Research progress on the relationship between celastrol and tumor metabolism

Li Ye; Song Mengmeng; Chang Wenjun; Miao Mingyong; Pan Yamin

doi:10.16689/j.cnki.cn11-9349/r.2020.01.004

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Electronic Journal of Metabolism and Nutrition of Cancer ›› 2020, Vol. 7 ›› Issue (1) : 18-21. DOI: 10.16689/j.cnki.cn11-9349/r.2020.01.004

Research progress on the relationship between celastrol and tumor metabolism

1 Li Ye,2 Song Mengmeng,3 Chang Wenjun,4 Miao Mingyong,1 Pan Yamin

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Abstract

Celastrol is an active ingredient of Chinese herbal medicine with extensive therapeutic properties and high medicinal value. It is commonly used in the treatment of autoimmune diseases, metabolic diseases and cancer. Celastrol can inhibit the occurrence and development of tumor through a variety of ways, especially closely related to tumor metabolism, and has an important impact on the metabolism of sugar metabolism, lipid metabolism, amino acid metabolism and tumor microenvironment of tumor cells. Celastrol causes mitochondrial dysfunction to alter the glucose metabolism pathway, resulting in insufficient energy supply to tumor cells； affects lipid metabolism in tumor hosts by inducing liver Sirt1 expression； inhibits the progress of colorectal cancer by inhibiting indoleamine 2,3 dioxygenase (IDO) expression and tryptophan catabolism, controls pancreatic cancer by combining with IDO inhibitor D-1MT. In the tumor microenvironment, celastrol can treat melanoma by inhibiting NLRP3 inflammatory bodies and remodeling immunosuppression. According to the latest research, the high metabolism of intestinal flora can improve the efficacy of celastrol in the body, affecting the development of tumors. This review describes the main effects and mechanisms of celastrol on tumors from a metabolic perspective, providing a scientific basis for its in-depth study of pharmacological effects.

Key words

Celastrol / Tumor metabolism / Tumor microenvironment / Intestinal flora

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Li Ye,Song Mengmeng,Chang Wenjun,Miao Mingyong,Pan Yamin. Research progress on the relationship between celastrol and tumor metabolism[J]. Electronic Journal of Metabolism and Nutrition of Cancer. 2020, 7(1): 18-21 https://doi.org/10.16689/j.cnki.cn11-9349/r.2020.01.004

References

1.Kannaiyan R, Shanmugam MK, Sethi G. Molecular targets of celastrol derived from Thunder of God Vine： potential role in the treatment of inflammatory disorders and cancer. Cancer Lett. 2011；303(1)：9-20.
2.Kuchta K, Xiang Y, Huang S, et al. Celastrol, an active constituent of the TCM plant Tripterygium wilfordii Hook.f., inhibits prostate cancer bone metastasis. Prostate Cancer Prostatic Dis. 2017；20(2)：156-164.
3.Liu X, Zhao P, Wang X, et al. Celastrol mediates autophagy and apoptosis via the ROS/JNK and Akt/mTOR signaling pathways in glioma cells. J Exp Clin Cancer Res. 2019；38(1)：184-186.
4.Yao SS, Han L, Tian ZB, et al. Celastrol inhibits growth and metastasis of human gastric cancer cell MKN45 by down-regulating microRNA-21. Phytother Res. 2019；33(6)：1706-1716.
5.Gao Y, Zhou S, Pang L, et al. Celastrol suppresses nitric oxide synthases and the angiogenesis pathway in colorectal cancer. Free Radic Res. 2019；53(3)：324-334.
6.Lin L, Sun Y, Wang D, et al. Celastrol ameliorates ulcerative colitis-related colorectal cancer in mice via suppressing inflammatory responses and epithelial-mesenchymal transition. Front Pharmacol. 2015；6：320.
7.Hanahan D, Weinberg RA. Hallmarks of cancer： the next generation. Cell. 2011；144(5)：646-674.
8.Koppenol WH, Bounds PL, Dang CV. Otto Warburgs contributions to current concepts of cancer metabolism. Nat Rev Cancer. 2011；11(5)：325-337.
9.Li J, Huang Q, Long X, et al. Mitochondrial elongation-mediated glucose metabolism reprogramming is essential for tumour cell survival during energy stress. Oncogene. 2017；36(34)：4901-4912.
10.Hu Y, Qi Y, Liu H, et al. Effects of celastrol on human cervical cancer cells as revealed by ion-trap gas chromatography-mass spectrometry based metabolic profiling. Biochim Biophys Acta. 2013；1830(3)：2779-2789.
11.Abu Bakar MH, Tan JS. Improvement of mitochondrial function by celastrol in palmitate-treated C2C12 myotubes via activation of PI3K-Akt signaling pathway. Biomed Pharmacother. 2017；93(2)：903-912.
12.Abu Bakar MH, Sarmidi MR, Tan JS, et al. Celastrol attenuates mitochondrial dysfunction and inflammation in palmitate-mediated insulin resistance in C3A hepatocytes. Eur J Pharmacol. 2017；799(1)：73-83.
13.Kim JE, Lee MH, Nam DH, et al. Celastrol, an NF-kappaB inhibitor, improves insulin resistance and attenuates renal injury in db/db mice. PLoS One. 2013；8(4)：e62068.
14.Han LP, Li CJ, Sun B, et al. Protective effects of celastrol on diabetic liver injury via TLR4/MyD88/NF-kappaB signaling pathway in Type 2 diabetic rats. J Diabetes Res. 2016；2016：2641248.
15.Grant CW, Moran-Paul CM, Duclos SK, et al. Testing agents for prevention or reversal of type 1 diabetes in rodents. PLoS One. 2013；8(8)：e72989.
16.Pascual G, Avgustinova A, Mejetta S, et al. Targeting metastasis-initiating cells through the fatty acid receptor CD36. Nature. 2017；541(7635)：41-45.
17.Beloribi-Djefaflia S, Vasseur S, Guillaumond F. Lipid metabolic reprogramming in cancer cells. Oncogenesis. 2016；5：e189.
18.Zhang T, Zhao Q, Xiao XR, et al. Modulation of lipid metabolism by celastrol. J Proteome Res. 2019；18(3)：1133-1144.
19.Zhang Y, Geng C, Liu X, et al. Celastrol ameliorates liver metabolic damage caused by a high-fat diet through Sirt1. Mol Metab. 2017；6(1)：138-147.
20.Liu J, Lee J, Salazar Hernandez MA, et al. Treatment of obesity with celastrol. Cell. 2015；161(5)：999-1011.
21.Feng X, Guan D, Auen T, et al. IL1R1 is required for celastrols leptin-sensitization and antiobesity effects. Nat Med. 2019；25(4)：575-582.
22.Tsun ZY, Possemato R. Amino acid management in cancer. Semin Cell Dev Biol. 2015；43：22-32.
23.Bhutia YD, Babu E, Ramachandran S, et al. Amino Acid transporters in cancer and their relevance to "glutamine addiction"： novel targets for the design of a new class of anticancer drugs. Cancer Res. 2015；75(9)：1782-1788.
24.Uyttenhove C, Pilotte L, Theate I, et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med. 2003；9(10)：1269-1274.
25.Okamoto A, Nikaido T, Ochiai K, et al. Indoleamine 2,3-dioxygenase serves as a marker of poor prognosis in gene expression profiles of serous ovarian cancer cells. Clin Cancer Res. 2005；11(16)：6030-6039.
26.Brandacher G, Perathoner A, Ladurner R, et al. Prognostic value of indoleamine 2,3-dioxygenase expression in colorectal cancer： effect on tumor-infiltrating T cells. Clin Cancer Res. 2006；12(4)：1144-1151.
27.Ninomiya S, Hara T, Tsurumi H, et al. Indoleamine 2,3-dioxygenase in tumor tissue indicates prognosis in patients with diffuse large B-cell lymphoma treated with R-CHOP. Ann Hematol. 2011；90(4)：409-416.28.Sharma P, Allison JP. Immune checkpoint targeting in cancer therapy： toward combination strategies with curative potential. Cell. 2015；161(2)：205-214.
28.Soliman H, Mediavilla-Varela M, Antonia S. Indoleamine 2,3-dioxygenase： is it an immune suppressor? Cancer J. 2010；16(4)：354-359.
30.Prendergast GC, Malachowski WP, DuHadaway JB, et al. Discovery of IDO1 Inhibitors： from bench to bedside. Cancer Res. 2017；77(24)：6795-6811.
31.Yunpeng Qi RW, Liang Zhao,Lei Lv,et al. Celastrol suppresses tryptophan catabolism in human colon cancer cells as revealed by metabolic profiling and targeted metabolite analysis. Biol Pharm Bull. 2018；41：1243-1250.
32.Hu Y, Chen X, Xu Y, et al. Hierarchical assembly of hyaluronan coated albumin nanoparticles for pancreatic cancer chemoimmunotherapy. Nanoscale. 2019；11(35)：16476-1687.
33.Spano D, Zollo M. Tumor microenvironment： a main actor in the metastasis process. Clin Exp Metastasis. 2012；29(4)：381-395.
34.Choi SY, Collins CC, Gout PW, Wang Y. Cancer-generated lactic acid： a regulatory, immunosuppressive metabolite? J Pathol. 2013；230(4)：350-355.
35.Brand A, Singer K, Koehl GE, et al. LDHA-associated lactic acid production blunts tumor immunosurveillance by T and NK cells. Cell Metab. 2016；24(5)：657-671.
36.Clevers H. At the crossroads of inflammation and cancer. Cell. 2004；118(6)：671-674.
37.Latz E, Xiao TS, Stutz A. Activation and regulation of the inflammasomes. Nat Rev Immunol. 2013；13(6)：397-411.
38.Amores-Iniesta J, Barbera-Cremades M, Martinez CM, et al. Extracellular ATP activates the NLRP3 inflammasome and is an early danger signal of skin allograft rejection. Cell Rep. 2017；21(12)：3414-3426.
39.Lee HE, Lee JY, Yang G, et al. Inhibition of NLRP3 inflammasome in tumor microenvironment leads to suppression of metastatic potential of cancer cells. Sci Rep. 2019；9(1)：12277.
40.Qu D WL, Qin Y,Guo M,et al. Non-triggered sequential-release liposomes enhance anti-breast cancer efficacy of STS and celastrol-based microemulsion. Biomater Sci. 2018；6(12)：3284-3299.
41.Liu Q, Chen F, Hou L, et al. Nanocarrier-mediated chemo-immunotherapy arrested cancer progression and induced tumor dormancy in desmoplastic melanoma. ACS Nano. 2018；12(8)：7812-7825.
42.Carbonaro M, Grant G. Absorption of quercetin and rutin in rat small intestine. Ann Nutr Metab. 2005；49(3)：178-182.
43.Trinh HT, Joh EH, Kwak HY, et al. Anti-pruritic effect of baicalin and its metabolites, baicalein and oroxylin A, in mice. Acta Pharmacol Sin. 2010；31(6)：718-724.
44.Le Chatelier E, Nielsen T, Qin J, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013；500(7464)：541-546.
45.张婷,王义坤, 赵琦,等. 基于UPLC-Q-TOF-MS的雷公藤红素的代谢组学研究. 中国中药杂志. 2019；44(16)：3562-3568.
46.Ganapathy A， Subramenium SS, Jonathan S. et al. Enterotoxigenic Escherichia coli heat labile enterotoxin inhibits intestinal ascorbic acid uptake via a cAMP-dependent NF-κB-mediated pathway. Am J Physiol Gastrointest Liver Physiol 2019；316(1)：G55-G63.
47.胡维岳. 雷公藤红素对大鼠肥胖的治疗作用及机制研究. 南京医科大学. 2018.