:: Volume 24, Issue 1 (Bimonthly 2020) ::
Feyz 2020, 24(1): 21-30 Back to browse issues page
Comparison of the apoptotic effects of TPSF small molecule and hydroalcoholic extract of Ziziphus spina-christi on cervical cancer cells
Kiavash Hoshmndi , Elham Hoveizi * , Saad Gooraninejad , Mohammadreza Tabandeh
Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, I.R. Iran. , e.hoveizi@yahoo.com
Abstract:   (1587 Views)
Background: Cervical cancer is the third most common cancer in the world. Considering the prevalence of cervical cancer in Iran and unsuccessful treatments, the apoptotic effects of TPSF small molecule investigated in comparison with the hydroelectric extract of Ziziphus Spina-christi leaves on the cervical cancer cell line (HeLa).
Materials and Methods: HeLa cells were cultured in a DMEM medium containing 10% FBS, and treated with different concentrations of TPSF and extract on days 1, 3 and 5. Apoptotic effects were investigated using MTT method, and the morphology of cells was studied by Giemsa staining using invert microscope.
Results: 2 μm concentration of TPSF was determined in 24 hours as IC50 for HeLa cells. The percentage of viability in cells treated with 0.5, 1, 2, 5, and 10 μM TPSF was 78, 63, 50, 42 and 37%. The concentration of 4 mM hydroalcoholic extract was determined as IC50 of HeLa cells in 24 hours. The percentage of viability in treated cells with 1, 2, 4, 6 and 8 mM from the extract of was 73, 61, 50, 41, and 37. The results showed a significant (P≤0.05) decrease compared with the control samples. Also, morphological results showed that the treated cells indicated notable changes such as the shrunk nucleus, damaged membrane, and wrinkled cytoplasm compared with the control sample.
Conclusion: The TPSF is significantly better than the extract of Ziziphus Spina-christi, it can be concluded that small molecules have the smallest amount of cytotoxic effect on HeLa cells and have a greater apoptotic effect.
Keywords: Cervical cancer, Ziziphus Spina-christi leave, TPSF, Small molecule
Full-Text [PDF 489 kb]   (639 Downloads)    
Type of Study: Research | Subject: General
Received: 2019/03/1 | Accepted: 2019/09/29 | Published: 2020/05/16
1. Scott SB, Mogle JA, Sliwinski MJ, Jim HSL, Small BJ. Memory Lapses in Daily Life among Breast Cancer Survivors and Women without Cancer History. Psychooncology 2020.
2. Kemnitzer W, Drewe J, Jiang S, Zhang H, Zhao J, Crogan-Grundy C, et al. Discovery of 4-Aryl-4 H-chromenes as a New Series of Apoptosis Inducers Using a Cell-and CaspaseBased High-Throughput Screening Assay 3. Structure-Activity Relationships of Fused Rings at the 7, 8-Positions. J Med Chem 2007; 50(12): 2858-64.
3. Frelay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN2012. Int J Cancer 2015; 136(5): E359- 86.
4. Moding EJ, Michael BK, Kirsch DG, Strategies for optimizing the Response of Cancer and Normal Tissues to Radiation. Nat Rev Drug Discov 2013; 12(7): 526-42.
5. Brugnoli F, Grassilli S, Benedusi M, Capitani S, Bertagnolo V. RNA interference in the study of molecular mechanisms activated during agonist induced differentiation of acute promyelocytic leukemia derived promyelocytes. Minerva Biotecnol 2008; 20: 39-49.
6. Fossum TW, Hedlund CS, Hulse DA, Johnson AL, Schulz KS, Seim HB, et al. Surgery of the female reproductive tract. In: Fossum TW, Hedlund CS, ditors. Small animal surgery. Mosby, St. Louis, USA 2007; p. 729-35.
7. Harvey HJ. Mammary glands. In: Bojrab MJ and Ellison GW, ditors. Current techniques in small animal surgery. USA 1998; p. 579-84.
8. Zierau O, Helle J, Schadyew S, Morgenroth Y, Bentler M, Hennig A. Role of miR-203 in estrogen receptor-mediated signaling in the rat uterus and endometrial carcinoma. J Cell Biochem 2018; 119: 5359-72.
9. Loi S, Haibe-Kains B, Desmedt C, Lallemand F, Tutt AM, Gillet C, et al. Definition of clinically distinct molecular subtype in estrogen receptor-positive breast carcinomas through genomic grade. J Clin Oncol 2007; 25: 1239-46.
10. Yanuo M, Keiko M, Masaru S, Michiko I, Koushi O. Mechanisms of estrogen receptor-α up-regulation in breast cancers. Med Mol Morphol 2010; 43: 193-6.
11. Lyssiotis CA, Lairson LL, Boitano AE, Wurdak H, Zhu S, Schultz PG. Chemical control of stem cell fate and developmental potential. Angew Chem Int Ed Engl 2011; 50(1): 200-42.
12. Muñoz-Galván S, Felipe-Abrio B, García-Carrasco M, Domínguez-Piñol J, Suarez-Martinez E, Verdugo-Sivianes EM, et al. New markers for human ovarian cancer that link platinum resistance to the cancer stem cell phenotype and define new therapeutic combinations and diagnostic tools. J Exp Clin Cancer Res 2019; 38(1): 234.
13. Bayat N, Ebrahimi-Barough S, Norouzi-Javidan A, Saberi H, Tajerian R, Ardakan MM, et al. Apoptotic effect of atorvastatin in glioblastoma spheroids tumor cultured in fibrin gel. Biomed Pharmacother 2016; 84: 1959-66.
14. Castero-Rivera E, Samudio I, Safe SJ. Estrogen regulation of cyclin D1 gene expression in ZR-75 breast cancer cells involves multiple enhancer element. Biol Chem 2001; 276: 30853-61.
15. Nicole MK, Milu CH, Chengjian M, Irene OA, Philip DR, Rachel S, et al. A noncompetitive small Molecule inhibitor of Esterogen-regulated Gen expression and Breast cancer cell Growth that Enhances proteosom-dependent Degradation of Estrogen Receptor. J Biol Chem 2017; 285(53): 41863-73.
16. Xu HY, Zhang YQ, Liu ZM, Chen T, Lv CY, Tang SH, et al. ETCM: an encyclopaedia of traditional Chinese medicine. Nucleic Acids Res 2019; 47(D1): D976-82.
17. Nesseem DI, Michel CG, Sleem AA, El-Alfy TS. Formulation and evaluation of antihyperglycemic leaf extracts of Zizyphus spinachristi (L.) Wild. Pharmazie 2009; 64(2): 104-9.
18. Peluso I, Miglio C, Morabito G, Ioannone F, Serafini M. Flavonoids and immune function in human: a systematic review. Crit Rev Food Sci Nutr 2015; 55(3): 383-95.
19. Tahergorabi Z, Abedini MR, Mitra M, Fard MH, Beydokhti H. Ziziphus jujuba: A red fruit with promising anticancer activities. Pharmacogn Rev 2015; 9(18): 99-106.
20. Ghobrial I.M, Witzig T.E, and Adjei A.A. Targeting apoptosis pathways in cancer therapy. CA: Cancer J Clin 2005; 55(3): 178-94.
21. Fesik SW. Promoting apoptosis as a strategy for cancer drug discovery. Nat Rev Cancer 2005; 5(11): 876.
22. Plastina P, Bonofiglio D, Vizza D, Fazio A, Rovito D, Giordano C, et al. Identification of bioactive constituents of Ziziphus jujube fruit extracts exerting antiproliferative and apoptotic effects in human breast cancer cells. J Ethnopharmacol 2012; 140(2): 325-32.
23. Frank TF. PI3K/AKT: navigation downstream. Cell 2008; 129(7): 1261-74.
24. Davvid AF, Honyin CH, Benjamin DH, Shubha B, Lewis CC, Robert TA. The PI3K pathway in human Disease. Cell 2017; 170(4): 605-35.
25. Santhi DK, Rajesh M, Wensheng L, Benny AK, Pratima S, Hiltrud B, et al. Mechanism of strogen receptor antagonism toward P53 and its implication in breast cancer therapeutic response and stem cell regulation. Pans 2010; 107(34): 15081-6.
26. Castero-Rivera E, Samudio I, Safe S. Estrogen regulation of cyclin D1gen expression in ZR-75 breast cancer cells involves multiple enhancer element. J Biol Chem 2001; 276: 30853-61.
27. Kretzer NM, Cherian MT, Mao C, Aninye IO, Reynolds PD, Schiff R, et al. A noncompetitive small molecule inhibitor of estrogen-regulated gene expression and breast cancer cell growth that enhances proteasome-dependent degradation of estrogen receptor α. J Biol Chem 2016; 285(53): 41863-73.
28. Hushmandi K, Gooraninejad S , Hoveizi E, Tabandeh MR. Growth Inhibitory and Anti-Proliferative Effects of S14161 Small Molecule on Hela Cervical Cancer Cell in Hydrogel Scaffold 2019: 132. Available at: www.Personalized Medicine Journal.com
29. Hoshyar R, Jamali S, Fereidouni M, Abedini MR. The cytotoxic activity of Ziziphus Jujube on cervical cancer cells: In Vitro study. Cell Mol Biol 2015; 30: 61(8): 128-30.
30. Guizani N, Waly MI, Singh V, Rahman MS. Nabag (Zizyphus spina-christi) extract prevents aberrant crypt foci development in colons of azoxymethane-treated rats by abrogating oxidative stress and inducing apoptosis. Asian Pac J Cancer Prev 2013; 14(9): 5031-5.
31. Jafarian A, Zolfaghari B, Shirani K. Cytotoxicity of different extracts of aerial parts of Ziziphus spina-christi on Hela and MDA-MB468 tumor cells. Adv Biomed Res 2014; 3: 38.
32. Xu MY, Lee SY, Kang SS, Kim YS. Antitumor activity of jujuboside B and the underlying mechanism via induction of apoptosis and autophagy. J Nat Prod 2014; 77(2): 370-6.
33. Ahmadi R, Rahimi S, Ehteshamzad N. The effect of hydroalcoholic Ziziphus spina-christi leaf extract on viability of breast cancer cell line (MCF7) and evaluation of Bax and Bcl2 genes expression level. Feyz 2017; 21(5): 406-12. [in Persian]
34. Soliman S, Hamoda AM, El-Shorbagi AA, El-Keblawy AA. Novel betulin derivative is responsible for the anticancer folk use of Ziziphus spina-christi from the hot environmental habitat of UAE. J Ethnopharmacol 2108; 1(231): 403-8.

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