Triptolide: structural modifications, structure–activity relationships, bioactivities, clinical development and mechanisms

Zhou, Zhaoli; Yang, Yaxi; Ding, Jian; Li, Yuanchao; Miao, Ze‐Hong

doi:10.1039/c2np00088a

Cited by 266 publications

(217 citation statements)

References 126 publications

(181 reference statements)

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“…28 In addition, TPL was proved efficient in reducing tumor growth and prolonging the living time. [29][30][31] TPL can also enhance the activities of chemotherapeutic agents in colon carcinoma cells, myeloma cell lines, and human oral cavity squamous cell carcinoma cells. [32][33][34] As reported, the combination of TPL with other anticancer drugs resulted in synergistic effects and promoted apoptosis but did not intensify the side effects of chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment

Wu¹,

Lu²,

Zhang³

et al. 2017

IJN

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Codelivery is a promising strategy to overcome the limitations of single chemotherapeutic agents in cancer treatment. Despite progress, codelivery of two or more different functional drugs to increase anticancer efficiency still remains a challenge. Here, reduction-sensitive lipid–polymer hybrid nanoparticles (LPNPs) drug delivery system composed of monomethoxy-poly(ethylene glycol)- S - S -hexadecyl (mPEG- S - S -C 16 ), soybean lecithin, and poly(D,L-lactide-co-glycolide) (PLGA) was used for codelivery of doxorubicin (DOX) and a Chinese herb extract triptolide (TPL). Hydrophobic DOX and TPL could be successfully loaded in LPNPs by self-assembly. More importantly, drug release and cellular uptake experiments demonstrated that the two drugs were reduction sensitive, released simultaneously from LPNPs, and taken up effectively by the tumor cells. DOX/TPL-coloaded LPNPs (DOX/TPL-LPNPs) exhibited a high level of synergistic activation with low combination index (CI) in vitro and in vivo. Moreover, the highest synergistic therapeutic effect was achieved at the ratio of 1:0.2 DOX/TPL. Further experiments showed that TPL enhanced the uptake of DOX by human oral cavity squamous cell carcinoma cells (KB cells). Overall, DOX/TPL-coencapsulated reduction-sensitive nanoparticles will be a promising strategy for cancer treatment.

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Section: Introductionmentioning

confidence: 99%

Codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment

Wu¹,

Lu²,

Zhang³

et al. 2017

IJN

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“…We also found that of the 17 identified antiangiogenic compounds, 4 compounds, namely, pseudolaric acid B, MFTZ-1, 10-hydroxycamptothecin and triptolide, can indirectly inhibit the VEGF-VEGFR axis by decreasing cellular HIF-1α accumulation and thereby reducing VEGF expression and secretion [15][16][17][18][19][20][21] (Figure 1). We define these compounds to be HIF-1α-VEGF axis inhibitors.…”

Section: Hif-1α-vegf Axis Inhibitorsmentioning

confidence: 97%

“…In contrast to the previous 3 inhibitors, triptolide may enhance the levels of cellular HIF-1α mRNA and protein [20] . However, triptolide also causes the downregulation of VEGF expression and secretion [20] , possibly because it binds to XPB (which is also known as ERCC3) and causes the degradation of RNA polymerase II [21] , disrupting the transcriptional function of HIF-1α.…”

Section: Hif-1α-vegf Axis Inhibitorsmentioning

confidence: 99%

“…In particular, through drug discovery guided by therapeutic experiences from long-established TCM practices, inhibitors of angiogenesis could be obtained that have new chemical structures and unique mechanisms of action; examples of these sorts of inhibitors include pseudolaric acid B, triptolide, 11,11'-dideoxyverticillin and shiraiachrome A ( Table 1). The original medicinal materials producing these compounds have long been used to either treat various angiogenesisrelated diseases, such as rheumatoid arthritis, microbial skin diseases and psoriasis [7,21,23] , or cause the early termination of pregnancies [23] . (2) Marine-derived compounds could be another important source of angiogenesis inhibitors, and certain compounds with specific types of chemical structures, such as saccharides, should be subjected to particular scrutiny; as demonstrated by JG3 [27] and GLP [30] , these compounds may exhibit unique modes of antiangiogenic activity.…”

Section: Ecm Component Inhibitorsmentioning

confidence: 99%

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Newly discovered angiogenesis inhibitors and their mechanisms of action

Feng

Ding

2012

Acta Pharmacol Sin

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In the past decade, the success of angiogenesis inhibitors in clinical contexts has established the antiangiogenic strategy as an important part of cancer therapy. During that time period, we have discovered and reported 17 compounds that exert potent inhibition on angiogenesis. These compounds exhibit tremendous diversity in their sources, structures, targets and mechanisms. These studies have generated new models for further modification and optimization of inhibitory compounds, new information for mechanistic studies and a new drug candidate for clinical development. In particular, through studies on the antiangiogenic mechanism of pseudolaric acid B, we discovered a novel mechanism by which the stability of hypoxia-inducible factor 1α is regulated by the transcription factor c-Jun. We also completed a preclinical study of AL3810, a compound with the potential to circumvent tumor drug resistance to a certain extent. All of these findings will be briefly reviewed in this article.

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“…Triptolide is effective against a number of malignancies, including ovarian cancer, breast cancer, pancreatic cancer and neuroblastoma (6). Triptolide supresses the proliferation of prostate cancer cells by inhibition of expression of SUMO-specific protease 1 (7).…”

Section: Introductionmentioning

confidence: 99%

Triptolide reduces the viability of osteosarcoma cells by reducing MKP-1 and Hsp70 expression

Zhao

Jiang

Wang

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Osteosarcoma is the most common type of malignant bone tumor found in adolescents and young adults. The aim of the present study was to determine whether triptolide, a diterpene epoxide extracted from the Tripterygium plant, was able effectively decrease the viability of osteosarcoma cells. The underlying molecular mechanisms are also investigated. The human osteosarcoma cell lines U-2 OS and MG-63 were used in this study. The U-2 OS and MG-63 cells were treated with 0, 5, 10, 25 or 50 nM triptolide. Cells treated with dimethyl sulfoxide only were used as the no drug treatment control. A commercial MTT kit was used to determine the effects of triptolide on cells. Mitogen-activated protein kinase phosphatase-1 (MKP-1) is frequently overexpressed in tumor tissues, possibly related to the failure of a number of chemotherapeutics. Heat shock protein 70 (Hsp70) is a chaperone molecule that is able to increase drug resistance. The protein expression levels of MKP-1 and Hsp70 were determined using western blot analysis. The results indicate that triptolide effectively reduced the viability of the osteosarcoma cells. Furthermore, triptolide was found to effectively reduce MKP-1 expression and Hsp70 levels. Further analysis showed that triptolide reduced MKP-1 mRNA expression in the U-2 OS and MG-63 cells. Triptolide reduced Hsp70 mRNA expression levels in U-2 OS and MG-63 cells. These results suggest that triptolide effectively decreases the viability of osteosarcoma cells. These effects may be associated with the decreased expression of MKP-1 and Hsp70 levels. These results suggest that triptolide may be used in the treatments of osteosarcoma.

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Triptolide: structural modifications, structure–activity relationships, bioactivities, clinical development and mechanisms

Cited by 266 publications

References 126 publications

Codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment

Codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment

Newly discovered angiogenesis inhibitors and their mechanisms of action

Triptolide reduces the viability of osteosarcoma cells by reducing MKP-1 and Hsp70 expression

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Triptolide: structural modifications, structure–activity relationships, bioactivities, clinical development and mechanisms

Cited by 266 publications

References 126 publications

Codelivery of doxorubicin and triptolide with reduction-sensitive lipid&ndash;polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment

Codelivery of doxorubicin and triptolide with reduction-sensitive lipid&ndash;polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment

Newly discovered angiogenesis inhibitors and their mechanisms of action

Triptolide reduces the viability of osteosarcoma cells by reducing MKP-1 and Hsp70 expression

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Product

Resources

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Codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment

Codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment