Synergistic anticancer activity of triptolide combined with cisplatin enhances apoptosis in gastric cancer in vitro and in vivo

Li, Chia-Jung; Chu, Ching-Yu; Huang, Lin-Huang; Wang, Ming-Hseng; Sheu, Lai-Fa; Yeh, Jih‐I; Hsu, Hsue-Yin

doi:10.1016/j.canlet.2012.01.006

Cited by 92 publications

(57 citation statements)

References 26 publications

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“…These results were consistent with other agents previously reported, including docetaxel (30), γ-tocotrienol (31), magnolol (32), milk fermented by Propionibacterium freudenreichii (33), triptolide and cisplatin (34).…”

Section: A Bsupporting

confidence: 93%

Crocetin induces apoptosis of BGC-823 human gastric cancer cells

Wang

et al. 2013

Molecular Medicine Reports

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Abstract. Gastric cancer (GC) is one of the most common types of gastrointestinal tumors worldwide, and the side effects of chemotherapeutic drugs and the resistance to chemotherapy remain problematic in its clinical treatment. Therefore, safe and effective novel agents are urgently required. The purpose of the present study was to investigate the crocetin-sensitive treatment of GC and its possible mechanisms. BGC-823 human GC cells were treated with crocetin. The effects of crocetin on the viability of the cells were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Hoechst 33258 dyeing and Rh123 staining were used to detect cell apoptosis. The BGC-823 cells were subjected to western blotting analysis for detection of cytochrome c and cleaved caspase-3 protein expression. Crocetin inhibited the proliferation of the GC cell line in a dose-and time-dependent manner. Apoptotic BGC-823 cells induced by crocetin were stained by Hoechst 33258 and observed under a light microscope for cell membrane staining of dense nuclei, nuclear pyknosis, fragmentation, chromatin condensation and highlighted nuclear membrane staining. This revealed a decline in the mitochondrial membrane potential of the BGC-823 cells. Crocetin also induced caspase-3 activation and cytochrome c translocation into the cytosol from the mitochondria. The results of this study indicate that crocetin induces the apoptosis of BGC-823 cells, and may be used as an effective agent in the treatment of GC.

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Section: A Bsupporting

confidence: 93%

Crocetin induces apoptosis of BGC-823 human gastric cancer cells

Wang

et al. 2013

Molecular Medicine Reports

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“…Previous research has demonstrated that the drug additionally possesses potent antitumor activity, and is able to synergistically enhance the antitumor activities of conventional chemotherapeutic drugs (19,20). In the present study, the cooperative antitumor activities of triptolide and gemcitabine were investigated in vitro in pancreatic cancer cells.…”

Section: Discussionmentioning

confidence: 91%

“…In addition to immunosuppressive activity, triptolide has been demonstrated to possess potent antitumor activity and induce apoptosis in a variety of tumor types in vivo and in vitro (16)(17)(18). Furthermore, triptolide has been reported to synergistically increase the antitumor activities of conventional chemotherapies (19,20). Synergistic antitumor interactions between triptolide and other chemotherapeutic drugs, including cisplatin, artesunate and hydroxycamptothecin, have been previously observed in pancreatic cancer cells (21)(22)(23).…”

Section: Introductionmentioning

confidence: 92%

Synergistic antitumor activity of gemcitabine combined with triptolide in pancreatic cancer cells

Qiao

et al. 2016

Oncology Letters

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Abstract. Pancreatic cancer is a fatal human malignancy associated with an exceptionally poor prognosis. Novel therapeutic strategies are urgently required to treat this disease. In addition to immunosuppressive activity, triptolide possesses strong antitumor activity and synergistically enhances the antitumor activities of conventional chemotherapeutic drugs in preclinical models of pancreatic cancer. The present study investigated the antitumor effects of triptolide in pancreatic cancer cells, either in combination with gemcitabine, or alone. The pancreatic cancer BxPC-3 and PANC-1 cell lines were treated with triptolide, which resulted in time-and dose-dependent growth arrest. When incorporated into a sequential schedule, triptolide synergistically increased gemcitabine-induced cell growth inhibition and apoptosis, in addition to the cooperative regulation of B-cell lymphoma 2 family proteins and loss of mitochondrial membrane potential. Furthermore, triptolide enhanced gemcitabine-induced S phase arrest and DNA double-strand breaks, possibly through checkpoint kinase 1 suppression. The results of the present study suggest that triptolide has therapeutic potential for the treatment of pancreatic cancer, particularly when administered in combination with gemcitabine. IntroductionPancreatic cancer is an aggressive and highly fatal malignancy affecting a large number of individuals worldwide, and has a relative 5-year survival rate of <5% (1,2). It is the fourth leading cause of cancer-associated mortality in the United States, with ~46,420 new cases and 39,590 fatalities occurring as a result of the disease during 2014 (3). Surgical resection is currently the only treatment available that may cure pancreatic cancer (4); however, the majority of patients are diagnosed late in the natural course of the disease, with ~80% presenting with metastasis (5,6).The drug 2',2'-difluorodeoxycytidine, also known as gemcitabine, is the first-line chemotherapeutic agent for pancreatic cancer treatment that is approved by the Food and Drug Administration (7,8). It exerts antitumor activity depending on several inhibitory actions of DNA synthesis, functioning to impair DNA repair and induce apoptosis (9). Gemcitabine has been demonstrated to effectively inhibit pancreatic cancer cells that are insensitive to other drugs, including fluorouracil, doxorubicin and cisplatin (10). Although gemcitabine exhibits effective inhibition on pancreatic cancer cell growth in vitro, its clinical efficacy remains low (11). Thus, novel therapies are urgently required for the treatment of this extremely aggressive malignancy.Triptolide is a diterpenoid triepoxide derived from the herb Tripterygium wilfordii, which has been utilized as a natural agent in China for centuries (12). Triptolide has been successfully applied as an immunosuppressant for clinical treatment of inflammation, autoimmune diseases and organ transplantations (13-15). In addition to immunosuppressive activity, triptolide has been demonstrated to possess potent antitumor activi...

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“…Apart from its own biological activities triptolide modulates the activity of different popular commercial antitumor drugs that indicates its chemo-sensitizing property. [54][55][56][57][58][59] A major problem associated with the anti-tumor activity of triptolide is its lower solubility in water and greater cytotoxicity that limits its use of clinical study. Therefore, to increase its bioavailability, Xu and colleagues 88 developed polymeric micelles that reduce the triptolide toxicity and increase Poly (D, L-lactic acid) nanoparticles are another very promising carripaire for triptolide that can reduce renal toxicity in rats.…”

Section: Resultsmentioning

confidence: 99%

“…Apoptosis was accompanied by loss of mitochondrial membrane potential, cytochrome-C release and Caspase activation. 57 In another study, Cai and others showed that Triptolide in combination with curcumin synergistically inhibited the growth of ovarian cancer cells and apoptosis induced by loss of mitochondrial membrane potential, ROS generation and down regulation of Hsp27 and Hsp70 genes. 58 Not only chemotherapeutic drug, Triptolide could enhance the anti-tumor effect of ionizing radiation.…”

Section: Combination Therapymentioning

confidence: 98%

Triptolide Mediated Amelioration of Breast Cancer via Modulation of Molecular Pathways

Sarkar

Paul

2017

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Triptolide is the main bioactive molecule isolated from a root extract of Tripterigium wilfordii Hook F. of Celastraceae family. Chemically, it is a diterpenoid triepoxide molecule and its chemical formula is C 20 H 24 O 6 . Its five-membered unsaturated lactone ring (D-ring) is crucial for anti-tumor potential and carbonyl group at C-18 position is essential to exert important influence on the interaction between triptolide and the targeted protein(s). It is bio-synthesized from deoxy-D-xylullose-5-phosphate (DOXP) pathway in the cell. Triptolide can induce apoptosis in a number of breast cancer cells by up-regulating different pro-apoptotic and down-regulating different anti-apoptotic molecules. In vitro experiments indicate that it can down regulate several cell cycle related genes and induces S-phase cell cycle arrest. Triptolide treatment can also modulate the expression of different cell signaling molecules, e.g. ERK, NF-κB, FAK, VEGF, β-catenin, AKT etc. In vivo experiments indicate that triptolide can effectively reduce breast tumor growth in the mouse model. Apart from the single drug treatment, triptolide can effectively be applied in combination therapy. Application of Triptolide with other chemotherapeutic drugs, very efficiently check the proliferation of tumor cells which reduces the effective concentration of the commercially available drugs thus reducing their toxic sideeffects. Although triptolide is very effective against a number of diseases, its higher degree of multi-organ toxicity limits its use of further clinical trial. Therefore, to reduce the toxic effects, a number of strategies have been developed which increase its water solubility and at the same time decrease the toxic effect. In this review article, we have addressed how triptolide participates in the antitumor processes in breast can cer cells.

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Synergistic anticancer activity of triptolide combined with cisplatin enhances apoptosis in gastric cancer in vitro and in vivo

Cited by 92 publications

References 26 publications

Crocetin induces apoptosis of BGC-823 human gastric cancer cells

Crocetin induces apoptosis of BGC-823 human gastric cancer cells

Synergistic antitumor activity of gemcitabine combined with triptolide in pancreatic cancer cells

Triptolide Mediated Amelioration of Breast Cancer via Modulation of Molecular Pathways

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