Synergistic anticancer effects of triptolide and celastrol, two main compounds from thunder god vine

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.

Metabolomics profiles delineate uridine deficiency contributes to mitochondria-mediated apoptosis induced by celastrol in human acute promyelocytic leukemia cells

“…Indeed, celastrol produced significant pro-apoptotic effect on APL cells at concentrations ≤ 1 μM. As previous reports, at this concentration celastrol had no adverse effect on normal cells [13]. Our animal study also confirmed that celastrol had no systemic toxicity on tumor-bearing mice at the pharmacological dose with significant inhibitory effect on tumor growth.…”

Triptolide and celastrol loaded silk fibroin nanoparticles show synergistic effect against human pancreatic cancer cells

“…Furthermore, the increased β-sheet formation induced by TPL or CL may benefit their encapsulation in the SFNPs leading to slow drug release in later applications. 40 …”

“…The equation to calculate the combination index is CI = (D) 1 /(Dx) 1 + (D) 2 /(Dx) 2 , where (Dx) 1 and (Dx) 2 indicate the individual dose of either free drugs or drug loaded SFNPs required to inhibit a given level of cell growth, and (D) 1 and (D) 2 are the doses of free drugs and drug loaded SFNPs necessary to produce the equal effect in combination, respectively. 38–40 Combination index (CI) value <1, =1 and >1 indicate synergism, additive effect and antagonism, respectively.…”

“…17–20 Combination of low doses of TPL and CL can induce significant pancreatic cancer cell death compared to treatment with either drug alone. 21 Therefore, TPL and CL combination is a viable strategy to enable effective treatment of pancreatic cancer. However, there are still some critical issues that remain to be solved during combination treatment.…”

Triptolide induces DNA breaks, activates caspase-3-dependent apoptosis and sensitizes B-cell lymphoma to poly(ADP-ribose) polymerase 1 and phosphoinositide 3-kinase inhibitors

“…A number of studies have identified that triptolide also exhibits antitumor activity, inhibiting proliferation and migration of cancer cells (8)(9)(10)(11)(12). A previous study has demonstrated that triptolide inhibited ATPase activity of the basal transcription factor transcription factor II H (TFIIH) and RNA polymerase II-mediated transcription in nucleotide excision repair (NER) (13).…”