remarkable adverse effects, but this low concentration could still enhance cancer-specific CDDP-induced cytotoxicity. When we consider clinical application of triptolide at a low concentration with chemotherapeutic agents to overcome its disadvantage, which is the narrow therapeutic window, a combination with CDDP, which is one of the most frequently used agents for urothelial cancer, is a very attractive choice.…”

Section: Discussionmentioning

confidence: 50%

“…Its high antiproliferative efficiency is attractive for clinical applications, and phase É clinical trials using PG490-88, a water-soluble prodrug of triptolide, have been already attempted in Europe. However, as Shamon et al (1997) reported using a xenograft model, its narrow therapeutic window would be a problem when used as a single agent, and therefore the benefit of the combination use of triptolide at low concentrations with conventional chemotherapeutic agents such as doxorubicin and CPT-11 has been intended (Fidler et al, 2003;Carter et al, 2006). In this study, we demonstrated the usefulness of triptolide at subtoxic concentrations to enhance CDDP-induced cytotoxicity in urothelial cancer cells with wild-type p53, without synergic toxicity to normal urothelium.…”

Section: Discussionmentioning

confidence: 99%

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Cancer-specific enhancement of cisplatin-induced cytotoxicity with triptolide through an interaction of inactivated glycogen synthase kinase-3β with p53

et al. 2008

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To improve conventional chemotherapeutic efficacy, a combination use of traditional medicines is effective but detailed mechanisms have been rarely elucidated. In the this study, we attempted to clarify how triptolide (PG490), an oxygenated diterpene derived from a Chinese herb, enhances the cisplatin (CDDP)-induced cytotoxicity in urothelial cancer cells. Our results showed that a combined CDDP/triptolide therapy induced apoptosis in urothelial cancer cell lines with wild-type p53, but not in those with mutant-type p53 or normal human urothelium. As the mechanism, triptolide suppressed CDDP-induced p53 transcriptional activity, leading to p21 attenuation, which promoted apoptosis via the activation of c-Jun N-terminal kinase (JNK) and Bax. We further demonstrated that the functional regulation of p53 by triptolide was mediated by an intranuclear association of p53 with glycogen synthase kinase-3b (GSK3b), which was inactivated by protein kinase C (PKC). This modulation of the PKC-GSK3b axis by triptolide was observed in a cancer-specific manner. A mouse xenograft model also showed that a combined CDDP/triptolide therapy completely suppressed tumor growth without any side effects. We expect that cancer-specific enhancement of CDDP-induced cytotoxicity with triptolide may effectively overcome the resistance to a CDDP-based conventional chemotherapy as a treatment for urothelial cancer.

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Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Cancer-specific enhancement of cisplatin-induced cytotoxicity with triptolide through an interaction of inactivated glycogen synthase kinase-3β with p53

et al. 2008

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“…In addition to western therapies for cancer prevention, there are also studies on anti-tumor effects of herbal medicines such as D. bulbifera, Tripterygium wilfordii, and Andrographis paniculata (Shamon et al, 1997;Gao et al, 2002;Kumar et al, 2004). Compatibility is a main principle of Chinese medicinal herbs, and some reports have demonstrated that compatibility may lead to eliminating toxicity or reinforcing bioactivities (Kim et al, 2007;Gao et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Ferulic acid prevents liver injury and increases the anti-tumor effect of diosbulbin B in vivo

Wang

Sheng

et al. 2014

J. Zhejiang Univ. Sci. B

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Abstract:The present study is designed to investigate the protection by ferulic acid against the hepatotoxicity induced by diosbulbin B and its possible mechanism, and further observe whether ferulic acid augments diosbulbin Binduced anti-tumor activity. The results show that ferulic acid decreases diosbulbin B-increased serum alanine transaminase/aspartate transaminase (ALT/AST) levels. Ferulic acid also decreases lipid peroxide (LPO) levels which are elevated in diosbulbin B-treated mice. Histological evaluation of the liver demonstrates hydropic degeneration in diosbulbin B-treated mice, while ferulic acid reverses this injury. Moreover, the activities of copper-and zinc-containing superoxide dismutase (CuZn-SOD) and catalase (CAT) are decreased in the livers of diosbulbin B-treated mice, while ferulic acid reverses these decreases. Further results demonstrate that the mRNA expressions of CuZn-SOD and CAT in diosbulbin B-treated mouse liver are significantly decreased, while ferulic acid prevents this decrease. In addition, ferulic acid also augments diosbulbin B-induced tumor growth inhibition compared with diosbulbin B alone. Taken together, the present study shows that ferulic acid prevents diosbulbin B-induced liver injury via ameliorating diosbulbin B-induced liver oxidative stress injury and augments diosbulbin B-induced anti-tumor activity.

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“…It has potent antiproliferative and proapoptotic activities with many types of cancer cells and transformed cell line in vitro and in vivo [18][19][20]. Recent studies show that triptolide executes anti-neoplastic effect [21][22][23] and a functional p53 is required for the proapoptotic effect [24].…”

Section: Introductionmentioning

confidence: 99%

Differential regulation of survivin by p53 contributes to cell cycle dependent apoptosis

et al. 2005

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Recent studies indicate that cell-cycle checkpoints are tightly correlated with the regulation of apoptosis, in which p53 plays an important role. Our present works show that the expression of E6/E7 oncogenes of human papillomavirus in HeLa cells is inhibited in the presence of anti-tumor reagent tripchlorolide (TC), which results in the up-regulation of p53 in HeLa cells. Interestingly, under the same TC-treatment, the cells at the early S-phase are more susceptible to apoptosis than those at the middle S-phase although p53 protein is stabilized to the same level in both situations. Significant difference is exhibited between the two specified expression profiles. Further analysis demonstrates that anti-apoptotic gene survivin is up-regulated by p53 in the TC-treated middle-S cells, whereas it is down-regulated by p53 in the TC-treated early-S cells. Taken together, the present study indicates that the differential p53-regulated expression of survivin at different stages of the cell cycle results in different cellular outputs under the same apoptosis-inducer.

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Evaluation of the mutagenic, cytotoxic, and antitumor potential of triptolide, a highly oxygenated diterpene isolated from Tripterygium wilfordii

Cited by 150 publications

References 14 publications

Cancer-specific enhancement of cisplatin-induced cytotoxicity with triptolide through an interaction of inactivated glycogen synthase kinase-3β with p53

Cancer-specific enhancement of cisplatin-induced cytotoxicity with triptolide through an interaction of inactivated glycogen synthase kinase-3β with p53

Ferulic acid prevents liver injury and increases the anti-tumor effect of diosbulbin B in vivo

Differential regulation of survivin by p53 contributes to cell cycle dependent apoptosis

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