Preparation of Lycium barbarum Active Glycopeptide and Investigation of Its
Apoptotic Effects on Melanoma

Jinghua      Qi; Xingli      Qi; Hongyuan      Chen; Wen      Rui
doi:10.2174/0118715206274639231103050807
Abstract

Introduction: The increasing number of studies have shown that Lycium barbarum polysaccharides possess anti-tumor effects. However, the determination of the active ingredients and their mechanism against melanoma inhibition are still unknown.
Methods: In this study, we aimed to investigate the mechanisms of action of Lycium barbarum active glycopeptide (LBAG) on melanoma. LBAG was extracted and isolated from the fruit of Lycium barbarum using aqueous alcoholic precipitation and identified using ultra-performance liquid chromatography-quadrupole-time of flightmass spectrometry. Various assays including cell apoptosis, cell cycle analysis, colony formation assay, cell scratch test, flow cytometry, and Western blot were performed to evaluate the effects of LBAG on melanoma.
Results: The results showed that LBAG has a molecular weight of 10-15 kDa and contains Man, Rha, GlcA, Glc, Gal, and Ara18 amino acids. Treatment with LBAG significantly decreased B16 cell proliferation and induced cell cycle arrest at the G0/G phase, accompanied by the accumulation of reactive oxygen species. Western blot analysis revealed that the phosphorylation of P38-MAPK and AKT, as well as the expression of N-acetyl-Lcysteine, were related to cell apoptosis and cell cycle regulation. In mouse xenografts, LBAG inhibited tumor growth through the P38-MAPK and AKT signaling pathways.
Conclusion: In conclusion, the anti-melanoma activity of LBAG may induce apoptosis in cancer cells through ROSmediated activation of the P38-MAPK and AKT signaling pathways. These findings provide a foundation for further research on the anti-melanoma potential of LBAG.
« Previous Next »
Graphical Abstract

[1]
Neelam, K.; Dey, S.; Sim, R.; Lee, J.; Au Eong, K.G. Fructus lycii: a natural dietary supplement for amelioration of retinal diseases. Nutrients,  2021, 13(1), 246.
 [http://dx.doi.org/10.3390/nu13010246] [PMID: 33467087]

[2]
Liu, H.; Zhu, L.; Chen, L.; Li, L. Therapeutic potential of traditional Chinese medicine in atherosclerosis: A review. Phytother. Res.,  2022, 36(11), 4080-4100.
 [http://dx.doi.org/10.1002/ptr.7590] [PMID: 36029188]

[3]
Liu, C.; Madeira, L.A.; Sartori, J.R.; Pezzato, A.C.; Gonçalves, J.; Cruz, V.; Kuibida, K.V.; Pinheiro, D.F. Food and Chemical Toxicology, 2007 ‘DNA solutionR in cigarette filters reduces polycyclic aromatic hydrocarbon (PAH) levels in mainstream tobacco smoke’ M. Lodovici, V. Akpan, S. Caldini, B. Akanju, and P. Dolara. Food Chem. Toxicol.,  2008, 46(12), 3851-3852.
 [http://dx.doi.org/10.1016/j.fct.2008.09.011] [PMID: 18835416]

[4]
Letizia, C.S.; Cocchiara, J.; Wellington, G.A.; Funk, C.; Api, A.M. Food and chemical toxicology. Food Chem. Toxicol.,  2000, 38(Suppl. 3), S1-S236.
 [PMID: 11056264]

[5]
Wu, D.T.; Guo, H.; Shang, L.; Shing-Chung, L.; Li, Z.; Lin, D.R.; Wen, Q. Review of the structural characterization, quality evaluation, and industrial application of Lycium barbarum polysaccharides. Trends Food Sci. Technol.,  2018, 79, S0924224417306295.

[6]
Meng, J.; Liu, Z.; Gou, C.L.; Rogers, K.M.; Yu, W.J.; Zhang, S.S.; Yuan, Y.W.; Zhang, L. Geographical origin of Chinese wolfberry (goji) determined by carbon isotope analysis of specific volatile compounds. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.,  2019, 1105, 104-112.
 [http://dx.doi.org/10.1016/j.jchromb.2018.12.011] [PMID: 30580182]

[7]
Qi, Y.; Duan, G.; Fan, G.; Peng, N. Effect of Lycium barbarum polysaccharides on cell signal transduction pathways. Biomed. Pharmacother.,  2022, 147, 112620.
 [http://dx.doi.org/10.1016/j.biopha.2022.112620] [PMID: 35032768]

[8]
Yao, R.; Heinrich, M.; Weckerle, C.S. The genus Lycium as food and medicine: A botanical, ethnobotanical and historical review. J. Ethnopharmacol.,  2018, 212, 50-66.
 [http://dx.doi.org/10.1016/j.jep.2017.10.010] [PMID: 29042287]

[9]
Liu, Z.C.; Yu, W.W.; Zhou, H.C.; Lan, Z.C.; Wu, T.; Xiong, S.M.; Yan, L.; Liu, H.B. Lycium barbarum polysaccharides ameliorate LPS-induced inflammation of RAW264.7 cells and modify the behavioral score of peritonitis mice. J. Food Biochem.,  2021, 45(10), e13889.
 [http://dx.doi.org/10.1111/jfbc.13889] [PMID: 34426988]

[10]
Lei, X.; Huo, P.; Wang, Y.; Xie, Y.; Shi, Q.; Tu, H.; Yao, J.; Mo, Z.; Zhang, S. Lycium barbarum polysaccharides improve testicular spermatogenic function in streptozotocin-induced diabetic rats. Front. Endocrinol.,  2020, 11, 164.
 [http://dx.doi.org/10.3389/fendo.2020.00164] [PMID: 32362869]

[11]
Duan, X.; Lan, Y.; Zhang, X.; Hou, S.; Chen, J.; Ma, B.; Xia, Y.; Su, C. Lycium barbarum Polysaccharides promote maturity of murine dendritic cells through toll-like receptor 4-Erk1/2-Blimp1 signaling pathway. J. Immunol. Res.,  2020, 2020, 1-15.
 [http://dx.doi.org/10.1155/2020/1751793] [PMID: 33344654]

[12]
Feng, L.; Xiao, X.; Liu, J.; Wang, J.; Zhang, N.; Bing, T.; Liu, X.; Zhang, Z.; Shangguan, D. Immunomodulatory effects of Lycium barbarum polysaccharide extract and its uptake behaviors at the cellular level. Molecules,  2020, 25(6), 1351.
 [http://dx.doi.org/10.3390/molecules25061351] [PMID: 32188121]

[13]
Wang, Y.; Xiao, J.; Duan, Y.; Miao, M.; Huang, B.; Chen, J.; Cheng, G.; Zhou, X.; Jin, Y.; He, J.; Li, Z.; So, K.F. Lycium barbarum Polysaccharide Ameliorates Sjögren’s Syndrome in a Murine Model. Mol. Nutr. Food Res.,  2021, 65(11), 2001118.
 [http://dx.doi.org/10.1002/mnfr.202001118] [PMID: 33825332]

[14]
Song, Q.; Yong, H.M.; Yang, L.V.L.; Liang, Y.Q.; Liu, Z.X.; Niu, D.S.; Bai, Z.G. Lycium barbarum polysaccharide protects against osteonecrosis of femoral head via regulating Runx2 expression. Injury,  2022, 53(4), 1361-1367.
 [http://dx.doi.org/10.1016/j.injury.2021.12.056] [PMID: 35082056]

[15]
Liang, R.; Zhao, Q.; Zhu, Q.; He, X.; Gao, M.; Wang, Y. Lycium barbarum polysaccharide protects ARPE 19 cells against H2O 2 induced oxidative stress via the Nrf2/HO 1 pathway. Mol. Med. Rep.,  2021, 24(5), 769.
 [http://dx.doi.org/10.3892/mmr.2021.12409] [PMID: 34490478]

[16]
Liu, J.J.; Zhao, G.X.; He, L.L.; Wang, Z.; Zibrila, A.I.; Niu, B.C.; Gong, H.Y.; Xu, J.N.; Soong, L.; Li, C.F.; Lu, Y. Lycium barbarum polysaccharides inhibit ischemia/reperfusion-induced myocardial injury via the Nrf2 antioxidant pathway. Toxicol. Rep.,  2021, 8, 657-667.
 [http://dx.doi.org/10.1016/j.toxrep.2021.03.019] [PMID: 33868952]

[17]
Wu, Q.; Liu, L.; Wang, X.; Lang, Z.; Meng, X.; Guo, S.; Yan, B.; Zhan, T.; Zheng, H.; Wang, H. Lycium barbarum polysaccharides attenuate kidney injury in septic rats by regulating Keap1-Nrf2/ARE pathway. Life Sci.,  2020, 242, 117240.
 [http://dx.doi.org/10.1016/j.lfs.2019.117240] [PMID: 31891722]

[18]
Zhou, H.; Ding, S.; Sun, C.; Fu, J.; Yang, D.; Wang, X.; Wang, C.; Wang, L. Lycium barbarum extracts extend lifespan and alleviate proteotoxicity in Caenorhabditis elegans. Front. Nutr.,  2022, 8, 815947.
 [http://dx.doi.org/10.3389/fnut.2021.815947] [PMID: 35096951]

[19]
Inulin and Lycium barbarum polysaccharides ameliorate diabetes by enhancing gut barrier via modulating gut microbiota and activating gut mucosal TLR2 + intraepithelial γδ T cells in rats. J. Funct. Foods,  2022, 79, 104407.

[20]
Wan, F.; Ma, F.; Wu, J.; Qiao, X.; Chen, M.; Li, W.; Ma, L. Effect of Lycium barbarum Polysaccharide on decreasing serum amyloid A3 expression through inhibiting NF-κB activation in a mouse model of diabetic nephropathy. Anal. Cell. Pathol.,  2022, 2022, 1-12.
 [http://dx.doi.org/10.1155/2022/7847135] [PMID: 35132370]

[21]
Yao, Q.; Zhou, Y.; Yang, Y.; Cai, L.; Xu, L.; Han, X.; Guo, Y.; Li, P.A. Activation of Sirtuin1 by Lyceum barbarum polysaccharides in protection against diabetic cataract. J. Ethnopharmacol.,  2020, 261, 113165.
 [http://dx.doi.org/10.1016/j.jep.2020.113165] [PMID: 32730875]

[22]
Gao, L.L.; Li, Y.X.; Ma, J.M.; Guo, Y.Q.; Li, L.; Gao, Q.H.; Fan, Y.N.; Zhang, M.W.; Tao, X.J.; Yu, J.Q.; Yang, J.J. Correction to: Effect of Lycium barbarum polysaccharide supplementation in non-alcoholic fatty liver disease patients: Study protocol for a randomized controlled trial. Trials,  2021, 22(1), 672.
 [http://dx.doi.org/10.1186/s13063-021-05649-z] [PMID: 34593033]

[23]
Zhang, M.; Li, F.; Pokharel, S.; Ma, T.; Wang, X.; Wang, Y.; Wang, W.; Lin, R. Lycium barbarum polysaccharide protects against Homocysteine-induced Vascular smooth muscle cell proliferation and phenotypic transformation via PI3K/Akt pathway. J. Mol. Histol.,  2020, 51(6), 629-637.
 [http://dx.doi.org/10.1007/s10735-020-09909-1] [PMID: 32897463]

[24]
Liu, H.; Zhou, X.; Huang, S.; Yang, J.; Liu, R.; Liu, C. Lycium barbarum polysaccharides and wolfberry juice prevent DEHP-induced hepatotoxicity via PXR-regulated detoxification pathway. Molecules,  2021, 26(4), 859.
 [http://dx.doi.org/10.3390/molecules26040859] [PMID: 33562043]

[25]
Wang, H.; Li, Y.; Liu, J.; Di, D.; Liu, Y.; Wei, J. Hepatoprotective effect of crude polysaccharide isolated from Lycium barbarum L. against alcohol-induced oxidative damage involves Nrf2 signaling. Food Sci. Nutr.,  2020, 8(12), 6528-6538.
 [http://dx.doi.org/10.1002/fsn3.1942] [PMID: 33312537]

[26]
Fanzhen, M. Function of Lycium barbarum polysaccharide on proliferation and apoptosis of human lung cancer A549 cells. World Sci-Tech R$D, 2012.

[27]
Kwok, S.S.; Bu, Y.; Lo, A.C.Y.; Chan, T.C.Y.; So, K.F.; Lai, J.S.M.; Shih, K.C. A systematic review of potential therapeutic use of Lycium barbarum polysaccharides in disease. BioMed Res. Int.,  2019, 2019, 1-18.
 [http://dx.doi.org/10.1155/2019/4615745] [PMID: 30891458]

[28]
Zhou, J.; Li, H.; Wang, F.; Wang, H.; Chai, R.; Li, J.; Jia, L.; Wang, K.; Zhang, P.; Zhu, L.; Yang, H. Effects of 2,4-dichlorophenoxyacetic acid on the expression of NLRP3 inflammasome and autophagy-related proteins as well as the protective effect of Lycium barbarum polysaccharide in neonatal rats. Environ. Toxicol.,  2021, 36(12), 2454-2466.
 [http://dx.doi.org/10.1002/tox.23358] [PMID: 34464015]

[29]
Lakshmanan, Y.; Wong, F.S.Y.; Zuo, B.; So, K.F.; Bui, B.V.; Chan, H.H.L. Posttreatment intervention with Lycium Barbarum polysaccharides is neuroprotective in a rat model of chronic ocular hypertension. Invest. Ophthalmol. Vis. Sci.,  2019, 60(14), 4606-4618.
 [http://dx.doi.org/10.1167/iovs.19-27886] [PMID: 31756254]

[30]
Tian, X.; Liang, T.; Liu, Y.; Ding, G.; Zhang, F.; Ma, Z. Extraction, structural characterization, and biological functions of Lycium Barbarum Polysaccharides: A review. Biomolecules,  2019, 9(9), 389.
 [http://dx.doi.org/10.3390/biom9090389] [PMID: 31438522]

[31]
Peng, X.; Tian, G. Structural characterization of the glycan part of glycoconjugate LbGp2 from Lycium barbarum L. Carbohydr. Res.,  2001, 331(1), 95-99.
 [http://dx.doi.org/10.1016/S0008-6215(00)00321-9] [PMID: 11284511]

[32]
Huang, L.J.; Tian, G.Y.; Ji, G.Z. Structure elucidation of glycan of glycoconjugate LbGp3 isolated from the fruit of Lycium barbarum L. J. Asian Nat. Prod. Res.,  1999, 1(4), 259-267.
 [http://dx.doi.org/10.1080/10286029908039874] [PMID: 11523546]

[33]
Peng, X.M.; Huang, L.J.; Qi, C.H.; Zhang, Y.X.; Tian, G.Y. Studies on chemistry and immuno- modulating mechanism of a glycoconjugate from Lycium barbarum L. Chin. J. Chem.,  2001, 19(12), 1190-1197.
 [http://dx.doi.org/10.1002/cjoc.20010191206]

[34]
Zhou, X.; Zhang, Z.; Shi, H.; Liu, Q.; Chang, Y.; Feng, W.; Zhu, S.; Sun, S. Effects of Lycium barbarum glycopeptide on renal and testicular injury induced by di(2-ethylhexyl) phthalate. Cell Stress Chaperones,  2022, 27(3), 257-271.
 [http://dx.doi.org/10.1007/s12192-022-01266-0] [PMID: 35362893]

[35]
Huang, Y.; Zheng, Y.; Yang, F.; Feng, Y.; Xu, K.; Wu, J.; Qu, S.; Yu, Z.; Fan, F.; Huang, L.; Qin, M.; He, Z.; Nie, K.; So, K.F. Lycium barbarum Glycopeptide prevents the development and progression of acute colitis by regulating the composition and diversity of the gut microbiota in mice. Front. Cell. Infect. Microbiol.,  2022, 12, 921075.
 [http://dx.doi.org/10.3389/fcimb.2022.921075] [PMID: 36017369]

[36]
Guang, D.; Lu, L.; Jianguo, F. Experimental study on the enhancement of murine splenic lymphocyte proliferation by Lycium barbarum glycopeptide. J. Huazhong Univ. Sci. Technolog. Med. Sci.,  2004, 24(5), 518-520, 527.
 [http://dx.doi.org/10.1007/BF02831125] [PMID: 15641709]

[37]
Zhang, X.J.; Yu, H.Y.; Cai, Y.; Ke, M. Lycium barbarum polysaccharides inhibit proliferation and migration of bladder cancer cell lines BIU87 by suppressing Pi3K/AKT pathway. Oncotarget,  2017, 8(4), 5936-5942.
 [http://dx.doi.org/10.18632/oncotarget.13963] [PMID: 27992374]

[38]
Zhu, C.P.; Zhang, S.H. Lycium barbarum polysaccharide inhibits the proliferation of HeLa cells by inducing apoptosis. J. Sci. Food Agric.,  2013, 93(1), 149-156.
 [http://dx.doi.org/10.1002/jsfa.5743] [PMID: 22696075]

[39]
Wang, W.; Liu, M.; Wang, Y.; Yang, T.; Li, D.; Ding, F.; Sun, H.; Bai, G.; Li, Q. Lycium barbarum polysaccharide promotes maturation of dendritic cell via notch signaling and strengthens dendritic cell mediated T lymphocyte cytotoxicity on colon cancer cell CT26-WT. Evid. Based Complement. Alternat. Med.,  2018, 2018, 1-10.
 [http://dx.doi.org/10.1155/2018/2305683] [PMID: 29619065]

[40]
Zhang, Q.; Lv, X.; Wu, T.; Ma, Q.; Teng, A.; Zhang, Y.; Zhang, M. Composition of Lycium barbarum polysaccharides and their apoptosis-inducing effect on human hepatoma SMMC-7721 cells. Food Nutr. Res.,  2015, 59(1), 28696.
 [http://dx.doi.org/10.3402/fnr.v59.28696] [PMID: 26563650]

[41]
Chen, S.; Liang, L.; Wang, Y.; Diao, J.; Zhao, C.; Chen, G.; He, Y.; Luo, C.; Wu, X.; Zhang, Y. Synergistic immunotherapeutic effects of Lycium barbarum polysaccharide and interferon-α2b on the murine Renca renal cell carcinoma cell line in vitro and in vivo. Mol. Med. Rep.,  2015, 12(5), 6727-6737.
 [http://dx.doi.org/10.3892/mmr.2015.4230] [PMID: 26300071]

[42]
Zeng, M.; Kong, Q.; Liu, F.; Chen, J.; Sang, H. The anticancer activity of lycium barbarum polysaccharide by inhibiting autophagy in human skin squamous cell carcinoma cells in vitro and in vivo. Int. J. Polym. Sci.,  2019, 1-8.
 [http://dx.doi.org/10.1155/2019/5065920]

[43]
Lou, L.; Chen, G.; Zhong, B.; Liu, F. Lycium barbarum polysaccharide induced apoptosis and inhibited proliferation in infantile hemangioma endothelial cells via down-regulation of PI3K/AKT signaling pathway. Biosci. Rep.,  2019, 39(8), BSR20191182.
 [http://dx.doi.org/10.1042/BSR20191182] [PMID: 31383785]

[44]
Tian, G.Y.; Chen, W.; Feng, Y.C. Isolation, purification and properties of LbGP and characterization of its glycan-peptide bond. Acta Biochim. Biophys. Sin., 1995.

[45]
You, S.; Liu, X.; Xu, G.; Ye, M.; Bai, L.; Lin, R.; Sha, X.; Liang, L.; Huang, J.; Zhou, C.; Rui, W.; Chen, H. Identification of bioactive polysaccharide from Pseudostellaria heterophylla with its anti-inflammatory effects. J. Funct. Foods,  2021, 78, 104353.
 [http://dx.doi.org/10.1016/j.jff.2021.104353]

[46]
Bradford, M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem.,  1976, 72(1-2), 248-254.
 [http://dx.doi.org/10.1016/0003-2697(76)90527-3] [PMID: 942051]

[47]
Li, C.Y.; Chen, H.Y.; Liu, W.P.; Rui, W. Multi-fingerprint profiling combined with chemometric methods for investigating the quality of Astragalus polysaccharides. Int. J. Biol. Macromol.,  2019, 123, 766-774.
 [http://dx.doi.org/10.1016/j.ijbiomac.2018.11.037] [PMID: 30414905]

[48]
Makeeva, D.; Polikarpova, D.; Demyanova, E.; Roshchina, E.; Vakhitov, T.; Kartsova, L. Determination of native amino acids and lactic acid in Lactobacillus helveticusculture media by capillary electrophoresis using Cu2+and β-cyclodextrins as additives. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.,  2020, 1156, 122304.
 [http://dx.doi.org/10.1016/j.jchromb.2020.122304] [PMID: 32829136]

[49]
Tian, G.Y. Study on structure and bioactivity of glycoconjugate compounds of Fructus lycii; World Science Technology-Modernization of Traditional Chinese Medicine, 2003. 

[50]
French, S.W.; Oliva, J.; French, B.A.; Li, J.; Bardag-Gorce, F. Alcohol, nutrition and liver cancer: Role of toll-like receptor signaling. World J. Gastroenterol.,  2010, 16(11), 1344-1348.
 [http://dx.doi.org/10.3748/wjg.v16.i11.1344] [PMID: 20238401]

[51]
Zhang, M.; Tang, X.; Wang, F.; Zhang, Q.; Zhang, Z. Characterization of Lycium barbarum polysaccharide and its effect on human hepatoma cells. Int. J. Biol. Macromol.,  2013, 61, 270-275.
 [http://dx.doi.org/10.1016/j.ijbiomac.2013.06.031] [PMID: 23817098]

[52]
Deng, X.; Luo, S.; Luo, X.; Hu, M.; Ma, F.; Wang, Y.; Lai, X.; Zhou, L. Polysaccharides from Chinese herbal Lycium barbarum induced systemic and local immune responses in H22 tumor-bearing mice. J. Immunol. Res.,  2018, 2018, 1-12.
 [http://dx.doi.org/10.1155/2018/3431782] [PMID: 29967800]

[53]
Deng, X.; Li, X.; Luo, S.; Zheng, Y.; Luo, X.; Zhou, L. Antitumor activity of Lycium barbarum polysaccharides with different molecular weights: an in vitro and in vivo study. Food Nutr. Res.,  2017, 61(1), 1399770.
 [http://dx.doi.org/10.1080/16546628.2017.1399770] [PMID: 31139040]

[54]
Ma, W.; Zhou, Y.; Lou, W.; Wang, B.; Li, B.; Liu, X.; Yang, J.; Yang, B.; Liu, J.; Di, D. Mechanism regulating the inhibition of lung cancer A549 cell proliferation and structural analysis of the polysaccharide Lycium barbarum. Food Biosci.,  2022, 47, 101664.
 [http://dx.doi.org/10.1016/j.fbio.2022.101664]

[55]
Zong, A.; Cao, H.; Wang, F. Anticancer polysaccharides from natural resources: A review of recent research. Carbohydr. Polym.,  2012, 90(4), 1395-1410.
 [http://dx.doi.org/10.1016/j.carbpol.2012.07.026] [PMID: 22944395]

[56]
Mohammad, R.M.; Muqbil, I.; Lowe, L.; Yedjou, C.; Hsu, H.Y.; Lin, L.T.; Siegelin, M.D.; Fimognari, C.; Kumar, N.B.; Dou, Q.P.; Yang, H.; Samadi, A.K.; Russo, G.L.; Spagnuolo, C.; Ray, S.K.; Chakrabarti, M.; Morre, J.D.; Coley, H.M.; Honoki, K.; Fujii, H.; Georgakilas, A.G.; Amedei, A.; Niccolai, E.; Amin, A.; Ashraf, S.S.; Helferich, W.G.; Yang, X.; Boosani, C.S.; Guha, G.; Bhakta, D.; Ciriolo, M.R.; Aquilano, K.; Chen, S.; Mohammed, S.I.; Keith, W.N.; Bilsland, A.; Halicka, D.; Nowsheen, S.; Azmi, A.S. Broad targeting of resistance to apoptosis in cancer. Semin. Cancer Biol.,  2015, 35, S78-S103.
 [http://dx.doi.org/10.1016/j.semcancer.2015.03.001] [PMID: 25936818]

[57]
Kim, S.H.; Yoo, E.S.; Woo, J.S.; Han, S.H.; Lee, J.H.; Jung, S.H.; Kim, H.J.; Jung, J.Y. Antitumor and apoptotic effects of quercetin on human melanoma cells involving JNK/P38 MAPK signaling activation. Eur. J. Pharmacol.,  2019, 860, 172568.
 [http://dx.doi.org/10.1016/j.ejphar.2019.172568] [PMID: 31348906]

[58]
Hirose, T.; Horvitz, H.R. An Sp1 transcription factor coordinates caspase-dependent and -independent apoptotic pathways. Nature,  2013, 500(7462), 354-358.
 [http://dx.doi.org/10.1038/nature12329] [PMID: 23851392]

[59]
Pistritto, G.; Trisciuoglio, D.; Ceci, C.; Garufi, A.; D’Orazi, G. Apoptosis as anticancer mechanism: Function and dysfunction of its modulators and targeted therapeutic strategies. Aging,  2016, 8(4), 603-619.
 [http://dx.doi.org/10.18632/aging.100934] [PMID: 27019364]

[60]
Kashyap, D.; Garg, V.K.; Goel, N. Intrinsic and extrinsic pathways of apoptosis: Role in cancer development and prognosis. Adv. Protein Chem. Struct. Biol.,  2021, 125, 73-120.
 [http://dx.doi.org/10.1016/bs.apcsb.2021.01.003] [PMID: 33931145]

[61]
Sun, Y.; Li, J.; Zhang, Y.; Tu, Y.; Huang, C.; Tao, J.; Yang, M.; Yang, L. The polysaccharide extracted from Umbilicaria esculenta inhibits proliferation of melanoma cells through ros-activated mitochondrial apoptosis pathway. Biol. Pharm. Bull.,  2018, 41(1), 57-64.
 [http://dx.doi.org/10.1248/bpb.b17-00562] [PMID: 29311483]

[62]
Susanti, N.M.P.; Tjahjono, D.H. Cyclin-dependent Kinase 4 and 6 inhibitors in cell cycle dysregulation for breast cancer treatment. Molecules,  2021, 26(15), 4462.
 [http://dx.doi.org/10.3390/molecules26154462] [PMID: 34361615]

[63]
Bury, M.; Le Calvé, B.; Ferbeyre, G.; Blank, V.; Lessard, F. New insights into CDK regulators: Novel opportunities for cancer therapy. Trends Cell Biol.,  2021, 31(5), 331-344.
 [http://dx.doi.org/10.1016/j.tcb.2021.01.010] [PMID: 33676803]

[64]
Tavakolian, S.; Goudarzi, H.; Faghihloo, E. Cyclin-dependent kinases and CDK inhibitors in virus-associated cancers. Infect. Agent. Cancer,  2020, 15(1), 27.
 [http://dx.doi.org/10.1186/s13027-020-00295-7] [PMID: 32377232]

[65]
Bendris, N.; Lemmers, B.; Blanchard, J.M. Cell cycle, cytoskeleton dynamics and beyond: the many functions of cyclins and CDK inhibitors. Cell Cycle,  2015, 14(12), 1786-1798.
 [http://dx.doi.org/10.1080/15384101.2014.998085] [PMID: 25789852]

[66]
da Silva Milhorini, S.; de Lima Bellan, D.; Zavadinack, M.; Simas, F.F.; Smiderle, F.R.; de Santana-Filho, A.P.; Sassaki, G.L.; Iacomini, M. Antimelanoma effect of a fucoxylomannan isolated from Ganoderma lucidum fruiting bodies. Carbohydr. Polym.,  2022, 294, 119823.
 [http://dx.doi.org/10.1016/j.carbpol.2022.119823] [PMID: 35868772]

[67]
Yang, Y.; Zhu, X.; Chen, Y.; Wang, X.; Chen, R. p38 and JNK MAPK, but not ERK1/2 MAPK, play important role in colchicine-induced cortical neurons apoptosis. Eur. J. Pharmacol.,  2007, 576(1-3), 26-33.
 [http://dx.doi.org/10.1016/j.ejphar.2007.07.067] [PMID: 17716651]

[68]
Ballif, B.A.; Blenis, J. Molecular mechanisms mediating mammalian mitogen-activated protein kinase (MAPK) kinase (MEK)-MAPK cell survival signals. Cell Growth Differ.,  2001, 12(8), 397-408.
 [PMID: 11504705]

[69]
Park, H.B.; Baek, K.H. E3 ligases and deubiquitinating enzymes regulating the MAPK signaling pathway in cancers. Biochim. Biophys. Acta Rev. Cancer,  2022, 1877(3), 188736.
 [http://dx.doi.org/10.1016/j.bbcan.2022.188736] [PMID: 35589008]

[70]
Leonardi, G.C.; Falzone, L.; Salemi, R.; Zanghì, A.; Spandidos, D.A.; Mccubrey, J.A.; Candido, S.; Libra, M. Cutaneous melanoma: From pathogenesis to therapy (Review). Int. J. Oncol.,  2018, 52(4), 1071-1080.
 [http://dx.doi.org/10.3892/ijo.2018.4287] [PMID: 29532857]

[71]
Sun, Y.; Liu, W.Z.; Liu, T.; Feng, X.; Yang, N.; Zhou, H.F. Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis. J. Recept. Signal Transduct. Res.,  2015, 35(6), 600-604.
 [http://dx.doi.org/10.3109/10799893.2015.1030412] [PMID: 26096166]

[72]
Xu, T.; Liu, R.; Lu, X.; Wu, X.; Heneberg, P.; Mao, Y.; Jiang, Q.; Loor, J.; Yang, Z. Lycium barbarum polysaccharides alleviate LPS-induced inflammatory responses through PPARγ/MAPK/NF-κB pathway in bovine mammary epithelial cells. J. Anim. Sci.,  2022, 100(1), skab345.
 [http://dx.doi.org/10.1093/jas/skab345] [PMID: 34791267]

[73]
Qin, Y.; Yang, G.; Li, M.; Liu, H.J.; Zhong, W.L.; Yan, X.Q.; Qiao, K.L.; Yang, J.H.; Zhai, D.H.; Yang, W.; Chen, S.; Zhou, H.G.; Sun, T.; Yang, C. Dihydroartemisinin inhibits EMT induced by platinum-based drugs via Akt-Snail pathway. Oncotarget,  2017, 8(61), 103815-103827.
 [http://dx.doi.org/10.18632/oncotarget.21793] [PMID: 29262602]

[74]
Cheung, E.C.; Vousden, K.H. The role of ROS in tumour development and progression. Nat. Rev. Cancer,  2022, 22(5), 280-297.
 [http://dx.doi.org/10.1038/s41568-021-00435-0] [PMID: 35102280]

[75]
Moloney, J.N.; Cotter, T.G. ROS signalling in the biology of cancer. Semin. Cell Dev. Biol.,  2018, 80, 50-64.
 [http://dx.doi.org/10.1016/j.semcdb.2017.05.023] [PMID: 28587975]

[76]
Jin, Y.; Li, Y.; Wang, L.; Fu, X.; Li, C. Physicochemical characterization of a polysaccharide from Rosa roxburghii Tratt fruit and its antitumor activity by activating ROS mediated pathways. Curr. Res. Food Sci.,  2022, 5, 1581-1589.
 [http://dx.doi.org/10.1016/j.crfs.2022.09.016] [PMID: 36161228]

[77]
Guo, C.L.; Wang, L.J.; Zhao, Y.; Liu, H.; Li, X.Q.; Jiang, B.; Luo, J.; Guo, S.J.; Wu, N.; Shi, D.Y. A novel bromophenol derivative BOS-102 induces cell cycle arrest and apoptosis in human A549 lung cancer cells via ROS-mediated PI3K/Akt and the MAPK signaling pathway. Mar. Drugs,  2018, 16(2), 43.
 [http://dx.doi.org/10.3390/md16020043] [PMID: 29370087]
Rights & Permissions Print Cite
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/0118715206274639231103050807	Print ISSN 1871-5206
Publisher Name Bentham Science Publisher	Online ISSN 1875-5992
Anti-Cancer Agents in Medicinal Chemistry

Preparation of Lycium barbarum Active Glycopeptide and Investigation of Its Apoptotic Effects on Melanoma

Abstract Play Pause

Graphical Abstract

Related Journals

Related Books

Abstract
