Gossypin Suppresses Cell Growth by Cytotoxic Effect and Induces Apoptosis in MCF-7 Cells

Yıl 2022, Cilt: 4 Sayı: 1, 21 - 26, 01.01.2022

Mustafa Çiçek , İrfan Çınar , Selin Aksak

https://doi.org/10.37990/medr.996944

Cited By: 1

Öz

Aim: Today, breast cancer is a disease that is encountered commonly in women with limited options for treatment. It is needed to find new agents that can be effective in preventing or managing this disease. It has been demonstrated that gossypin inhibits tumor growth. In our study, it has been targeted to examine the effects of gossypin regarding both anticancer activity and apoptosis in MCF-7 cells.
Material and Method: MCF-7 cells were treated with different doses of gossypin and with 50 µM cisplatin for 24, 48, and 72 hours. The MTT analysis, Caspase-3, Caspase-9, and Nf-KB mRNA expressions of those MCF-7 cells which were treated with gossypin were also conducted in order to evaluate the apoptosis or necroptosis-induced cell death.
Results: In MTT experiments, it has been observed that the administration of 100 µM dose of gossypin had similar effects to the routine cisplatin administration, caused a significant decrease in cell proliferation, and increased apoptosis in the evaluations of Hoechst staining and morphology. It has been put forth that gossypin decreases the expression of CASP-3 and CASP-9 mRNA and increases the expression of NF-kB.
Conclusion: Our results demonstrate that for the breast cancer cells, the 100 µM of gossypin positively affects cell death pathways due to apoptosis. 

Anahtar Kelimeler

gossypin , Apoptosis , Caspase-3 , Caspase-9 , NF-kB

Kaynakça

• 1. Donepudi MS, Kondapalli K, Amos SJ, Venkanteshan P. Breast cancer statistics and markers [Internet]. Vol. 10, Journal of Cancer Research and Therapeutics. Medknow Publications; 2014 [cited 2020 Nov 20]. p. 506–11. Available from: https://pubmed.ncbi.nlm.nih.gov/25313729/
• 2. Ferrini K, Ghelfi F, Mannucci R, Titta L. Lifestyle, nutrition and breast cancer: Facts and presumptions for consideration [Internet]. Vol. 9, ecancermedicalscience. Cancer Intelligence; 2015 [cited 2020 Nov 20]. Available from: https://pubmed.ncbi.nlm.nih.gov/26284121/
• 3. Park SU. Anticancer compounds from plants. EXCLI J [Internet]. 2012 [cited 2020 Nov 20];11:386–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27231469
• 4. Roviello GN, Iannitti R, Roviello V, Palumbo R, Simonyan H, Vicidomini C. Synthesis and biological evaluation of a novel Amadori compound. Amino Acids [Internet]. 2017 Feb 1 [cited 2020 Nov 20];49(2):327–35. Available from: https://pubmed.ncbi.nlm.nih.gov/27864693/
• 5. Taylor WF, Jabbarzadeh E. The use of natural products to target cancer stem cells. Am J Cancer Res [Internet]. 2017 [cited 2020 Nov 20];7(7):1588–605. Available from: www.ajcr.us/
• 6. Gautam P, Flora SJS. Oral supplementation of gossypin during lead exposure protects alteration in heme synthesis pathway and brain oxidative stress in rats. Nutrition. 2010 May 1;26(5):563–70.
• 7. Venkatesan T, Sorimuthu Pillai S. Antidiabetic activity of gossypin, a pentahydroxyflavone glucoside, in streptozotocin-induced experimental diabetes in rats. J Diabetes [Internet]. 2012 Mar [cited 2020 Nov 20];4(1):41–6. Available from: https://pubmed.ncbi.nlm.nih.gov/21722326/
• 8. Bhaskaran S, Dileep K V., Deepa SS, Sadasivan C, Klausner M, Krishnegowda NK, et al. 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 [Internet]. 2013 Apr 1 [cited 2020 Nov 20];12(4):361–72. Available from: www.aacrjournals.org
• 9. Aggarwal BB, Takada Y, Shishodia S, Gutierrez AM, Oommen O V., Ichikawa H, et al. Nuclear transcription factor NF-kappa B: Role in biology and medicine [Internet]. Vol. 42, Indian Journal of Experimental Biology. 2004 [cited 2020 Nov 20]. p. 341–53. Available from: https://europepmc.org/article/med/15088683
• 10. Wang L, Wang X, Chen H, Zu X, Ma F, Liu K, et al. Gossypin inhibits gastric cancer growth by direct targeting of AURKA and RSK2. Phyther Res [Internet]. 2019 Mar 1 [cited 2020 Nov 20];33(3):640–50. Available from: https://pubmed.ncbi.nlm.nih.gov/30536456/
• 11. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin [Internet]. 2018 Nov [cited 2020 Nov 20];68(6):394–424. Available from: https://pubmed.ncbi.nlm.nih.gov/30207593/
• 12. Liao S, Hu X, Liu Z, Lin Y, Liang R, Zhang Y, et al. Synergistic action of microwave-induced mild hyperthermia and paclitaxel in inducing apoptosis in the human breast cancer cell line MCF-7. Oncol Lett [Internet]. 2019 Jan 1 [cited 2020 Nov 20];17(1):603–15. Available from: http://www.spandidos-publications.com/10.3892/ol.2018.9629/abstract
• 13. Shi Y, Zhang L, Liu X, Zhou C, Zhang S, Wang D, et al. Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): A randomised, double-blind phase 3 non-inferiority trial. Lancet Oncol [Internet]. 2013 Sep [cited 2020 Nov 20];14(10):953–61. Available from: https://pubmed.ncbi.nlm.nih.gov/23948351/
• 14. Dasari S, Bernard Tchounwou P. Cisplatin in cancer therapy: Molecular mechanisms of action [Internet]. Vol. 740, European Journal of Pharmacology. Elsevier; 2014 [cited 2020 Nov 20]. p. 364–78. Available from: https://pubmed.ncbi.nlm.nih.gov/25058905/
• 15. Gordaliza M. Natural products as leads to anticancer drugs. Clin Transl Oncol [Internet]. 2007 [cited 2020 Nov 20];9(12):767–76. Available from: https://pubmed.ncbi.nlm.nih.gov/18158980/
• 16. Safarzadeh E, Shotorbani SS, Baradaran B. Herbal medicine as inducers of apoptosis in cancer treatment [Internet]. Vol. 4, Advanced Pharmaceutical Bulletin. Tabriz University of Medical Sciences; 2014 [cited 2020 Nov 20]. p. 421–7. Available from: /pmc/articles/PMC4213780/?report=abstract
• 17. Babu B, Jayram H, Nair M, Ajaikumar KB, Padikkala J. Free radical scavenging, antitumor and anticarcinogenic activity of gossypin. undefined. 2003;
• 18. L P, G N, C C, M G, MT G. Anti-apoptosis and cell survival: a review. Biochim Biophys Acta [Internet]. 2011 Jan [cited 2021 Sep 17];1813(1):238–59. Available from: https://pubmed.ncbi.nlm.nih.gov/20969895/
• 19. Ün Ağrı İbrahim Çeçen Üniversitesi H, Fakültesi E, Anabilim Dalı B, Ün H, Anıl UĞAN R, Çinar İ, et al. Gossypin’in Kato-III Hücrelerindeki Anti-Proliferatif ve Apoptotik Etkilerinin Belirlenmesi. [cited 2021 Sep 17]; Available from: https://dergipark.org.tr/tr/pub/ataunivbd2021;16
• 20. Neise D, Sohn D, Stefanski A, Goto H, Inagaki M, Wesselborg S, et al. The p90 ribosomal S6 kinase (RSK) inhibitor BI-D1870 prevents gamma irradiation-induced apoptosis and mediates senescence via RSK- and p53-independent accumulation of p21WAF1/CIP1. Cell Death Dis [Internet]. 2013 Oct [cited 2020 Nov 25];4(10):e859. Available from: /pmc/articles/PMC3920941/?report=abstract
• 21. Demir M, Cicek M, Eser N, Yoldaş A, Sisman T. Effects of Acute Toluene Toxicity on Different Regions of Rabbit Brain. Anal Cell Pathol. 2017;2017.
• 22. Kong J, Li S, Ma Q, Liu L, Zheng L. Effects of dihydroartemisinin on HSP70 expression in human prostate cancer PC‐3 cells. Andrologia [Internet]. 2019 Jul 10 [cited 2020 Nov 25];51(6):e13280. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1111/and.13280
• 23. Verfaillie T, Garg AD, Agostinis P. Targeting ER stress induced apoptosis and inflammation in cancer. Vol. 332, Cancer Letters. Elsevier Ireland Ltd; 2013. p. 249–64.
• 24. Liu M, Sakamaki T, Casimiro MC, Willmarth NE, Quong AA, Ju X, et al. The canonical NF-κB pathway governs mammary tumorigenesis in transgenic mice and tumor stem cell expansion. Cancer Res [Internet]. 2010 Dec 15 [cited 2020 Nov 25];70(24):10464–73. Available from: /pmc/articles/PMC3010731/?report=abstract