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Current Medicinal Chemistry

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ISSN (Online): 1875-533X

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Review Article

Exploring Cantharidin and its Analogues as Anticancer Agents: A Review

Author(s): Shaoting Li, Xufeng Wu, Gang Fan, Kui Du* and Liping Deng*

Volume 30, Issue 18, 2023

Published on: 27 December, 2022

Page: [2006 - 2019] Pages: 14

DOI: 10.2174/0929867330666221103151537

Price: $65

Abstract

Background: Cantharidin (CTD) is a highly toxic substance which can be used to treat a variety of cancers. However, the clinical application of CTD is restricted due to the serious side effects. In recent years, screening its analogues, exploring the mechanism of action and using combinatory therapy with certain substances are considered to be feasible methods which can reduce side effects and improve the therapeutic activity of CTD. This review aims to describe SAR (structure-activity relationship) of CTD analogues, CTD induction mechanisms, and combinatory therapy exploration.

Methods: We searched for research about CTD by entering the database. Important information was screened and extracted purposefully, including SAR, mechanisms, methods, etc. Finally, these contents were unified into a framework to form a review.

Results: Some CTD analogues with imidazolium salt or double bonds at C-5 and C-6 positions demonstrate good anticancer activity. Through introducing methyl and acetoxy groups at the C-1 or C-4 position, the inhibitory effect of PP was weakened or even inactivated. Removing the two methyl groups of C-2 and C-3 can reduce side effects and improve efficacy. Replacing methyl with fluorine can also improve the activity and reduce toxicity. Water solubility and bioavailability could be improved by opening the five fivemembered anhydride ring to form carboxylic acid, salt, amide, and ester derivatives. The anticancer mechanism can be divided into the following aspects, including inhibiting cell invasion and metastasis, inducing apoptosis, regulating cell cycle and enhancing immunity. The proper formulation of CTD and its analogues (liposomes, nanoparticles and micelles) can improve the targeting of liver cancer and reduce toxic and side effects. CTD combined with anti-angiogenic therapeutics (Ginsenoside Rg3, Bevacizumab, Apatinib and Endostar) showed additive anti-pancreatic cancer effects.

Conclusion: It was found that the potential mechanism was closely related to multi-channel and multi-target interactions, which provided a guiding direction for the later exploration of new clinical therapeutic applications. However, some detailed mechanisms are still unclear, and more evidence is required to verify. In addition, the new methods to improve the therapeutic potential of CTD and its analogues still need more clinical trials to be tested in the future. This prospect is very broad and worthy of further study.

Keywords: Cantharidin, toxicity, anticancer, side effects, structure-activity relationship, combined therapy.

« Previous Next »
[1]
Yao, H.; Zhao, J.; Wang, Z.; Lv, J.; Du, G.; Jin, Y.; Zhang, Y.; Song, S.; Han, G. Enhanced anticancer efficacy of cantharidin by mPEG-PLGA micellar encapsulation: An effective strategy for application of a poisonous traditional Chinese medicine. Colloids Surf. B Biointerfaces, 2020, 196, 111285.
[http://dx.doi.org/10.1016/j.colsurfb.2020.111285] [PMID: 32771818]
[2]
Chattopadhyay, D.; Swingle, M.R.; Salter, E.A.; Wood, E.; D’Arcy, B.; Zivanov, C.; Abney, K.; Musiyenko, A.; Rusin, S.F.; Kettenbach, A.; Yet, L.; Schroeder, C.E.; Golden, J.E.; Dunham, W.H.; Gingras, A.C.; Banerjee, S.; Forbes, D.; Wierzbicki, A.; Honkanen, R.E. Crystal structures and mutagenesis of PPP-family ser/thr protein phosphatases elucidate the selectivity of cantharidin and novel norcantharidin-based inhibitors of PP5C. Biochem. Pharmacol., 2016, 109, 14-26.
[http://dx.doi.org/10.1016/j.bcp.2016.03.011] [PMID: 27002182]
[3]
Ghoneim, K. Cantharidin toxicosis to animal and human in the world: A review. Stand. Res. J. Toxicol. Environ. Health Sci., 2013, 2013, 43229799.
[4]
Jakovac-Strajn, B.; Brozić, D.; Tavčar-Kalcher, G.; Babič, J.; Trilar, T.; Vengust, M. Entomological surveillance and cantharidin concentrations in Mylabris variabilis and Epicauta rufidorsum blister beetles in slovenia. Animals, 2021, 11(1), 220-228.
[http://dx.doi.org/10.3390/ani11010220] [PMID: 33477415]
[5]
Yi, S.; Wass, J.; Vincent, P.; Iland, H. Inhibitory effect of norcantharidin on K562 human myeloid leukemia cells in vitro. Leuk. Res., 1991, 15(10), 883-886.
[http://dx.doi.org/10.1016/0145-2126(91)90163-N] [PMID: 1921448]
[6]
Falck, B. Spanish Fly—Cantharidin’s Alter Ego. JAMA Dermatol., 2018, 154(1), 51-51.
[http://dx.doi.org/10.1001/jamadermatol.2017.4531] [PMID: 29322194]
[7]
Gisondi, S.; Gasperi, T.; Roma, E.; Tomai, P.; Gentili, A.; Vignoli, L.; Bologna, M.A.; Mancini, E. Cantharidin content in two Mediterranean species of blister beetles, Lydus trimaculatus and Mylabris variabilis (Coleoptera: Meloidae). Entomol. Sci., 2019, 22(3), 258-263.
[http://dx.doi.org/10.1111/ens.12364]
[8]
Wang, S.; Wu, X.; Tan, M.; Gong, J.; Tan, W.; Bian, B.; Chen, M.; Wang, Y. Fighting fire with fire: Poisonous Chinese herbal medicine for cancer therapy. J. Ethnopharmacol., 2012, 140(1), 33-45.
[http://dx.doi.org/10.1016/j.jep.2011.12.041] [PMID: 22265747]
[9]
Eichenfield, L.F.; McFalda, W.; Brabec, B.; Siegfried, E.; Kwong, P.; McBride, M.; Rieger, J.; Willson, C.; Davidson, M.; Burnett, P. Safety and efficacy of VP-102, a proprietary, drug-device combination product containing cantharidin, 0.7% (w/v), in children and adults with molluscum contagiosum. JAMA Dermatol., 2020, 156(12), 1315-1323.
[http://dx.doi.org/10.1001/jamadermatol.2020.3238] [PMID: 32965495]
[10]
Pan, M.S.; Cao, J.; Fan, Y.Z. Insight into norcantharidin, a small-molecule synthetic compound with potential multi- target anticancer activities. Chin. Med., 2020, 15(1), 55-82.
[http://dx.doi.org/10.1186/s13020-020-00338-6] [PMID: 32514288]
[11]
Jiang, Z.; Chi, J.; Han, B.; Liu, W. Preparation and pharmacological evaluation of norcantharidin-conjugated carboxymethyl chitosan in mice bearing hepatocellular carcinoma. Carbohydr. Polym., 2017, 174, 282-290.
[http://dx.doi.org/10.1016/j.carbpol.2017.06.072] [PMID: 28821069]
[12]
Liu, D. W.; Chen, Z. W. The effects of cantharidin and cantharidin derivates on tumour cells. Anti-Cancer Agent Med., 2009, 9(4), 392-396.
[13]
Deng, L.P.; Dong, J.; Cai, H.; Wang, W. Cantharidin as an antitumor agent: A retrospective review. Curr. Med. Chem., 2013, 20(2), 159-166.
[http://dx.doi.org/10.2174/092986713804806711] [PMID: 23210849]
[14]
Ren, Y.; Kinghorn, A.D. Antitumor potential of the protein phosphatase inhibitor, cantharidin, and selected derivatives. Bioorg. Med. Chem., 2021, 32, 116012.
[http://dx.doi.org/10.1016/j.bmc.2021.116012] [PMID: 33454654]
[15]
Ma, Q.; Feng, Y.; Deng, K.; Shao, H.; Sui, T.; Zhang, X.; Sun, X.; Jin, L.; Ma, Z.; Luo, G. Unique responses of hepatocellular carcinoma and cholangiocarcinoma cell lines toward cantharidin and norcantharidin. J. Cancer, 2018, 9(12), 2183-2190.
[http://dx.doi.org/10.7150/jca.25454] [PMID: 29937938]
[16]
Su, C.C.; Liu, S.H.; Lee, K.I.; Huang, K.T.; Lu, T.H.; Fang, K.M.; Wu, C.C.; Yen, C.C.; Lai, C.H.; Su, Y.C.; Huang, C.F. Cantharidin induces apoptosis through the calcium/PKC-regulated endoplasmic reticulum stress pathway in human bladder cancer cells. Am. J. Chin. Med., 2015, 43(3), 581-600.
[http://dx.doi.org/10.1142/S0192415X15500366] [PMID: 25967669]
[17]
Kuo, J-H.; Chu, Y-L.; Yang, J-S.; Lin, J-P.; Lai, K-C.; Kuo, H-M.; Hsia, T-C.; Chung, J-G. Cantharidin induces apoptosis in human bladder cancer TSGH 8301 cells through mitochondria-dependent signal pathways. Int. J. Oncol., 2010, 37(5), 1243-1250.
[PMID: 20878071]
[18]
Zhang, Q.; Zhu, G. The pathological pattern of seven malignant cancers following Demethylcantharidin. Adv. Pharm. J., 2017, 2(6), 243-247.
[19]
Yeh, C.B.; Hsieh, M.J.; Hsieh, Y.H.; Chien, M.H.; Chiou, H.L.; Yang, S.F. Antimetastatic effects of norcantharidin on hepatocellular carcinoma by transcriptional inhibition of MMP-9 through modulation of NF-kB activity. PLoS One, 2012, 7(2), e31055.
[http://dx.doi.org/10.1371/journal.pone.0031055] [PMID: 22363545]
[20]
Wang, G.S. Medical uses of mylabris in ancient China and recent studies. J. Ethnopharmacol., 1989, 26(2), 147-162.
[http://dx.doi.org/10.1016/0378-8741(89)90062-7] [PMID: 2689797]
[21]
Wang, G.; Dong, J.; Deng, L. Overview of cantharidin and its analogues. Curr. Med. Chem., 2018, 25(17), 2034-2044.
[http://dx.doi.org/10.2174/0929867324666170414165253] [PMID: 28413963]
[22]
Wang, G.F. The new developments of cantharidin and its analogues. J. Chem. Soc. Pak., 2017, 39(4), 599-609.
[23]
Millán, A.P.; Torres, J.J.; Johnson, S.; Marro, J. Growth strategy determines the memory and structural properties of brain networks. Neural Netw., 2021, 142, 44-56.
[http://dx.doi.org/10.1016/j.neunet.2021.04.027] [PMID: 33984735]
[24]
McCluskey, A.; Bowyer, M.C.; Collins, E.; Sim, A.T.R.; Sakoff, J.A.; Baldwin, M.L. Anhydride modified cantharidin analogues: Synthesis, inhibition of protein phosphatases 1 and 2A and anticancer activity. Bioorg. Med. Chem. Lett., 2000, 10(15), 1687-1690.
[http://dx.doi.org/10.1016/S0960-894X(00)00323-1] [PMID: 10937725]
[25]
Hizartzidis, L.; Gilbert, J.; Gordon, C.P.; Sakoff, J.A.; McCluskey, A. Synthesis and cytotoxicity of octahydroepoxyisoindole-7-carboxylic acids and norcantharidin–amide hybrids as norcantharidin analogues. ChemMedChem, 2019, 14(12), 1152-1161.
[http://dx.doi.org/10.1002/cmdc.201900180] [PMID: 30938091]
[26]
Li, Y.; Sun, H.; Xi, N.; Zhang, Y. Effects of cantharidin and norcantharidin on larval feeding and adult oviposition preferences of the Diamondback Moth (Lepidoptera: Plutellidae). J. Econ. Entomol., 2019, 112(4), 1634-1637.
[http://dx.doi.org/10.1093/jee/toz049] [PMID: 30924494]
[27]
Wang, L.; Zheng, S.L.; Lv, S.M.; Zhang, Y.L.; Wang, Y. Inhibitory mechanism of cantharidin derivatives against Sclerotinia sclerotiorum. Chinese J. Pesticide Sci., 2021, 23(1), 107-116.
[28]
Massicot, F.; Dutertre-Catella, H.; Pham-Huy, C.; Liu, X.H.; Duc, H.T.; Warnet, J.M. In vitro assessment of renal toxicity and inflammatory events of two protein phosphatase inhibitors cantharidin and nor-cantharidin. Basic Clin. Pharmacol. Toxicol., 2005, 96(1), 26-32.
[http://dx.doi.org/10.1111/j.1742-7843.2005.pto960104.x] [PMID: 15667592]
[29]
Zhao, C.; Jia, J.; Wang, X.; Luo, C.; Wang, Y. Synthesis of norcantharidin complex salts. J. Heterocycl. Chem., 2019, 56(5), 1567-1570.
[http://dx.doi.org/10.1002/jhet.3533]
[30]
Xiao, Z.; Wen, L.; Zeng, D.; Yin, D.; Zhou, X.; Tang, C.; Li, Y. Protein phosphatase 2A inhibiting β-catenin phosphorylation contributes critically to the anti-renal interstitial fibrotic effect of norcantharidin. Inflammation, 2020, 43(3), 878-891.
[http://dx.doi.org/10.1007/s10753-019-01173-0] [PMID: 31940108]
[31]
Essers, M.; Wibbeling, B.; Haufe, G. Synthesis of the first fluorinated cantharidin analogues. Tetrahedron Lett., 2001, 42(32), 5429-5433.
[http://dx.doi.org/10.1016/S0040-4039(01)01056-5]
[32]
McCluskey, A.; Taylor, C.; Quinn, R.J.; Suganuma, M.; Fujiki, H. Inhibition of protein phosphatase 2A by cantharidin analogues. Bioorg. Med. Chem. Lett., 1996, 6(9), 1025-1028.
[http://dx.doi.org/10.1016/0960-894X(96)00166-7]
[33]
Baba, Y.; Hirukawa, N.; Tanohira, N.; Sodeoka, M. Structure-based design of a highly selective catalytic site-directed inhibitor of Ser/Thr protein phosphatase 2B (calcineurin). J. Am. Chem. Soc., 2003, 125(32), 9740-9749.
[http://dx.doi.org/10.1021/ja034694y] [PMID: 12904040]
[34]
Thaqi, A.; Scott, J.L.; Gilbert, J.; Sakoff, J.A.; McCluskey, A. Synthesis and biological activity of Δ-5,6-norcantharimides: Importance of the 5,6-bridge. Eur. J. Med. Chem., 2010, 45(5), 1717-1723.
[http://dx.doi.org/10.1016/j.ejmech.2010.01.004] [PMID: 20153915]
[35]
Manda, S.; Sharma, S.; Wani, A.; Joshi, P.; Kumar, V.; Guru, S.K.; Bharate, S.S.; Bhushan, S.; Vishwakarma, R.A.; Kumar, A.; Bharate, S.B. Discovery of a marine-derived bis-indole alkaloid fascaplysin, as a new class of potent P-glycoprotein inducer and establishment of its structure–activity relationship. Eur. J. Med. Chem., 2016, 107, 1-11.
[http://dx.doi.org/10.1016/j.ejmech.2015.10.049] [PMID: 26560048]
[36]
Sun, R.R.; Guo, J.H.; Yang, C.; Yang, L.J.; Huang, C. Synthesis and antitumor evaluation of novel N-substituted norcantharidin imidazolium derivatives. Curr. Org. Synth., 2018, 15(2), 237-245.
[http://dx.doi.org/10.2174/1570179414666170824160901]
[37]
Deng, L.; Dong, J.; Wang, W. Exploiting protein phosphatase inhibitors based on cantharidin analogues for cancer drug discovery. Mini Rev. Med. Chem., 2013, 13(8), 1166-1176.
[http://dx.doi.org/10.2174/1389557511313080005] [PMID: 23373656]
[38]
Deng, L.; Tang, S. Norcantharidin analogues: A patent review (2006 – 2010). Expert Opin. Ther. Pat., 2011, 21(11), 1743-1753.
[http://dx.doi.org/10.1517/13543776.2011.629190] [PMID: 22017412]
[39]
McCluskey, A.; Keane, M.A.; Mudgee, L.M.; Sim, A.T.R.; Sakoff, J.; Quinn, R.J. Anhydride modified cantharidin analogues. Is ring opening important in the inhibition of protein phosphatase 2A? Eur. J. Med. Chem., 2000, 35(10), 957-964.
[http://dx.doi.org/10.1016/S0223-5234(00)00186-0] [PMID: 11121622]
[40]
Pachuta-Stec, A.; Nowak, R.; Pietrzak, W.; Pitucha, M. Synthesis and antioxidant activity of new norcantharidin analogs. Chem. Biodivers., 2019, 16(4), e1800673.
[http://dx.doi.org/10.1002/cbdv.201800673] [PMID: 30888741]
[41]
Lawrenson, S.B.; Pearce, A.K.; Hart, S.; Whitwood, A.C.; O’Reilly, R.K.; North, M. Synthesis of cytotoxic spirocyclic imides from a biomass-derived oxanorbornene. Tetrahedron, 2021, 77, 131754.
[http://dx.doi.org/10.1016/j.tet.2020.131754]
[42]
He, T.; Liu, J.; Wang, X.; Duan, C.; Li, X.; Zhang, J. Analysis of cantharidin-induced nephrotoxicity in HK-2 cells using untargeted metabolomics and an integrative network pharmacology analysis. Food Chem. Toxicol., 2020, 146, 111845.
[http://dx.doi.org/10.1016/j.fct.2020.111845] [PMID: 33152469]
[43]
He, T.; Wang, Q.; Ao, J.; Chen, K.; Li, X.; Zhang, J.; Duan, C. Endoplasmic reticulum stress contributes to autophagy and apoptosis in cantharidin-induced nephrotoxicity. Food Chem. Toxicol., 2022, 163, 112986.
[http://dx.doi.org/10.1016/j.fct.2022.112986] [PMID: 35398186]
[44]
Yu, Y.; Zhang, Y.; Zhang, J.; Guan, C.; Liu, L.; Ren, L. Cantharidin-induced acute hepatotoxicity: The role of TNF-α, IKK-α, Bcl-2, Bax and caspase3. J. Appl. Toxicol., 2020, 40(11), 1526-1533.
[http://dx.doi.org/10.1002/jat.4003] [PMID: 32627230]
[45]
Zhang, J.; Chen, Q.; Wang, L.; Chen, K.; Mu, W.; Duan, C.; Li, X. Study on the mechanism of cantharidin-induced hepatotoxicity in rat using serum and liver metabolomics combined with conventional pathology methods. J. Appl. Toxicol., 2020, 40(9), 1259-1271.
[http://dx.doi.org/10.1002/jat.3983] [PMID: 32468647]
[46]
Liu, F.; Wang, X.; Duan, C.; Zhang, J.; Li, X. Hepatoxicity mechanism of cantharidin-induced liver LO2 cells by LC–MS metabolomics combined traditional approaches. Toxicol. Lett., 2020, 333, 49-61.
[http://dx.doi.org/10.1016/j.toxlet.2020.07.024] [PMID: 32726682]
[47]
Zhang, X.; Lin, C.C.; Chan, W.K.N.; Liu, K.L.; Yang, Z.J.; Zhang, H.Q. Augmented anticancer effects of cantharidin with liposomal encapsulation: In vitro and in vivo evaluation. Molecules, 2017, 22(7), 1052-1063.
[http://dx.doi.org/10.3390/molecules22071052] [PMID: 28672816]
[48]
Naz, F.; Wu, Y.; Zhang, N.; Yang, Z.; Yu, C. Anticancer attributes of cantharidin: Involved molecular mechanisms and pathways. Molecules, 2020, 25(14), 3279-3297.
[http://dx.doi.org/10.3390/molecules25143279] [PMID: 32707651]
[49]
Cohen, A.; Ioannidis, K.; Ehrlich, A.; Regenbaum, S.; Cohen, M.; Ayyash, M.; Tikva, S.S.; Nahmias, Y. Mechanism and reversal of drug-induced nephrotoxicity on a chip. Sci. Transl. Med., 2021, 13(582), eabd6299.
[http://dx.doi.org/10.1126/scitranslmed.abd6299] [PMID: 33627489]
[50]
Su, R.; Wu, H.; Liu, X.; Wei, L. Predicting drug-induced hepatotoxicity based on biological feature maps and diverse classification strategies. Brief. Bioinform., 2021, 22(1), 428-437.
[http://dx.doi.org/10.1093/bib/bbz165] [PMID: 31838506]
[51]
Yu, Z.; Li, L.; Wang, C.; He, H.; Liu, G.; Ma, H.; Pang, L.; Jiang, M.; Lu, Q.; Li, P.; Qi, H. Cantharidin induces apoptosis and promotes differentiation of AML cells through nuclear receptor Nur77-mediated signaling pathway. Front. Pharmacol., 2020, 11, 1321.
[http://dx.doi.org/10.3389/fphar.2020.01321] [PMID: 32982739]
[52]
Zhu, M.; Shi, X.; Gong, Z.; Su, Q.; Yu, R.; Wang, B.; Yang, T.; Dai, B.; Zhan, Y.; Zhang, D.; Zhang, Y. Cantharidin treatment inhibits hepatocellular carcinoma development by regulating the JAK2/STAT3 and PI3K/Akt pathways in an EphB4-dependent manner. Pharmacol. Res., 2020, 158, 104868.
[http://dx.doi.org/10.1016/j.phrs.2020.104868] [PMID: 32407961]
[53]
Song, M.; Wang, X.; Luo, Y.; Liu, Z.; Tan, W.; Ye, P.; Fu, Z.; Lu, F.; Xiang, W.; Tang, L.; Yao, L.; Nie, Y.; Xiao, J. Cantharidin suppresses gastric cancer cell migration/invasion by inhibiting the PI3K/Akt signaling pathway via CCAT1. Chem. Biol. Interact., 2020, 317, 108939.
[http://dx.doi.org/10.1016/j.cbi.2020.108939] [PMID: 31945315]
[54]
Wang, J.; Gong, J.; Wei, Z. Strategies for liposome drug delivery systems to improve tumor treatment efficacy. AAPS PharmSciTech, 2022, 23(1), 27.
[http://dx.doi.org/10.1208/s12249-021-02179-4] [PMID: 34907483]
[55]
Zhu, K.; Zhou, L.; Zou, M.; Ning, S.; Liu, S.; Zhou, Y.; Du, K.; Zhang, X.; Xia, X. 18-GA-Suc modified liposome loading cantharidin for augmenting hepatic specificity: Preparation, characterization, antitumor effects, and liver-targeting efficiency. J. Pharm. Sci., 2020, 109(6), 2038-2047.
[http://dx.doi.org/10.1016/j.xphs.2020.03.001] [PMID: 32173319]
[56]
Zhou, L.; Zou, M.; Zhu, K.; Ning, S.; Xia, X. Development of 11-DGA-3-O-gal-modified cantharidin liposomes for treatment of Hepatocellular carcinoma. Molecules, 2019, 24(17), 3080-3098.
[http://dx.doi.org/10.3390/molecules24173080] [PMID: 31450608]
[57]
Zhu, J.; Zhang, W.; Wang, D.; Li, S.; Wu, W. Preparation and characterization of norcantharidin liposomes modified with stearyl glycyrrhetinate. Exp. Ther. Med., 2018, 16(3), 1639-1646.
[http://dx.doi.org/10.3892/etm.2018.6416] [PMID: 30186382]
[58]
Liu, Y. Phase 1 clinical study for evaluation of pharmacokinetic, safety, tolerance of Norcantharidin lipid microsphere for injection in patients with solid tumor, NCT04673396, 2020. https://clinicaltrials.gov/ct2/show/NCT04673396.
[59]
Zhang, H.; Jiang, Y.; Ni, X.; Chen, L.; Wu, M.; Liu, J.; Yang, B.; Shan, X.; Yang, L.; Fan, J.; Chen, Y.; Wu, J.; Fu, S. Glycyrrhetinic acid-modified norcantharidin nanoparticles for active targeted therapy of Hepatocellular carcinoma. J. Biomed. Nanotechnol., 2018, 14(1), 114-126.
[http://dx.doi.org/10.1166/jbn.2018.2467] [PMID: 29463369]
[60]
Huang, X.; Tang, W.; Lin, C.; Sa, Z.; Xu, M.; Liu, J.; Wang, L.; Li, W.; Chen, Y.; Yang, C. Protective mechanism of Astragalus polysaccharides against Cantharidin-induced liver injury determined in vivo by liquid chromatography/mass spectrometry metabolomics. Basic Clin. Pharmacol. Toxicol., 2021, 129(1), 61-71.
[http://dx.doi.org/10.1111/bcpt.13585] [PMID: 33834601]
[61]
Shao, H.; Dong, L.; Feng, Y.; Wang, C.; Tong, H. The protective effect of L-glutamine against acute cantharidin-induced cardiotoxicity in the mice. BMC Pharmacol. Toxicol., 2020, 21(1), 71-80.
[http://dx.doi.org/10.1186/s40360-020-00449-8] [PMID: 33004081]
[62]
Du, Y.; Wan, H.; Huang, P.; Yang, J.; He, Y. A critical review of Astragalus polysaccharides: From therapeutic mechanisms to pharmaceutics. Biomed. Pharmacother., 2022, 147, 112654.
[http://dx.doi.org/10.1016/j.biopha.2022.112654] [PMID: 35086031]
[63]
Singh, R.; Cheng, S.; Li, J.; Kumar, S.; Zeng, Q.; Zeng, Q. Norcantharidin combined with 2-deoxy-d-glucose suppresses the hepatocellular carcinoma cells proliferation and migration. 3 Biotech, 2021, 11(3), 142-154.
[64]
Xu, M.D.; Liu, L.; Wu, M.Y.; Jiang, M.; Shou, L.M.; Wang, W.J.; Wu, J.; Zhang, Y.; Gong, F.R.; Chen, K.; Tao, M.; Zhi, Q.; Li, W. The combination of cantharidin and antiangiogenic therapeutics presents additive antitumor effects against pancreatic cancer. Oncogenesis, 2018, 7(11), 94-108.
[http://dx.doi.org/10.1038/s41389-018-0102-2] [PMID: 30478299]

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