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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

Apoptosis-Inducing Activity and Antiproliferative Effect of Gossypin on PC-3 Prostate Cancer Cells

Author(s): Irfan Cinar*

Volume 21, Issue 4, 2021

Published on: 21 July, 2020

Page: [445 - 450] Pages: 6

DOI: 10.2174/1871520620666200721103422

Price: $65

Abstract

Aim: The rapid growth, morbidity and mortality of prostate cancer, and the lack of effective treatment have attracted great interest of researchers to find novel cancer therapies aiming at the effect of gossypin on cell proliferation and apoptosis of PC-3 cells.

Methods: The effect of gossypin on cell viability was determined using MTT assay at 5-100μg/ml and cisplatin (50μM) in a time-dependent manner in PC-3 cell lines. The expression levels of caspase-3 (CASP3) and caspase-9 (CASP9) for apoptosis and Nuclear Factor Kappa B (NFKB1) for survival, inflammation, and growth were evaluated by real-time PCR. Hoechst staining was used to analyze apoptosis.

Results: Gossypin showed an anti-proliferative effect on PC3 cell line in a time- and dose-dependent manner. In addition, gossypin led to a significant increase in apoptosis genes (CASP3, CASP9) when compared to control while it caused a decrease in the level of NFKB1, which is accepted as apoptosis inhibitor (p<0.05) (cisplatin-like). Gossypin 50 and 100μM significantly induced apoptotic mechanism in PC-3 cells. However, no apoptotic or commonly stained nuclei have been observed in control group cells.

Conclusion: The results indicated that gossypin can be defined as a promising anticancer agent for PC-3 human prostate cancer cell line.

Keywords: Gossypin, anticancer, prostate cancer cells (PC-3), apoptosis, caspase, MTT assay.

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[1]
Mateo, J.; Carreira, S.; Sandhu, S.; Miranda, S.; Mossop, H.; Perez-Lopez, R.; Nava Rodrigues, D.; Robinson, D.; Omlin, A.; Tunariu, N.; Boysen, G.; Porta, N.; Flohr, P.; Gillman, A.; Figueiredo, I.; Paulding, C.; Seed, G.; Jain, S.; Ralph, C.; Protheroe, A.; Hussain, S.; Jones, R.; Elliott, T.; McGovern, U.; Bianchini, D.; Goodall, J.; Zafeiriou, Z.; Williamson, C.T.; Ferraldeschi, R.; Riisnaes, R.; Ebbs, B.; Fowler, G.; Roda, D.; Yuan, W.; Wu, Y.M.; Cao, X.; Brough, R.; Pemberton, H.; A’Hern, R.; Swain, A.; Kunju, L.P.; Eeles, R.; Attard, G.; Lord, C.J.; Ashworth, A.; Rubin, M.A.; Knudsen, K.E.; Feng, F.Y.; Chinnaiyan, A.M.; Hall, E.; de Bono, J.S. DNA-repair defects and olaparib in metastatic prostate cancer. N. Engl. J. Med., 2015, 373(18), 1697-1708.
[http://dx.doi.org/10.1056/NEJMoa1506859] [PMID: 26510020]
[2]
Lavery, H.J.; Cooperberg, M.R. Clinically localized prostate cancer in 2017: A review of comparative effectiveness. Urol. Oncol., 2017, 35(2), 40-41.
[http://dx.doi.org/10.1016/j.urolonc.2016.11.013] [PMID: 27998677]
[3]
Park, S.U. Anticancer compounds from plants. EXCLI J., 2012, 11, 386-389.
[PMID: 27231469]
[4]
Roviello, G.N.; Iannitti, R.; Palumbo, R.; Simonyan, H.; Vicidomini, C.; Roviello, V. Lac-L-TTA, a novel lactose-based amino acid-sugar conjugate for anti-metastatic applications. Amino Acids, 2017, 49(8), 1347-1353.
[http://dx.doi.org/10.1007/s00726-017-2433-2] [PMID: 28478584]
[5]
Roviello, G.N.; Iannitti, R.; Roviello, V.; Palumbo, R.; Simonyan, H.; Vicidomini, C. Synthesis and biological evaluation of a novel Amadori compound. Amino Acids, 2017, 49(2), 327-335.
[http://dx.doi.org/10.1007/s00726-016-2363-4] [PMID: 27864693]
[6]
Tomimori, K.; Nakama, S.; Kimura, R.; Tamaki, K.; Ishikawa, C.; Mori, N. Antitumor activity and macrophage nitric oxide producing action of medicinal herb, Crassocephalum crepidioides. BMC Complement. Altern. Med., 2012, 12, 78.
[http://dx.doi.org/10.1186/1472-6882-12-78] [PMID: 22720874]
[7]
Luqman, S.; Pezzuto, J.M. NFkappaB: A promising target for natural products in cancer chemoprevention. Phytother. Res., 2010, 24(7), 949-963.
[PMID: 20577970]
[8]
Kosem, N.; Ichikawa, K.; Utsumi, H.; Moongkarndi, P. In vivo toxicity and antitumor activity of mangosteen extract. J. Nat. Med., 2013, 67(2), 255-263.
[http://dx.doi.org/10.1007/s11418-012-0673-8] [PMID: 22622784]
[9]
Taylor, W.F.; Jabbarzadeh, E. The use of natural products to target cancer stem cells. Am. J. Cancer Res., 2017, 7(7), 1588-1605.
[PMID: 28744407]
[10]
Ishibashi, M.; Ohtsuki, T. Studies on search for bioactive natural products targeting TRAIL signaling leading to tumor cell apoptosis. Med. Res. Rev., 2008, 28(5), 688-714.
[http://dx.doi.org/10.1002/med.20123] [PMID: 18273883]
[11]
Vijayan, P.; Raghu, C.; Ashok, G.; Dhanaraj, S.A.; Suresh, B. Antiviral activity of medicinal plants of Nilgiris. Indian J. Med. Res., 2004, 120(1), 24-29.
[PMID: 15299228]
[12]
Gautam, P.; Flora, S.J. Oral supplementation of gossypin during lead exposure protects alteration in heme synthesis pathway and brain oxidative stress in rats. Nutrition, 2010, 26(5), 563-570.
[http://dx.doi.org/10.1016/j.nut.2009.06.008] [PMID: 19647414]
[13]
Venkatesan, T.; Sorimuthu Pillai, S. Antidiabetic activity of gossypin, a pentahydroxyflavone glucoside, in streptozotocin-induced experimental diabetes in rats. J. Diabetes, 2012, 4(1), 41-46.
[http://dx.doi.org/10.1111/j.1753-0407.2011.00145.x] [PMID: 21722326]
[14]
Viswanathan, S.; Sambantham, P.T.; Reddy, K.; Kameswaran, L. Gossypin-induced analgesia in mice. Eur. J. Pharmacol., 1984, 98(2), 289-291.
[http://dx.doi.org/10.1016/0014-2999(84)90604-6] [PMID: 6325219]
[15]
Yoon, I.; Lee, K.H.; Cho, J. Gossypin protects primary cultured rat cortical cells from oxidative stress- and beta-amyloid-induced toxicity. Arch. Pharm. Res., 2004, 27(4), 454-459.
[http://dx.doi.org/10.1007/BF02980089] [PMID: 15180313]
[16]
Ramaswamy, S.; Viswanathan, S. Influence of gossypin on the development of acute tolerance to morphine induced antinociception. Indian J. Exp. Biol., 1997, 35(4), 413-414.
[PMID: 9315244]
[17]
Añón, M.T.; Ubeda, A.; Alcaraz, M.J. Protective effects of phenolic compounds on CCl4-induced toxicity in isolated rat hepatocytes. Z. Natforsch. C J. Biosci., 1992, 47(3-4), 275-279.
[http://dx.doi.org/10.1515/znc-1992-3-417] [PMID: 1590889]
[18]
Vijayaraghavan, R.; Sugendran, K.; Pant, S.C.; Husain, K.; Malhotra, R.C. Dermal intoxication of mice with bis(2-chloroethyl)sulphide and the protective effect of flavonoids. Toxicology, 1991, 69(1), 35-42.
[http://dx.doi.org/10.1016/0300-483X(91)90151-P] [PMID: 1926154]
[19]
Cinar, I.; Sirin, B.; Aydin, P.; Toktay, E.; Cadirci, E.; Halici, I.; Halici, Z. Ameliorative effect of gossypin against acute lung injury in experimental sepsis model of rats. Life Sci., 2019, 221, 327-334.
[http://dx.doi.org/10.1016/j.lfs.2019.02.039] [PMID: 30797018]
[20]
Babu, B.H.; Jayram, H.N.; Nair, M.G.; Ajaikumar, K.B.; Padikkala, J. Free radical scavenging, antitumor and anticarcinogenic activity of gossypin. J. Exp. Clin. Cancer Res., 2003, 22(4), 581-589.
[PMID: 15053300]
[21]
Kunnumakkara, A.B.; Nair, A.S.; Ahn, K.S.; Pandey, M.K.; Yi, Z.; Liu, M.; Aggarwal, B.B. Gossypin, a pentahydroxy glucosyl flavone, inhibits the transforming growth factor beta-activated kinase-1-mediated NF-kappaB activation pathway, leading to potentiation of apoptosis, suppression of invasion, and abrogation of osteoclastogenesis. Blood, 2007, 109(12), 5112-5121.
[http://dx.doi.org/10.1182/blood-2007-01-067256] [PMID: 17332240]
[22]
Bhaskaran, S.; Dileep, K.V.; Deepa, S.S.; Sadasivan, C.; Klausner, M.; Krishnegowda, N.K.; Tekmal, R.R.; VandeBerg, J.L.; Nair, H.B. Gossypin as a novel selective dual inhibitor of V-RAF murine sarcoma viral oncogene homolog B1 and cyclin-dependent kinase 4 for melanoma. Mol. Cancer Ther., 2013, 12(4), 361-372.
[http://dx.doi.org/10.1158/1535-7163.MCT-12-0965] [PMID: 23543365]
[23]
Aggarwal, B.B.; Takada, Y.; Shishodia, S.; Gutierrez, A.M.; Oommen, O.V.; Ichikawa, H.; Baba, Y.; Kumar, A. Nuclear transcription factor NF-kappa B: Role in biology and medicine. Indian J. Exp. Biol., 2004, 42(4), 341-353.
[PMID: 15088683]
[24]
Adams, J.M.; Cory, S. Apoptosomes: Engines for caspase activation. Curr. Opin. Cell Biol., 2002, 14(6), 715-720.
[http://dx.doi.org/10.1016/S0955-0674(02)00381-2] [PMID: 12473344]
[25]
Palabiyik, S.S.; Karakus, E.; Halici, Z.; Cadirci, E.; Bayir, Y.; Ayaz, G.; Cinar, I. The protective effects of carvacrol and thymol against paracetamol-induced toxicity on human hepatocellular carcinoma cell lines (HepG2). Hum. Exp. Toxicol., 2016, 35(12), 1252-1263.
[http://dx.doi.org/10.1177/0960327115627688] [PMID: 26801986]
[26]
Shi, Y.; Zhang, L.; Liu, X.; Zhou, C.; Zhang, L.; Zhang, S.; Wang, D.; Li, Q.; Qin, S.; Hu, C.; Zhang, Y.; Chen, J.; Cheng, Y.; Feng, J.; Zhang, H.; Song, Y.; Wu, Y.L.; Xu, N.; Zhou, J.; Luo, R.; Bai, C.; Jin, Y.; Liu, W.; Wei, Z.; Tan, F.; Wang, Y.; Ding, L.; Dai, H.; Jiao, S.; Wang, J.; Liang, L.; Zhang, W.; Sun, Y. Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): A randomised, double-blind phase 3 non-inferiority trial. Lancet Oncol., 2013, 14(10), 953-961.
[http://dx.doi.org/10.1016/S1470-2045(13)70355-3] [PMID: 23948351]
[27]
Dasari, S.; Tchounwou, P.B. Cisplatin in cancer therapy: Molecular mechanisms of action. Eur. J. Pharmacol., 2014, 740, 364-378.
[http://dx.doi.org/10.1016/j.ejphar.2014.07.025] [PMID: 25058905]
[28]
Ju, S.M.; Kang, J.G.; Bae, J.S.; Pae, H.O.; Lyu, Y.S.; Jeon, B.H. The flavonoid apigenin ameliorates cisplatin-induced nephrotoxicity through reduction of p53 activation and promotion of PI3K/Akt pathway in human renal proximal tubular epithelial cells. Evid. Based Complement. Alternat. Med., 2015, 2015186436
[http://dx.doi.org/10.1155/2015/186436] [PMID: 26089934]
[29]
Haghi, A.; Azimi, H.; Rahimi, R. A comprehensive review on pharmacotherapeutics of three phytochemicals, curcumin, quercetin, and allicin, in the treatment of gastric cancer. J. Gastrointest. Cancer, 2017, 48(4), 314-320.
[http://dx.doi.org/10.1007/s12029-017-9997-7] [PMID: 28828709]
[30]
Gordaliza, M. Natural products as leads to anticancer drugs. Clin. Transl. Oncol., 2007, 9(12), 767-776.
[http://dx.doi.org/10.1007/s12094-007-0138-9] [PMID: 18158980]
[31]
Li, Y.; Ellis, K.L.; Ali, S.; El-Rayes, B.F.; Nedeljkovic-Kurepa, A.; Kucuk, O.; Philip, P.A.; Sarkar, F.H. Apoptosis-inducing effect of chemotherapeutic agents is potentiated by soy isoflavone genistein, a natural inhibitor of NF-kappaB in BxPC-3 pancreatic cancer cell line. Pancreas, 2004, 28(4), e90-e95.
[http://dx.doi.org/10.1097/00006676-200405000-00020] [PMID: 15097869]
[32]
Safarzadeh, E.; Sandoghchian Shotorbani, S.; Baradaran, B. Herbal medicine as inducers of apoptosis in cancer treatment. Adv. Pharm. Bull., 2014, 4(Suppl. 1), 421-427.
[PMID: 25364657]
[33]
Çınar, I.; Karakuş, E.; Şengül, E.; Gelen, V.; Bayır, Y.; Halıcı, Z.; Karameşe, M.; Sevim, Ç.; Özel, B.; Kardeş, S. Gossypin inhibits lipopolysaccharide-induced inflammatory response in human umbilical vein endothelial cells. Toxicol. Lett., 2016, 258, 290.
[http://dx.doi.org/10.1016/j.toxlet.2016.06.2009]
[34]
Haddad, A.Q.; Venkateswaran, V.; Viswanathan, L.; Teahan, S.J.; Fleshner, N.E.; Klotz, L.H. Novel antiproliferative flavonoids induce cell cycle arrest in human prostate cancer cell lines. Prostate Cancer Prostatic Dis., 2006, 9(1), 68-76.
[http://dx.doi.org/10.1038/sj.pcan.4500845] [PMID: 16314891]
[35]
Jiang, Z.; Akhtar, Y.; Bradbury, R.; Zhang, X.; Isman, M.B. Comparative toxicity of essential oils of Litsea pungens and Litsea cubeba and blends of their major constituents against the cabbage looper, Trichoplusia ni. J. Agric. Food Chem., 2009, 57(11), 4833-4837.
[http://dx.doi.org/10.1021/jf900274r] [PMID: 19422220]
[36]
Hunter, A.M.; LaCasse, E.C.; Korneluk, R.G. The Inhibitors of Apoptosis (IAPs) as cancer targets. Apoptosis,, 2007, 12(9), 1543-1568.
[http://dx.doi.org/10.1007/s10495-007-0087-3] [PMID: 17573556]
[37]
Wang, J.; Lenardo, M.J. Roles of caspases in apoptosis, development, and cytokine maturation revealed by homozygous gene deficiencies. J. Cell Sci., 2000, 113(Pt 5), 753-757.
[PMID: 10671365]
[38]
Amanpour, P.; Khodarahmi, P.; Salehipour, M. Protective effects of vitamin E on cadmium-induced apoptosis in rat testes. Naunyn Schmiedebergs Arch. Pharmacol., 2020, 393(3), 349-358.
[PMID: 31620823]
[39]
Ola, M.S.; Nawaz, M.; Ahsan, H. Role of Bcl-2 family proteins and caspases in the regulation of apoptosis. Mol. Cell. Biochem., 2011, 351(1-2), 41-58.
[http://dx.doi.org/10.1007/s11010-010-0709-x] [PMID: 21210296]
[40]
Slee, E.A.; Adrain, C.; Martin, S.J. Executioner caspase-3, -6, and -7 perform distinct, non-redundant roles during the demolition phase of apoptosis. J. Biol. Chem., 2001, 276(10), 7320-7326.
[http://dx.doi.org/10.1074/jbc.M008363200] [PMID: 11058599]
[41]
Kong, J.; Li, S.S.; Ma, Q.; Liu, L.; Zheng, L.J. Effects of dihydroartemisinin on HSP70 expression in human prostate cancer PC-3 cells. Andrologia, 2019, 51(6)e13280
[http://dx.doi.org/10.1111/and.13280]] [PMID: 30972796]
[42]
Paule, B.; Terry, S.; Kheuang, L.; Soyeux, P.; Vacherot, F.; de la Taille, A. The NF-kappaB/IL-6 pathway in metastatic androgen-independent prostate cancer: New therapeutic approaches? World J. Urol., 2007, 25(5), 477-489.
[http://dx.doi.org/10.1007/s00345-007-0175-6] [PMID: 17541600]
[43]
Sambantham, S.; Radha, M.; Paramasivam, A.; Anandan, B.; Malathi, R.; Chandra, S.R.; Jayaraman, G. Molecular mechanism underlying hesperetin-induced apoptosis by in silico analysis and in prostate cancer PC-3 cells. Asian Pac. J. Cancer Prev., 2013, 14(7), 4347-4352.
[http://dx.doi.org/10.7314/APJCP.2013.14.7.4347] [PMID: 23992001]
[44]
Shukla, S.; Gupta, S. Suppression of constitutive and tumor necrosis factor alpha-induced Nuclear Factor (NF)-kappaB activation and induction of apoptosis by apigenin in human prostate carcinoma PC-3 cells: Correlation with down-regulation of NF-kappaB-responsive genes. Clin. Cancer Res., 2004, 10(9), 3169-3178.
[http://dx.doi.org/10.1158/1078-0432.CCR-03-0586] [PMID: 15131058]
[45]
Ross, J.S.; Kallakury, B.V.; Sheehan, C.E.; Fisher, H.A.; Kaufman, R.P., Jr; Kaur, P.; Gray, K.; Stringer, B. Expression of nuclear factor-kappa B and I kappa B alpha proteins in prostatic adenocarcinomas: correlation of nuclear factor-kappa B immunoreactivity with disease recurrence. Clin. Cancer Res., 2004, 10(7), 2466-2472.
[http://dx.doi.org/10.1158/1078-0432.CCR-0543-3] [PMID: 15073126]
[46]
Xie, J.H.; Lai, Z.Q.; Zheng, X.H.; Xian, Y.F.; Li, Q.; Ip, S.P.; Xie, Y.L.; Chen, J.N.; Su, Z.R.; Lin, Z.X.; Yang, X.B. Apoptosis induced by bruceine D in human non small cell lung cancer cells involves mitochondrial ROS mediated death signaling. Int. J. Mol. Med., 2019, 44(6), 2015-2026.
[http://dx.doi.org/10.3892/ijmm.2019.4363] [PMID: 31638181]
[47]
Wang, L.; Liu, C.; Li, C.; Xue, J.; Zhao, S.; Zhan, P.; Lin, Y.; Zhang, P.; Jiang, A.; Chen, W. Effects of microRNA-221/222 on cell proliferation and apoptosis in prostate cancer cells. Gene, 2015, 572(2), 252-258.
[http://dx.doi.org/10.1016/j.gene.2015.07.017] [PMID: 26164758]

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