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Synergistic anticancer effects of triptolide and celastrol, two main compounds from thunder god vine.
- Source :
-
Oncotarget [Oncotarget] 2015 Oct 20; Vol. 6 (32), pp. 32790-804. - Publication Year :
- 2015
-
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.
- Subjects :
- Animals
Antineoplastic Agents isolation & purification
Apoptosis drug effects
Cell Line, Tumor
Cell Proliferation drug effects
Diterpenes isolation & purification
Dose-Response Relationship, Drug
Drug Synergism
Epoxy Compounds isolation & purification
Epoxy Compounds pharmacology
G2 Phase Cell Cycle Checkpoints drug effects
HSP27 Heat-Shock Proteins genetics
HSP27 Heat-Shock Proteins metabolism
HSP70 Heat-Shock Proteins genetics
HSP70 Heat-Shock Proteins metabolism
HSP90 Heat-Shock Proteins metabolism
Heat-Shock Proteins
Humans
Inhibitory Concentration 50
Mice, Inbred BALB C
Mice, Nude
Molecular Chaperones
Neoplasms genetics
Neoplasms metabolism
Neoplasms pathology
Pentacyclic Triterpenes
Phenanthrenes isolation & purification
Phytotherapy
Plant Extracts isolation & purification
Plants, Medicinal
Reactive Oxygen Species metabolism
Time Factors
Transfection
Triterpenes isolation & purification
Tumor Burden drug effects
Xenograft Model Antitumor Assays
Antineoplastic Agents pharmacology
Antineoplastic Combined Chemotherapy Protocols pharmacology
Diterpenes pharmacology
Neoplasms drug therapy
Phenanthrenes pharmacology
Plant Extracts pharmacology
Tripterygium chemistry
Triterpenes pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 6
- Issue :
- 32
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 26447544
- Full Text :
- https://doi.org/10.18632/oncotarget.5411