Triptolide inactivates Akt and induces caspase-dependent death in cervical cancer cells via the mitochondrial pathway

Abstract

Abstract. Triptolide, the main active component of the traditional Chinese herbal medicine Tripterygium wilfordii Hook F, has been shown to have potent immunosuppressive and anti-inflammatory properties. Here, we investigated the pro-apoptotic effect of triptolide in human cervical cancer cells and its underlying mechanisms. Exposure of cervical cancer cells to triptolide induced apoptosis, which was accompanied by loss of mitochondrial membrane potential, caspase processing (caspase-8, -9 and -3), and cleavage of the caspase substrate, poly(ADP-ribose) polymerase. The cytotoxic effects of triptolide were significantly inhibited by the caspase inhibitor, z-VAD-fmk. Triptolide-induced apoptosis was associated with a marked reduction in Akt phosphorylation and was exacerbated by LY294002 (phosphatidylinositol-3'-kinase inhibitor). Conversely, it was attenuated by Akt overexpression. Triptolide-induced apoptosis was also associated with downregulation of Mcl-1 and was significantly inhibited by Mcl-1 overexpression. These findings show that triptolide induces caspase-dependent, mitochondria-mediated apoptosis in cervical cancer cells, in part, by negatively regulating Akt and Mcl-1.

Triptolide induces apoptosis of PMA-treated THP-1 cells through activation of caspases, inhibition of NF-κB and activation of MAPKs

“…Triptolide inhibits cell growth in variety of tumor cells (15,16). In this study, human monocytic leukemia THP-1 cells that had been PMA-differentiated showed inhibition of cell proliferation after triptolide treatment, in a dose-and time-dependent manner.…”

“…Triptolide has also been reported to induce significant apoptosis and minor accumulation in the S phase in THP-1 cells (17). However, treatment with triptolide was shown to reduce the viability of HeLa and Caski cells in a concentration-dependent manner and to increase accumulation of sub-G1 phase cells and apoptotic bodies (16).…”

“…Caspase-3 and -9 activity play important roles in apoptosis through a mitochondria-dependent pathway. It has been shown that the induction of apoptosis in cervical cancer cells by triptolide is associated with activation of caspases (16). Moreover, it was reported that triptolide may induce apoptosis through a mitochondria-mediated apoptotic pathway in a caspase-dependent way in human melanoma A375 cells (22).…”

Combined Effects of Curcumin and Triptolide on an Ovarian Cancer Cell Line

“…Recently, curcumin (Yu et al, 2011;Li et al, 2013;Zhou et al, 2013;Yin et al, 2013) and triptolide (Kim et al, 2010;Liu et al, 2012;Wen et al, 2012) are able to potently inhibit the growth of human cancer cells in vitro and prevents tumor growth in vivo via inhibiting cell proliferation and inducing apoptosis. However, both of curcumin and triptolide possess side effects in high concentration (Banjerdpongchai et al, 2005;Clawson et al, 2010;Antonoff et al, 2010;Li et al, 2010;Borja-Cacho et al, 2010;Shakibaei et al, 2013;Du et al, 2013;Jiang et al, 2013).…”

Tripterygium Wilfordii Extract (Triptolide) and Amygdalin Promotes Cell death in Cancer Cells: True or a Myth

“…[8][9][10][11][12][13][14][15] Moreover, Triptolide proapoptotic and antiproliferative activity has also been associated with a numerous cancer cell lines in vitro and in vivo such as: HL-60, T cell lymphoma (Jurkat), U937, OCI-AML3 Kasumi-1 and SKNO-1 cells, human hepatocellular carcinoma SMMC-7721 cells, and cell lines of multiple myeloma, breast, gastric, prostate, lung, oral, colon, pancreatic and cervical cancers, cholangiocarcinoma, and neuroblastoma. [8][9][10][11][12][13][14][15] In vivo trials confirmed the therapeutic activity of Triptolide in a number of model systems including hamster models, human melanoma xenografts, gastric carcinoma, breast cancer, pancreatic cancer, bladder cancer and neuroblastoma in nude mice studies. [16,18] Moreover, Triptolide has been shown to fortify other agents helping as combination with other drugs to improve their cancer treatment abilities.…”