Triptolide induces mitochondria-mediated apoptosis of Burkitt's lymphoma cell via deacetylation of GSK-3β by increased SIRT3 expression

Kong, Jinliang; Wang, Li; Ren, Lu; Yan, Yichao; Cheng, Yisen; Huang, Zhiying; Shen, Feihai

doi:10.1016/j.taap.2018.01.011

Cited by 19 publications

(16 citation statements)

References 45 publications

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“…Triptolide is shown to exhibit pro-apoptosis effects in various cancers [427][428][429][430][431]. It induces mitochondrial apoptotic pathway to mediate apoptosis in Burkitt's lumphoma Raji, NAMALWA and Daudi cells, and inhibits tumor growth in Daudi xenograft mice [432], and inhibits cell proliferation through microRNA-181a up-regulation in human neuroblastoma SH-SY5Y cells [433]. Moreover, triptolide induces autophagy to induce apoptosis and inhibit angiogenesis in human osteosarcoma MG63 cells, and breast cancer MCF-7 cells [431,434].…”

Section: Triptolidementioning

confidence: 99%

“…Triptolide is a natural substance, which exerts its anticancer effects through multiple targets. Triptolide is shown to induce mitochondrial-mediated apoptosis in various cancer cells, through decreased mitochondrial membrane potential, Bax and cytochrome c accumulation, PARP and caspase-3 activation, decreased ATP levels, and Bcl-2 down-regulation [432,[438][439][440][441]. Moreover, ERK is also shown to be important in mediating triptolide-induced anti-cancer activities.…”

Section: Triptolidementioning

confidence: 99%

“…Triptolide has wide-spectrum activities in pre-clinical studies, but it has strong side effects and water insolubility, so it is not used in clinical studies. However, some of its derivatives and analogs have been used in clinical studies to test the safety and efficacy on anti-cancer effects [432,[455][456][457]. Omtriptolide, a derivative of triptolide, is highly water soluble, and a phase I clinical trial was conducted in Europe with patients who had refractory and relapsed acute leukemia [432].…”

Section: Triptolidementioning

confidence: 99%

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Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

et al. 2019

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Numerous natural products originated from Chinese herbal medicine exhibit anti-cancer activities, including antiproliferative, pro-apoptotic, anti-metastatic, anti-angiogenic effects, as well as regulate autophagy, reverse multidrug resistance, balance immunity, and enhance chemotherapy in vitro and in vivo. To provide new insights into the critical path ahead, we systemically reviewed the most recent advances (reported since 2011) on the key compounds with anti-cancer effects derived from Chinese herbal medicine (curcumin, epigallocatechin gallate, berberine, artemisinin, ginsenoside Rg3, ursolic acid, silibinin, emodin, triptolide, cucurbitacin B, tanshinone I, oridonin, shikonin, gambogic acid, artesunate, wogonin, β-elemene, and cepharanthine) in scientific databases (PubMed, Web of Science, Medline, Scopus, and Clinical Trials). With a broader perspective, we focused on their recently discovered and/or investigated pharmacological effects, novel mechanism of action, relevant clinical studies, and their innovative applications in combined therapy and immunomodulation. In addition, the present review has extended to describe other promising compounds including dihydroartemisinin, ginsenoside Rh2, compound K, cucurbitacins D, E, I, tanshinone IIA and cryptotanshinone in view of their potentials in cancer therapy. Up to now, the evidence about the immunomodulatory effects and clinical trials of natural anti-cancer compounds from Chinese herbal medicine is very limited, and further research is needed to monitor their immunoregulatory effects and explore their mechanisms of action as modulators of immune checkpoints.

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Section: Triptolidementioning

confidence: 99%

Section: Triptolidementioning

confidence: 99%

Section: Triptolidementioning

confidence: 99%

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Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

et al. 2019

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“…In addition to the selectivity of IKK‐ α and IKK‐ β kinases, these compounds also have better overall kinase selectivity. Among them, compound b showed excellent selectivity to GSK‐3 β , CDK2, ALK5, EGFR, ErbB2, PLK1, VEGFR2, etc . Interestingly, the kinase docking result of compound c with CDK2 showed that the carbonyl oxygen atoms and amino groups on the amines, as well as the amino groups in the parent structure of the compound c , can form hydrogen bonds with the active sites Cys 99 and Glu 97 of CDK2, which indicated that the amide and amino groups on the phenyl ring were the important groups to inhibit the CDK2 kinase activity .…”

Section: Introductionmentioning

confidence: 99%

“…Among them, compound b showed excellent selectivity to GSK-3β, CDK2, ALK5, EGFR, ErbB2, PLK1, VEGFR2, etc. [31] Interestingly, the kinase docking result of compound c with CDK2 showed that the carbonyl oxygen atoms and amino groups on the amines, as well as the amino groups in the parent structure of the compound c, can form hydrogen bonds with the active sites Cys 99 and Glu 97 of CDK2, which indicated that the amide and amino groups on the phenyl ring were the important groups to inhibit the CDK2 kinase activity. [32] By analyzing the structure of the currently reported well-active GSK-3β small molecule inhibitors, such as 1-azakenpaulllone (IC 50 = 0.018 μM), [33] ARÀ A014418 (IC 50 = 0.104 μM), [34,35] compound 21 (IC 50 = 0.007 μM), [36] compound 11 (IC 50 = 0.126 μM), [37] hymenialdisine (IC 50 = 0.035 μM), [38,39] compound 9i (IC 50 = 0.019 μM) [7] (Figure 3), we found GSK-3β inhibitors mainly structured in an amide or lactam.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and in Vitro Tumor Cytotoxicity Evaluation of 3,5‐Diamino‐N‐substituted Benzamide Derivatives as Novel GSK‐3β Small Molecule Inhibitors

Zhou

Zhang

et al. 2019

Chemistry & Biodiversity

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Glycogen synthase kinase‐3 (GSK‐3) plays an important regulatory role in various signaling pathways; such as PI3 K/AKT, which is closely related to the occurrence and development of tumors. At present, the most reported active GSK‐3 inhibitors have the same structure: lactam ring or amide structure. To find out the GSK‐3β small molecule inhibitor with novel, safe, efficient and more uncomplicated synthesis method, we analyzed in‐depth reported crystal‐binding patterns of GSK‐3β small molecule inhibitor with GSK‐3β protein, and designed and synthesized 17 non‐reported 3,5‐diamino‐N‐substituted benzamide compounds. Their structures were confirmed by 1H‐NMR, 13C‐NMR, and HR‐MS. The preliminary screening of tumor cytotoxicity of compounds in vitro was detected by MTT, and their structure–activity relationships were illustrated. The results have shown that 3,5‐diamino‐N‐[3‐(trifluoromethyl)phenyl]benzamide (4d) exhibited significant tumor cytotoxicity against human colon cancer cells (HCT‐116) with IC50 of 8.3 μm and showed commendable selectivity to GSK‐3β. In addition, Compound 4d induced apoptosis to some extent and possessed modest PK properties.

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Low‐dose triptolide enhances antitumor effect of JQ1 on acute myeloid leukemia through inhibiting RNA polymerase II in vitro and in vivo

Shi

Zhao

et al. 2020

Molecular Carcinogenesis

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The bromodomain and extra‐terminal (BET) domain inhibitor JQ1 exerts potent anticancer activity in various cancer cells. However, the resistance to BET inhibitors in leukemia stem cells limits its implication in acute myeloid leukemia (AML). High concentration of triptolide (TPL) presents anticancer activities but with adverse effects. Here, we investigated whether the combination of low‐dose TPL with JQ1 could help to circumvent the dilemma of drug resistance and side effect in treating AML. AML cell lines, primary cells from 10 AML patients with different status, as well as AML mice model were subjected to different treatments and apoptotic related protein expression were evaluated. Data showed that low‐dose TPL combined with JQ1 effectively killed AML cell lines and primary cells from AML patients without exerting significantly greater lethal activity against normal cells. Mechanism study revealed that low‐dose TPL combined with JQ1 triggered reactive oxygen species production and induced mitochondrial‐mediated apoptosis in AML cells, in which the inhibition of RNA polymerase II to downregulate c‐Myc was mainly responsible for the enhanced activity of TPL in combination with JQ1. In vivo study presented that cotreatment with low‐dose TPL and JQ1 significantly reduced tumor burden of the NOD/SCID mice engrafted with MOLM‐13 cells. In conclusion, low‐dose TPL enhanced the antitumor effect of JQ1 on AML without increasing the side effects, supporting a potential option for AML treatment.

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Triptolide induces mitochondria-mediated apoptosis of Burkitt's lymphoma cell via deacetylation of GSK-3β by increased SIRT3 expression

Cited by 19 publications

References 45 publications

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

Design, Synthesis and in Vitro Tumor Cytotoxicity Evaluation of 3,5‐Diamino‐N‐substituted Benzamide Derivatives as Novel GSK‐3β Small Molecule Inhibitors

Low‐dose triptolide enhances antitumor effect of JQ1 on acute myeloid leukemia through inhibiting RNA polymerase II in vitro and in vivo

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