Abstract
Triptolide and celastrol are two main active compounds isolated from Thunder God Vine with the potent anticancer activity. However, the anticancer effect of triptolide in combination with celastrol is still unknown. In the present study, we demonstrated that the combination of triptolide with celastrol synergistically induced cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the increased intracellular ROS accumulation in cancer cells. Pretreatment with ROS scavenger N-acetyl-L-cysteine dramatically blocked the apoptosis induced by co-treatment with triptolide and celastrol. Treatment with celastrol alone led to the decreased expressions of HSP90 client proteins including survivin, AKT, EGFR, which was enhanced by the addition of triptolide. Additionally, the celastrol-induced expression of HSP70 and HSP27 was abrogated by triptolide. In the nude mice with xenograft tumors, the lower-dose combination of triptolide with celastrol significantly inhibited the growth of tumors without obvious toxicity. Overall, triptolide in combination with celastrol showed outstanding synergistic anticancer effect in vitro and in vivo, suggesting that this beneficial combination may offer a promising treatment option for cancer patients.
Keywords:
cancer; celastrol; combination therapy; triptolide.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / isolation & purification
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Antineoplastic Agents / pharmacology*
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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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Apoptosis / drug effects
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Diterpenes / isolation & purification
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Diterpenes / pharmacology*
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Dose-Response Relationship, Drug
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Drug Synergism
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Epoxy Compounds / isolation & purification
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Epoxy Compounds / pharmacology
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G2 Phase Cell Cycle Checkpoints / drug effects
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HSP27 Heat-Shock Proteins / genetics
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HSP27 Heat-Shock Proteins / metabolism
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HSP70 Heat-Shock Proteins / genetics
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HSP70 Heat-Shock Proteins / metabolism
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HSP90 Heat-Shock Proteins / metabolism
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Heat-Shock Proteins
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Humans
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Inhibitory Concentration 50
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Mice, Inbred BALB C
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Mice, Nude
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Molecular Chaperones
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Neoplasms / drug therapy*
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Neoplasms / genetics
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Neoplasms / metabolism
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Neoplasms / pathology
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Pentacyclic Triterpenes
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Phenanthrenes / isolation & purification
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Phenanthrenes / pharmacology*
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Phytotherapy
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Plant Extracts / isolation & purification
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Plant Extracts / pharmacology*
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Plants, Medicinal
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Reactive Oxygen Species / metabolism
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Time Factors
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Transfection
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Tripterygium / chemistry*
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Triterpenes / isolation & purification
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Triterpenes / pharmacology*
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Tumor Burden / drug effects
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Xenograft Model Antitumor Assays
Substances
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Antineoplastic Agents
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Diterpenes
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Epoxy Compounds
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HSP27 Heat-Shock Proteins
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HSP70 Heat-Shock Proteins
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HSP90 Heat-Shock Proteins
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HSPB1 protein, human
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Heat-Shock Proteins
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Molecular Chaperones
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Pentacyclic Triterpenes
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Phenanthrenes
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Plant Extracts
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Reactive Oxygen Species
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Triterpenes
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triptolide
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celastrol