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Mini-Reviews in Medicinal Chemistry

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ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

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Review Article

Alkaloids Exhibit a Meaningful Function as Anticancer Agents by Restraining Cellular Signaling Pathways

Author(s): Wen Xu, Bei Wang, Yisong Gao, Yuxuan Cai, Jiali Zhang, Zhiyin Wu, Jiameng Wei, Chong Guo* and Chengfu Yuan*

Volume 22, Issue 7, 2022

Published on: 06 January, 2022

Page: [968 - 983] Pages: 16

DOI: 10.2174/1389557521666211007114935

Price: $65

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Abstract

Alkaloids are nitrogen-containing organic compounds widely found in natural products, which play an essential role in clinical treatment. Cellular signaling pathways in tumors are a series of enzymatic reaction pathways that convert extracellular signals into intracellular signals to produce biological effects. The ordered function of cell signaling pathways is essential for tumor cell proliferation, differentiation, and programmed death. This review describes the antitumor progression mediated by various alkaloids after inhibiting classical signaling pathways; related studies are systematically retrieved and collected through PubMed. We selected the four currently most popular pathways for discussion and introduced the molecular mechanisms mediated by alkaloids in different signaling pathways, including the NF-kB signaling pathway, PI3K/AKT signaling pathway, MAPK signaling pathway, and P53 signaling pathway. The research progress of alkaloids related to tumor signal transduction pathways and the realization of alkaloids as cancer prevention drugs by targeting signal pathways remains.

Keywords: Alkaloids, anti-cancer, signaling pathway, clinical treatment, natural products, NF- kB signaling pathway.

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[1]
F.P.J.A.r.o.p, Z.J. Alkaloid biosynthesis: Metabolism and trafficking. Biology, 2008, 59, 735-769.
[2]
Disis, M.L. Immune regulation of cancer. J. Clin. Oncol., 2010, 28(29), 4531-4538.
[http://dx.doi.org/10.1200/JCO.2009.27.2146] [PMID: 20516428]
[3]
Dunn, G.P.; Old, L.J.; Schreiber, R.D. The three Es of cancer immunoediting. Annu. Rev. Immunol., 2004, 22, 329-360.
[http://dx.doi.org/10.1146/annurev.immunol.22.012703.104803] [PMID: 15032581]
[4]
Guttridge, D.C.; Albanese, C.; Reuther, J.Y.; Pestell, R.G.; Baldwin, A.S. Jr NF-kappaB controls cell growth and differentiation through transcriptional regulation of cyclin D1. Mol. Cell. Biol., 1999, 19(8), 5785-5799.
[http://dx.doi.org/10.1128/MCB.19.8.5785] [PMID: 10409765]
[5]
La Rosa, F.A.; Pierce, J.W.; Sonenshein, G.E. Differential regulation of the c-myc oncogene promoter by the NF-kappa B rel family of transcription factors. Mol. Cell. Biol., 1994, 14(2), 1039-1044.
[http://dx.doi.org/10.1128/MCB.14.2.1039] [PMID: 8289784]
[6]
Perkins, N.D. Achieving transcriptional specificity with NF-kappa B. Int. J. Biochem. Cell Biol., 1997, 29(12), 1433-1448.
[http://dx.doi.org/10.1016/S1357-2725(97)00088-5] [PMID: 9570137]
[7]
Huber, M.A.; Azoitei, N.; Baumann, B.; Grünert, S.; Sommer, A.; Pehamberger, H.; Kraut, N.; Beug, H.; Wirth, T. NF-kappaB is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression. J. Clin. Invest., 2004, 114(4), 569-581.
[http://dx.doi.org/10.1172/JCI200421358] [PMID: 15314694]
[8]
Fresno Vara, J.A.; Casado, E.; de Castro, J.; Cejas, P.; Belda-Iniesta, C.; González-Barón, M. PI3K/Akt signalling pathway and cancer. Cancer Treat. Rev., 2004, 30(2), 193-204.
[http://dx.doi.org/10.1016/j.ctrv.2003.07.007] [PMID: 15023437]
[9]
Li, T.; Wang, G. Computer-aided targeting of the PI3K/Akt/mTOR pathway: Toxicity reduction and therapeutic opportunities. Int. J. Mol. Sci., 2014, 15(10), 18856-18891.
[http://dx.doi.org/10.3390/ijms151018856] [PMID: 25334061]
[10]
Carpenter, R.L.; Jiang, B.H. Roles of EGFR, PI3K, AKT, and mTOR in heavy metal-induced cancer. Curr. Cancer Drug Targets, 2013, 13(3), 252-266.
[http://dx.doi.org/10.2174/1568009611313030004] [PMID: 23297824]
[11]
Torii, S.; Yamamoto, T.; Tsuchiya, Y.; Nishida, E. ERK MAP kinase in G cell cycle progression and cancer. Cancer Sci., 2006, 97(8), 697-702.
[http://dx.doi.org/10.1111/j.1349-7006.2006.00244.x] [PMID: 16800820]
[12]
Dhillon, A.S.; Hagan, S.; Rath, O.; Kolch, W. MAP kinase signalling pathways in cancer. Oncogene, 2007, 26(22), 3279-3290.
[http://dx.doi.org/10.1038/sj.onc.1210421] [PMID: 17496922]
[13]
McCubrey, J.A.; Lahair, M.M.; Franklin, R.A. Reactive oxygen species-induced activation of the MAP kinase signaling pathways. Antioxid. Redox Signal., 2006, 8(9-10), 1775-1789.
[http://dx.doi.org/10.1089/ars.2006.8.1775] [PMID: 16987031]
[14]
Schubbert, S.; Shannon, K.; Bollag, G. Hyperactive Ras in developmental disorders and cancer. Nat. Rev. Cancer, 2007, 7(4), 295-308.
[http://dx.doi.org/10.1038/nrc2109] [PMID: 17384584]
[15]
Halilovic, E.; Solit, D.B. Therapeutic strategies for inhibiting oncogenic BRAF signaling. Curr. Opin. Pharmacol., 2008, 8(4), 419-426.
[http://dx.doi.org/10.1016/j.coph.2008.06.014] [PMID: 18644254]
[16]
Zebisch, A.; Staber, P.B.; Delavar, A.; Bodner, C.; Hiden, K.; Fischereder, K.; Janakiraman, M.; Linkesch, W.; Auner, H.W.; Emberger, W.; Windpassinger, C.; Schimek, M.G.; Hoefler, G.; Troppmair, J.; Sill, H. Two transforming C-RAF germ-line mutations identified in patients with therapy-related acute myeloid leukemia. Cancer Res., 2006, 66(7), 3401-3408.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-0115] [PMID: 16585161]
[17]
Huang, C.; Jacobson, K.; Schaller, M.D. MAP kinases and cell migration. J. Cell Sci., 2004, 117(Pt 20), 4619-4628.
[http://dx.doi.org/10.1242/jcs.01481] [PMID: 15371522]
[18]
Chakraborti, S.; Mandal, M.; Das, S.; Mandal, A.; Chakraborti, T. Regulation of matrix metalloproteinases: An overview. Mol. Cell. Biochem., 2003, 253(1-2), 269-285.
[http://dx.doi.org/10.1023/A:1026028303196] [PMID: 14619979]
[19]
Balmanno, K.; Cook, S.J. Tumour cell survival signalling by the ERK1/2 pathway. Cell Death Differ., 2009, 16(3), 368-377.
[http://dx.doi.org/10.1038/cdd.2008.148] [PMID: 18846109]
[20]
Warr, M.R.; Shore, G.C. Unique biology of Mcl-1: Therapeutic opportunities in cancer. Curr. Mol. Med., 2008, 8(2), 138-147.
[http://dx.doi.org/10.2174/156652408783769580] [PMID: 18336294]
[21]
Vousden, K.H.; Prives, C. Blinded by the light: The growing complexity of p53. Cell, 2009, 137(3), 413-431.
[http://dx.doi.org/10.1016/j.cell.2009.04.037] [PMID: 19410540]
[22]
Zhao, X.; Shen, J.; Chang, K.J.; Kim, S.H. Comparative analysis of antioxidant activity and functional components of the ethanol extract of lotus (Nelumbo nucifera) from various growing regions. J. Agric. Food Chem., 2014, 62(26), 6227-6235.
[http://dx.doi.org/10.1021/jf501644t] [PMID: 24932940]
[23]
C. SH. J. IH, C. DH, O. JW, A.Y.J.J.o. Growth-inhibiting effects of Coptis japonica root-derived isoquinoline alkaloids on human intestinal bacteria. Agri. Food Chem., 1999, 47, 934-938.
[24]
Altinoz, M.A.; Topcu, G.; Hacimuftuoglu, A.; Ozpinar, A.; Ozpinar, A.; Hacker, E.; Elmaci, İ. Noscapine, a non-addictive opioid and microtubule-inhibitor in potential treatment of glioblastoma. Neurochem. Res., 2019, 44(8), 1796-1806.
[http://dx.doi.org/10.1007/s11064-019-02837-x] [PMID: 31292803]
[25]
Sverrisdóttir, E.; Lund, T.M.; Olesen, A.E.; Drewes, A.M.; Christrup, L.L.; Kreilgaard, M. A review of morphine and morphine-6-glucuronide’s pharmacokinetic-pharmacodynamic relationships in experimental and clinical pain. Eur. J. Pharm. Sci., 2015, 74, 45-62.
[http://dx.doi.org/10.1016/j.ejps.2015.03.020] [PMID: 25861720]
[26]
Li, M.; Liu, G.; Wang, K.; Wang, L.; Fu, X.; Lim, L.Y.; Chen, W.; Mo, J. Metal ion-responsive nanocarrier derived from phosphonated calix[4]arenes for delivering dauricine specifically to sites of brain injury in a mouse model of intracerebral hemorrhage. J. Nanobiotechnology, 2020, 18(1), 61.
[http://dx.doi.org/10.1186/s12951-020-00616-3] [PMID: 32306970]
[27]
Bao, M.; Cao, Z.; Yu, D.; Fu, S.; Zhang, G.; Yang, P.; Pan, Y.; Yang, B.; Han, H.; Zhou, Q. Columbamine suppresses the proliferation and neovascularization of metastatic osteosarcoma U2OS cells with low cytotoxicity. Toxicol. Lett., 2012, 215(3), 174-180.
[http://dx.doi.org/10.1016/j.toxlet.2012.10.015] [PMID: 23124089]
[28]
Chao, M.W.; Lai, M.J.; Liou, J.P.; Chang, Y.L.; Wang, J.C.; Pan, S.L.; Teng, C.M. The synergic effect of vincristine and vorinostat in leukemia In Vitro and in vivo. J. Hematol. Oncol., 2015, 8, 82.
[http://dx.doi.org/10.1186/s13045-015-0176-7] [PMID: 26156322]
[29]
Xu, H.; He, L.; Nie, S.; Guan, J.; Zhang, X.; Yang, X.; Pan, W. Optimized preparation of vinpocetine proliposomes by a novel method and in vivo evaluation of its pharmacokinetics in New Zealand rabbits. J. Control. Release, 2009, 140(1), 61-68.
[http://dx.doi.org/10.1016/j.jconrel.2009.07.014] [PMID: 19651165]
[30]
Lin, L.C.; Li, S.H.; Wu, Y.T.; Kuo, K.L.; Tsai, T.H. Pharmacokinetics and urine metabolite identification of dehydroevodiamine in the rat. J. Agric. Food Chem., 2012, 60(7), 1595-1604.
[http://dx.doi.org/10.1021/jf204365m] [PMID: 22283510]
[31]
Krajnik, G.; Wein, W.; Greil, R.; Marhold, F.; Mohn-Staudner, A.; Kummer, F.; Malayeri, R.; Zöchbauer-Müller, S.; Huber, H.; Pirker, R. Vinorelbine/gemcitabine in advanced non-small cell lung cancer (NSCLC): A phase I trial. Eur. J. Cancer, 1998, 1977-1980.
[32]
Ma, X.; Li, P.; Chen, P.; Li, J.; Huang, H.; Wang, C.; Li, W.; Ding, J.; Zhao, Y.; Yu, F.X.; Qi, X.; Zhang, L. Staurosporine targets the Hippo pathway to inhibit cell growth. J. Mol. Cell Biol., 2018, 10(3), 267-269.
[http://dx.doi.org/10.1093/jmcb/mjy016] [PMID: 29562261]
[33]
Diosa-Toro, M.; Troost, B.; Pol, D.; Heberle, A.M.; Urcuqui-Inchima, S.; Thedieck, K.; Smit, J.M. Tomatidine, a novel antiviral compound towards dengue virus. Antiviral Res., 2019, 161, 90-99.
[34]
Aziz, A.; Randhawa, M.A.; Butt, M.S.; Asghar, A.; Yasin, M.; Shibamoto, T. Glycoalkaloids (α-chaconine and α-solanine) contents of selected Pakistani potato cultivars and their dietary intake assessment. J. Food Sci., 2012, 77, T58-T61.
[35]
Ma, H.; Li, H-Q.; Zhang, X. Cyclopamine, a naturally occurring alkaloid, and its analogues may find wide applications in cancer therapy. Curr. Top. Med. Chem., 2013, 13, 2208-2215.
[36]
Fu, R.; Wang, X.; Hu, Y.; Du, H.; Dong, B.; Ao, S.; Zhang, L.; Sun, Z.; Zhang, L.; Lv, G.; Ji, J. Solamargine inhibits gastric cancer progression by regulating the expression of lncNEAT1_2 via the MAPK signaling pathway. Int. J. Oncol., 2019, 54, 1545-1554.
[37]
Elhassan, S.; Bagdas, D.; Damaj, M.I. Effects of Nicotine Metabolites on Nicotine Withdrawal Behaviors in Mice. Nicotine Tob. Res., 2017, 19, 763-766.
[38]
Krmpotic, E.; Farnsworth, N.R.; Messmer, W.M. Cryptopleurine, an active antiviral alkaloid from Boehmeria cylindrica (L.). Sw. (Urticaceae). J. Pharm. Sci., 1972, 61, 1508-1509.
[39]
Cook, D.; Gardne, D.R.; Pfister, J.A. Swainsonine-containing plants and their relationship to endophytic fungi. J. Agric. Food Chem., 2014, 62, 7326-7334.
[40]
Dong, H-J.; Wang, Z-H.; Meng, W.; Li, C-C.; Hu, Y-Z.; Zhou, L.; Wang, X-J. The natural compound homoharringtonine presents broad antiviral activity in vitro and in vivo. Viruses, 2018, 10(11), 601.
[41]
Huang, J.; Xu, H. Matrine: Bioactivities and structural modifications. Curr. Top. Med. Chem., 2016, 16, 3365-3378.
[42]
Chapa-Oliver, A.M. Mejía-Teniente. L. Capsaicin: From plants to a cancer-suppressing agent. Molecules, 2016, 21(8), 931.
[43]
Everett, P.C.; Meyers, J.A.; Makkinje, A.; Rabbi, M.; Lerner, A. Preclinical assessment of curcumin as a potential therapy for B-CLL. Am. J. Hematol., 2007, 82(1), 23-30.
[http://dx.doi.org/10.1002/ajh.20757] [PMID: 16947318]
[44]
Xu, T.; Li, D.; Zhou, X.; Ouyang, H.D.; Zhou, L.J.; Zhou, H.; Zhang, H.M.; Wei, X.H.; Liu, G.; Liu, X.G. Oral application of Magnesium-L-Threonate attenuates vincristine-induced allodynia and hyperalgesia by normalization of tumor necrosis factor-α/Nuclear Factor-κB signaling. Anesthesiology, 2017, 126(6), 1151-1168.
[http://dx.doi.org/10.1097/ALN.0000000000001601] [PMID: 28306698]
[45]
Jeon, K.I.; Xu, X.; Aizawa, T.; Lim, J.H.; Jono, H.; Kwon, D.S.; Abe, J.; Berk, B.C.; Li, J.D.; Yan, C. Vinpocetine inhibits NF-kappaB-dependent inflammation via an IKK-dependent but PDE-independent mechanism. Proc. Natl. Acad. Sci. USA, 2010, 107(21), 9795-9800.
[http://dx.doi.org/10.1073/pnas.0914414107] [PMID: 20448200]
[46]
Takada, Y.; Kobayashi, Y.; Aggarwal, B.B. Evodiamine abolishes constitutive and inducible NF-kappaB activation by inhibiting IkappaBalpha kinase activation, thereby suppressing NF-kappaB-regulated antiapoptotic and metastatic gene expression, up-regulating apoptosis, and inhibiting invasion. J. Biol. Chem., 2005, 280(17), 17203-17212.
[http://dx.doi.org/10.1074/jbc.M500077200] [PMID: 15710601]
[47]
Kuo, H.P.; Chuang, T.C.; Tsai, S.C.; Tseng, H.H.; Hsu, S.C.; Chen, Y.C.; Kuo, C.L.; Kuo, Y.H.; Liu, J.Y.; Kao, M.C. Berberine, an isoquinoline alkaloid, inhibits the metastatic potential of breast cancer cells via Akt pathway modulation. J. Agric. Food Chem., 2012, 60(38), 9649-9658.
[http://dx.doi.org/10.1021/jf302832n] [PMID: 22950834]
[48]
Pandey, M.K.; Sung, B.; Kunnumakkara, A.B.; Sethi, G.; Chaturvedi, M.M.; Aggarwal, B.B. Berberine modifies cysteine 179 of IkappaBalpha kinase, suppresses nuclear factor-kappaB-regulated antiapoptotic gene products, and potentiates apoptosis. Cancer Res., 2008, 68(13), 5370-5379.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-0511] [PMID: 18593939]
[49]
Zhu, L.; Liu, J.; Ma, S.; Zhang, S.; Long Noncoding, R.N.A. MALAT-1 Can Predict Metastasis and a Poor Prognosis: A Meta-Analysis, Pathology oncology research. POR, 2015, 21, 1259-1264.
[PMID: 26159858]
[50]
Liang, Y.; Xu, R.Z.; Zhang, L.; Zhao, X.Y. Berbamine, a novel nuclear factor kappaB inhibitor, inhibits growth and induces apoptosis in human myeloma cells. Acta Pharmacol. Sin., 2009, 30(12), 1659-1665.
[http://dx.doi.org/10.1038/aps.2009.167] [PMID: 19960011]
[51]
Shu, G.; Yue, L.; Zhao, W.; Xu, C.; Yang, J.; Wang, S.; Yang, X. Isoliensinine, a bioactive alkaloid derived from embryos of nelumbo nucifera induces hepatocellular carcinoma cell apoptosis through suppression of NF-Kb signaling. J. Agric. Food Chem., 2015, 63, 8793-8803.
[52]
Du, H.P.; Shen, J.K.; Yang, M.; Wang, Y.Q.; Yuan, X.Q.; Ma, Q.L.; Jin, J. 4-Chlorobenzoyl berbamine induces apoptosis and G2/M cell cycle arrest through the PI3K/Akt and NF-kappaB signal pathway in lymphoma cells. Oncol. Rep., 2010, 23(3), 709-716.
[PMID: 20127010]
[53]
Lin, X.; Li, Q.; Wang, Y.J.; Ju, Y.W.; Chi, Z.Q.; Wang, M.W.; Liu, J.G. Morphine inhibits doxorubicin-induced reactive oxygen species generation and nuclear factor kappaB transcriptional activation in neuroblastoma SH-SY5Y cells. Biochem. J., 2007, 406(2), 215-221.
[http://dx.doi.org/10.1042/BJ20070186] [PMID: 17542780]
[54]
Yang, Z.; Li, C.; Wang, X.; Zhai, C.; Yi, Z.; Wang, L.; Liu, B.; Du, B.; Wu, H.; Guo, X.; Liu, M.; Li, D.; Luo, J. Dauricine induces apoptosis, inhibits proliferation and invasion through inhibiting NF-kappaB signaling pathway in colon cancer cells. J. Cell. Physiol., 2010, 225(1), 266-275.
[http://dx.doi.org/10.1002/jcp.22261] [PMID: 20509140]
[55]
Bottero, V.; Busuttil, V.; Loubat, A.; Magné, N.; Fischel, J.L.; Milano, G.; Peyron, J.F. Activation of nuclear factor kappaB through the IKK complex by the topoisomerase poisons SN38 and doxorubicin: A brake to apoptosis in HeLa human carcinoma cells. Cancer Res., 2001, 61(21), 7785-7791.
[PMID: 11691793]
[56]
Cusack, J.C., Jr; Liu, R.; Baldwin, A.S. Jr Inducible chemoresistance to 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothe cin (CPT-11) in colorectal cancer cells and a xenograft model is overcome by inhibition of nuclear factor-kappaB activation. Cancer Res., 2000, 60(9), 2323-2330.
[PMID: 10811101]
[57]
Chaturvedi, M.M.; Kumar, A.; Darnay, B.G.; Chainy, G.B.; Agarwal, S.; Aggarwal, B.B. Sanguinarine (pseudochelerythrine) is a potent inhibitor of NF-kappaB activation, IkappaBalpha phosphorylation, and degradation. J. Biol. Chem., 1997, 272(48), 30129-30134.
[http://dx.doi.org/10.1074/jbc.272.48.30129] [PMID: 9374492]
[58]
Jin, H.R.; Jin, S.Z.; Cai, X.F.; Li, D.; Wu, X.; Nan, J.X.; Lee, J.J.; Jin, X. Cryptopleurine targets NF-κB pathway, leading to inhibition of gene products associated with cell survival, proliferation, invasion, and angiogenesis. PLoS One, 2012, 7(6), e40355.
[http://dx.doi.org/10.1371/journal.pone.0040355] [PMID: 22768286]
[59]
Chiu, F.L.; Lin, J.K. Tomatidine inhibits iNOS and COX-2 through suppression of NF-kappaB and JNK pathways in LPS-stimulated mouse macrophages. FEBS Lett., 2008, 582(16), 2407-2412.
[http://dx.doi.org/10.1016/j.febslet.2008.05.049] [PMID: 18544347]
[60]
Ghezali, L.; Leger, D.Y.; Limami, Y.; Cook-Moreau, J.; Beneytout, J.L.; Liagre, B. Cyclopamine and jervine induce COX-2 overexpression in human erythroleukemia cells but only cyclopamine has a pro-apoptotic effect. Exp. Cell Res., 2013, 319(7), 1043-1053.
[http://dx.doi.org/10.1016/j.yexcr.2013.01.014] [PMID: 23357584]
[61]
Martínez-García, E.; Irigoyen, M.; Ansó, E.; Martínez-Irujo, J.J.; Rouzaut, A. Recurrent exposure to nicotine differentiates human bronchial epithelial cells via epidermal growth factor receptor activation. Toxicol. Appl. Pharmacol., 2008, 228(3), 334-342.
[http://dx.doi.org/10.1016/j.taap.2007.12.016] [PMID: 18262213]
[62]
Micheau, O.; Dufour, F.; Walczak, H. Thiocolchicoside a semi-synthetic derivative of the Glory Lily: A new weapon to fight metastatic bone resorption? Br. J. Pharmacol., 2012, 165(7), 2124-2126.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01792.x] [PMID: 22122264]
[63]
Reuter, S.; Prasad, S.; Phromnoi, K.; Ravindran, J.; Sung, B.; Yadav, V.R.; Kannappan, R.; Chaturvedi, M.M.; Aggarwal, B.B. Thiocolchicoside exhibits anticancer effects through downregulation of NF-κB pathway and its regulated gene products linked to inflammation and cancer. Cancer Prev. Res. (Phila.), 2010, 3(11), 1462-1472.
[http://dx.doi.org/10.1158/1940-6207.CAPR-10-0037] [PMID: 20978115]
[64]
Wong, C.P.; Seki, A.; Horiguchi, K.; Shoji, T.; Arai, T.; Nugroho, A.E.; Hirasawa, Y.; Sato, F.; Kaneda, T.; Morita, H.; Bisleuconothine, A. Bisleuconothine A induces autophagosome formation by interfering with AKT-mTOR signaling pathway. J. Nat. Prod., 2015, 78(7), 1656-1662.
[http://dx.doi.org/10.1021/acs.jnatprod.5b00258] [PMID: 26176165]
[65]
Wan, X.; Yokoyama, Y.; Shinohara, A.; Takahashi, Y.; Tamaya, T. PTEN augments staurosporine-induced apoptosis in PTEN-null Ishikawa cells by downregulating PI3K/Akt signaling pathway. Cell Death Differentiate., 2002, 9, 414-420.
[66]
Kumar, S.; Guru, S.K.; Pathania, A.S.; Manda, S.; Kumar, A.; Bharate, S.B.; Vishwakarma, R.A.; Malik, F.; Bhushan, S. Fascaplysin induces caspase mediated crosstalk between apoptosis and autophagy through the inhibition of PI3K/AKT/mTOR signaling cascade in human leukemia HL-60 cells. J. Cell. Biochem., 2015, 116(6), 985-997.
[http://dx.doi.org/10.1002/jcb.25053] [PMID: 25561006]
[67]
Grotegut, S.; Kappler, R.; Tarimoradi, S.; Lehembre, F.; Christofori, G.; Von Schweinitz, D. Hepatocyte growth factor protects hepatoblastoma cells from chemotherapy-induced apoptosis by AKT activation. Int. J. Oncol., 2010, 36(5), 1261-1267.
[PMID: 20372801]
[68]
Mei, Y.; Xie, C.; Xie, W.; Tian, X.; Li, M.; Wu, M. Noxa/Mcl-1 balance regulates susceptibility of cells to camptothecin-induced apoptosis. Neoplasia, 2007, 9(10), 871-881.
[http://dx.doi.org/10.1593/neo.07589] [PMID: 17971907]
[69]
C. PS. W. CH, J. YF, W.C.J.J.o. agricultural, f. chemistry, Alphachaconine-reduced metastasis involves a PI3K/Akt signaling pathway with downregulation of NF-kappaB in human lung adenocarcinoma A549 cells 2007, 55, 11035-11043.
[70]
Chen, Y.; Tang, Q.; Wu, J.; Zheng, F.; Yang, L.; Hann, S.S. Inactivation of PI3-K/Akt and reduction of SP1 and p65 expression increase the effect of solamargine on suppressing EP4 expression in human lung cancer cells. J. Exp. Clin. Cancer Res., 2015, 34, 154.
[http://dx.doi.org/10.1186/s13046-015-0272-0] [PMID: 26689593]
[71]
Huang, C.Z.; Wang, Y.F.; Zhang, Y.; Peng, Y.M.; Liu, Y.X.; Ma, F.; Jiang, J.H.; Wang, Q.D. Cepharanthine hydrochloride reverses P glycoprotein-mediated multidrug resistance in human ovarian carcinoma A2780/Taxol cells by inhibiting the PI3K/Akt signaling pathway. Oncol. Rep., 2017, 38(4), 2558-2564.
[http://dx.doi.org/10.3892/or.2017.5879] [PMID: 28791369]
[72]
Ma, J.; Wang, L.; Li, J.; Zhang, G.; Tao, H.; Li, X.; Sun, D.; Hu, Y. Swainsonine inhibits invasion and the EMT process in esophageal carcinoma cells by targeting twist1. Oncol. Res., 2018, 26(8), 1207-1213.
[http://dx.doi.org/10.3727/096504017X15046134836575] [PMID: 28899457]
[73]
Tian, F.; Ding, D.; Li, D. Fangchinoline targets PI3K and suppresses PI3K/AKT signaling pathway in SGC7901 cells. Int. J. Oncol., 2015, 46(6), 2355-2363.
[http://dx.doi.org/10.3892/ijo.2015.2959] [PMID: 25872479]
[74]
Zhou, B.G.; Wei, C.S.; Zhang, S.; Zhang, Z.; Gao, H.M. Matrine reversed multidrug resistance of breast cancer MCF-7/ADR cells through PI3K/AKT signaling pathway. J. Cell. Biochem., 2018, 119(5), 3885-3891.
[http://dx.doi.org/10.1002/jcb.26502] [PMID: 29130495]
[75]
Kuo, H.P.; Chuang, T.C.; Yeh, M.H.; Hsu, S.C.; Way, T.D.; Chen, P.Y.; Wang, S.S.; Chang, Y.H.; Kao, M.C.; Liu, J.Y. Growth suppression of HER2-overexpressing breast cancer cells by berberine via modulation of the HER2/PI3K/Akt signaling pathway. J. Agric. Food Chem., 2011, 59(15), 8216-8224.
[http://dx.doi.org/10.1021/jf2012584] [PMID: 21699261]
[76]
Han, B.; Jiang, P.; Li, Z.; Yu, Y.; Huang, T.; Ye, X.; Li, X. Coptisine-induced apoptosis in human colon cancer cells (HCT-116) is mediated by PI3K/Akt and mitochondrial-associated apoptotic pathway. Phytomedicine, 2018, 48, 152-160.
[http://dx.doi.org/10.1016/j.phymed.2017.12.027] [PMID: 30195873]
[77]
Chen, S.; Jin, Z.; Dai, L.; Wu, H.; Wang, J.; Wang, L.; Zhou, Z.; Yang, L.; Gao, W. Aloperine induces apoptosis and inhibits invasion in MG-63 and U2OS human osteosarcoma cells. Biomed. Pharmacother., 2018, 97, 45-52.
[78]
Li, L.; Wang, X.; Sharvan, R.; Gao, J.; Qu, S. Berberine could inhibit thyroid carcinoma cells by inducing mitochondrial apoptosis, G0/G1 cell cycle arrest and suppressing migration via PI3K-AKT and MAPK signaling pathways. Biomed. Pharmacother., 2017, 95, 1225-1231.
[79]
Hassanein, E.H.M.; Shalkami, A.S.; Khalaf, M.M.; Mohamed, W.R.; Hemeida, R.A.M. The impact of Keap1/Nrf2, P38MAPK/NF-kappaB and Bax/Bcl2/caspase-3 signaling pathways in the protective effects of berberine against methotrexate-induced nephrotoxicity. Biomed. Pharmacother., 2019, 109, 47-56.
[80]
Hu, S.; Chen, C.W.; Chen, S.T.; Tsui, K.H.; Tang, T.K.; Cheng, H.T.; Hwang, G.S.; Yu, J.W.; Li, Y.C.; Wang, P.S.; Wang, S.W. Inhibitory effect of berberine on interleukin-2 secretion from PHA-treated lymphocytic Jurkat cells. Int. Immunopharmacol., 2019, 66, 267-273.
[http://dx.doi.org/10.1016/j.intimp.2018.11.020] [PMID: 30502647]
[81]
Kim, J.S.; Oh, D.; Yim, M.J.; Park, J.J.; Kang, K.R.; Cho, I.A.; Moon, S.M.; Oh, J.S.; You, J.S.; Kim, C.S.; Kim, D.K.; Lee, S.Y.; Lee, G.J. Im, H.J.; Kim, S.G. Berberine induces FasL-related apoptosis through p38 activation in KB human oral cancer cells. Oncol. Rep., 2015, 33(4), 1775-1782.
[http://dx.doi.org/10.3892/or.2015.3768] [PMID: 25634589]
[82]
Zheng, F.; Tang, Q.; Wu, J.; Zhao, S.; Liang, Z.; Li, L.; Wu, W.; Hann, S. p38α MAPK-mediated induction and interaction of FOXO3a and p53 contribute to the inhibited-growth and induced-apoptosis of human lung adenocarcinoma cells by berberine. J. Exp. Clin. Cancer Res., 2014, 33, 36.
[http://dx.doi.org/10.1186/1756-9966-33-36] [PMID: 24766860]
[83]
Lin, Z.; Li, S.; Guo, P.; Wang, L.; Zheng, L.; Yan, Z.; Chen, X.; Cheng, Z.; Yan, H.; Zheng, C.; Zhao, C. Columbamine suppresses hepatocellular carcinoma cells through down-regulation of PI3K/AKT, p38 and ERK1/2 MAPK signaling pathways. Life Sci., 2019, 218, 197-204.
[http://dx.doi.org/10.1016/j.lfs.2018.12.038] [PMID: 30582951]
[84]
Xu, W.; Wang, X.; Tu, Y.; Masaki, H.; Tanaka, S.; Onda, K.; Sugiyama, K.; Yamada, H.; Hirano, T. Tetrandrine and cepharanthine induce apoptosis through caspase cascade regulation, cell cycle arrest, MAPK activation and PI3K/Akt/mTOR signal modification in glucocorticoid resistant human leukemia Jurkat T cells. Chem. Biol. Interact., 2019, 310, 108726.
[http://dx.doi.org/10.1016/j.cbi.2019.108726] [PMID: 31255635]
[85]
Wu, J.M.; Chen, Y.; Chen, J.C.; Lin, T.Y.; Tseng, S.H. Tetrandrine induces apoptosis and growth suppression of colon cancer cells in mice. Cancer Lett., 2010, 287(2), 187-195.
[http://dx.doi.org/10.1016/j.canlet.2009.06.009] [PMID: 19586712]
[86]
Zhang, X.; Wang, X.; Wu, T.; Li, B.; Liu, T.; Wang, R.; Liu, Q.; Liu, Z.; Gong, Y.; Shao, C. Isoliensinine induces apoptosis in triple-negative human breast cancer cells through ROS generation and p38 MAPK/JNK activation. Sci. Rep., 2015, 5, 12579.
[http://dx.doi.org/10.1038/srep12579] [PMID: 26219228]
[87]
Li, H.; Sun, L.; Li, H.; Lv, X.; Semukunzi, H.; Li, R.; Yu, J.; Yuan, S.; Lin, S. Lin, DT-13, a saponin monomer 13 of the Dwarf lilyturf tuber, synergized with vinorelbine to induce mitotic arrest via activation of ERK signaling pathway in NCI-H1299 cells. Biomed. Pharmacother., 2017, 89, 1277-1285.
[88]
Fu, R.; Wang, X.; Hu, Y.; Du, H.; Dong, B.; Ao, S.; Zhang, L.; Sun, Z.; Zhang, L.; Lv, G.; Ji, J. Solamargine inhibits gastric cancer progression by regulating the expression of lncNEAT1_2 via the MAPK signaling pathway. Int. J. Oncol., 2019, 54(5), 1545-1554.
[http://dx.doi.org/10.3892/ijo.2019.4744] [PMID: 30864686]
[89]
Shi, D.; Guo, W.; Chen, W.; Fu, L.; Wang, J.; Tian, Y.; Xiao, X.; Kang, T.; Huang, W.; Deng, W. Nicotine promotes proliferation of human nasopharyngeal carcinoma cells by regulating α7AChR, ERK, HIF-1α and VEGF/PEDF signaling. PLoS One, 2012, 7(8), e43898.
[http://dx.doi.org/10.1371/journal.pone.0043898] [PMID: 22952803]
[90]
Xiang, T.; Fei, R.; Wang, Z.; Shen, Z.; Qian, J.; Chen, W. Nicotine enhances invasion and metastasis of human colorectal cancer cells through the nicotinic acetylcholine receptor downstream p38 MAPK signaling pathway. Oncol. Rep., 2016, 35(1), 205-210.
[http://dx.doi.org/10.3892/or.2015.4363] [PMID: 26530054]
[91]
Jin, T.; Hao, J.; Fan, D. Nicotine induces aberrant hypermethylation of tumor suppressor genes in pancreatic epithelial ductal cells. Biochem. Biophys. Res. Commun., 2018, 499(4), 934-940.
[http://dx.doi.org/10.1016/j.bbrc.2018.04.022] [PMID: 29626481]
[92]
Kwon, Y.; Song, J.; Lee, H.; Kim, E.Y.; Lee, K.; Lee, S.K.; Kim, S. Design, Synthesis, and biological activity of sulfonamide analogues of antofine and cryptopleurine as potent and orally active antitumor agents. J. Med. Chem., 2015, 58(19), 7749-7762.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00764] [PMID: 26393416]
[93]
Shi, X.; Zhu, M.; Gong, Z.; Yang, T.; Yu, R.; Wang, J.; Zhang, Y. Homoharringtonine suppresses LoVo cell growth by inhibiting EphB4 and the PI3K/AKT and MAPK/EKR1/2 signaling pathways. Food Chem. Toxicol., 2020, 136, 110960.
[http://dx.doi.org/10.1016/j.fct.2019.110960] [PMID: 31726078]
[94]
Fan, Y.; Jiang, Y.; Liu, J.; Kang, Y.; Li, R.; Wang, J. The anti-tumor activity and mechanism of alkaloids from Aconitum szechenyianum Gay. Bioorg. Med. Chem. Lett., 2016, 26(2), 380-387.
[http://dx.doi.org/10.1016/j.bmcl.2015.12.006] [PMID: 26711147]
[95]
Dai, F.; Chen, Y.; Song, Y.; Huang, L.; Zhai, D.; Dong, Y.; Lai, L.; Zhang, T.; Li, D.; Pang, X.; Liu, M.; Yi, Z. A natural small molecule harmine inhibits angiogenesis and suppresses tumour growth through activation of p53 in endothelial cells. PLoS One, 2012, 7(12), e52162.
[http://dx.doi.org/10.1371/journal.pone.0052162] [PMID: 23300602]
[96]
Zhang, M.; Xue, E.; Shao, W. Andrographolide promotes vincristine-induced SK-NEP-1 tumor cell death via PI3K-AKT-p53 signaling pathway. Drug Des. Devel. Ther., 2016, 10, 3143-3152.
[http://dx.doi.org/10.2147/DDDT.S113838] [PMID: 27729773]
[97]
Luo, X.; Gu, J.; Zhu, R.; Feng, M.; Zhu, X.; Li, Y.; Fei, J. Integrative analysis of differential miRNA and functional study of miR-21 by seed-targeting inhibition in multiple myeloma cells in response to berberine. BMC Syst. Biol., 2014, 8, 82.
[http://dx.doi.org/10.1186/1752-0509-8-82] [PMID: 25000828]
[98]
Dudgeon, D.D.; Shinde, S.N.; Shun, T.Y.; Lazo, J.S.; Strock, C.J.; Giuliano, K.A.; Taylor, D.L.; Johnston, P.A.; Johnston, P.A. Characterization and optimization of a novel protein-protein interaction biosensor high-content screening assay to identify disruptors of the interactions between p53 and hDM2. Assay Drug Dev. Technol., 2010, 8(4), 437-458.
[http://dx.doi.org/10.1089/adt.2010.0281] [PMID: 20662736]
[99]
Huang, S.; Zhao, S.M.; Shan, L.H.; Zhou, X.L. Antitumor activity of nervosine VII, and the crosstalk between apoptosis and autophagy in HCT116 human colorectal cancer cells. Chin. J. Nat. Med., 2020, 18(2), 81-89.
[http://dx.doi.org/10.1016/S1875-5364(20)30009-1] [PMID: 32172951]

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