Yıl: 2023 Cilt: 12 Sayı: 1 Sayfa Aralığı: 20 - 25 Metin Dili: İngilizce DOI: 10.5455/medscience.2022.11.251 İndeks Tarihi: 29-05-2023

Anticancer activity of Heat Shock Protein 70 (HSP70) Inhibitor, JG-98, against human cervical cancer HeLa and ovarian cancer SKOV-3 cells

Öz:
Cervical and ovarian cancer are two aggressive neoplasms for women, still with high mortality and morbidity. Among the molecules and compounds that have anticancer activity, it was studied the JG-98, a heat shock protein 70 (HSP70) inhibitor. It demonstrated inhibitory effects on the growth of neoplastic cells, mediated by the induction of apoptosis, with anti-proliferation activity on neoplastic cells via the apoptotic pathway. The authors investigated the antiproliferative effects of JG-98 on human cervical cancer HeLa and ovarian cancer SKOV-3, examined by a standard XTT assay. Apoptotic effects and oxidative status were also evaluated by flow cytometry, ELISA, and total oxidant status assays in HeLa cells, respectively. The IC50 values of JG-98 in HeLa and SKOV-3 cells were recorded as 1.79 and 2.96 μM, respectively. Flow cytometry results showed that JG-98 treatment remarkably increased the proportion of apoptotic cells at IC50 concentration. The JG-98 treatment significantly increased the proteins Bax, cleaved caspase 3, cleaved PARP, and 8-oxo-dG levels, all indicators of cellular apoptosis. These findings show that JG-98 significantly decreased cell proliferation and increased apoptosis in HeLa cells, suggesting that JG-98 has a promising anti-tumor effect in cervical and ovarian cancers.
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  • 1. Zhou Y, Espenel S, Achkar S, et al. Combined modality including novel sensitizers in gynecological cancers. Int J Gynecol Cancer. 2022;32:389- 401.
  • 2. Harbin LM, Gallion HH, Allison DB, Kolesar JM. Next generation sequencing and molecular biomarkers in ovarian cancer-An opportunity for targeted therapy. Diagnostics. 2022;12:842.
  • 3. Sumi MP, Ghosh A. Hsp90 in Human Diseases: Molecular Mechanisms to Therapeutic Approaches. Cells. 2022;11:976.
  • 4. Albakova Z, Armeev GA, Kanevskiy LM, et al. HSP70 Multi- Functionality in Cancer. Cells. 2020;3;9:587.
  • 5. Zheng S, Liang Y, Li L, et al. Revisiting the Old Data of Heat Shock Protein 27 Expression in Squamous Cell Carcinoma: Enigmatic HSP27, More Than Heat Shock. Cells. 2022;11:1665.
  • 6. Anand U, Dey A, Chandel AKS, et al. Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics. Genes Dis. 21 February 2022.
  • 7. Ciocca DR, Calderwood SK. Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones. 2005;10:86-103.
  • 8. Håvik B, Bramham CR. Additive viability-loss following hsp70/hsc70 double interference and Hsp90 inhibition in two breast cancer cell lines. Oncol Rep. 2007;17:1501–10.
  • 9. Ibrahim S, Putra A, Amalina ND, Nasution IPA. Heat shock protein-70 expression in CSCs tumor-associated macrophages induced by Typhonium flagelliforme tuber extract. J Appl Pharm Sci. 2022;12:146–52.
  • 10. Martínez-Esquivias F, Gutiérrez-Angulo M, Pérez-Larios A, et al. Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics. Genes Dis.. Anticancer activity of selenium nanoparticles in vitro studies. Anti-Cancer Agents Med Chem (Formerly Curr Med Chem Agents). 2022;22:1658-73.
  • 11. Ray S, Lu Y, Kaufmann SH, et al. Genomic mechanisms of p210BCR- ABL signaling: induction of heat shock protein 70 through the GATA response element confers resistance to paclitaxel-induced apoptosis. J Biol Chem. 2004;8;279:35604–15.
  • 12. Radons J. The human HSP70 family of chaperones: where do we stand? Cell Stress Chaperones. 2016;5;21:379-404.
  • 13. El-Far YM, Khodir AE, Noor AO, et al. Selective cytotoxic activity and protective effects of sodium ascorbate against hepatocellular carcinoma through its effect on oxidative stress and apoptosis in vivo and in vitro. Redox Rep. 2020;25:17-25.
  • 14. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005;38:1103-11.
  • 15. Lin CN, Tsai YC, Hsu CC, et al. An aptamer interacting with heat shock protein 70 shows therapeutic effects and prognostic ability in serous ovarian cancer. Mol Ther Nucleic Acids. 2021;3;23:757-68.
  • 16. Murphy ME. The HSP70 family and cancer. Carcinogenesis. 2013;34:1181-8.
  • 17. Kurashova NA, Madaeva IM, Kolesnikova LI. [Expression of heat shock proteins HSP70 under oxidative stress.]. Adv Gerontol =Uspekhi Gerontol. 2019;32:502-8.
  • 18. Goloudina AR, Demidov ON, Garrido C. Inhibition of HSP70: A challenging anti-cancer strategy. Cancer Lett [Internet]. 2012;325:117-24.
  • 19. Elmallah MIY, Cordonnier M, Vautrot V, et al. Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics. Genes Dis. Membrane-anchored heat-shock protein 70 (Hsp70) in cancer. Cancer Lett 2020;469:134–41.
  • 20. Liu J, Liu J, Guo SY, et al. HSP70 inhibitor combined with cisplatin suppresses the cervical cancer proliferation in vitro and transplanted tumor growth: An experimental study. Asian Pac J Trop Med. 2017;2;10:184–8.
  • 21. Garg M, Kanojia D, Saini S, et al. Germ cell-specific heat shock protein 70-2 is expressed in cervical carcinoma and is involved in the growth, migration, and invasion of cervical cells. Cancer. 2010;8;116:3785–96.
  • 22. Court KA, Hatakeyama H, Wu SY, et al. HSP70 Inhibition Synergistically Enhances the Effects of Magnetic Fluid Hyperthermia in Ovarian Cancer. Mol Cancer Ther. 2017;16:966–76.
  • 23. Oliveira DVNP, Prahm KP, Christensen IJ, te al. Gene expression profile association with poor prognosis in epithelial ovarian cancer patients. Sci Rep. 2021;3;11:5438.
  • 24. Rinaldi S, Assimon VA, Young ZT, et al. A Local Allosteric Network in Heat Shock Protein 70 (Hsp70) Links Inhibitor Binding to Enzyme Activity and Distal Protein-Protein Interactions. ACS Chem Biol. 2018; 13:3142–52.
  • 25. Li X, Colvin T, Rauch JN, et al. Validation of the Hsp70-Bag3 protein- protein interaction as a potential therapeutic target in cancer. Mol Cancer Ther. 2015;14:642–8.
  • 26. Li X, Srinivasan SR, Connarn J, et al. Analogs of the Allosteric Heat Shock Protein 70 (Hsp70) Inhibitor, MKT-077, as Anti-Cancer Agents. ACS Med Chem Lett. 2013;4:1042–7.
  • 27. Kudryavtsev VA, Khokhlova A V, Mosina VA, et al. Induction of Hsp70 in tumor cells treated with inhibitors of the Hsp90 activity: A predictive marker and promising target for radiosensitization. PLoS One. 2017;12:e0173640.
  • 28. Juhasz K, Lipp A-M, Nimmervoll B, et al. The complex function of hsp70 in metastatic cancer. Cancers (Basel). 2013;12;6:42–66.
  • 29. Hoter A, Naim HY. Heat Shock Proteins and Ovarian Cancer: Important Roles and Therapeutic Opportunities. Cancers (Basel). 2019;11:1389.
  • 30. Li X-F, Hua T, Li Y, et al. The HSP70 gene predicts prognosis and response to chemotherapy in epithelial ovarian cancer. Ann Transl Med. 2021;5;9:806.
APA YURTCU N, Karademir D, Ergül M, Cetin A, Tinelli A (2023). Anticancer activity of Heat Shock Protein 70 (HSP70) Inhibitor, JG-98, against human cervical cancer HeLa and ovarian cancer SKOV-3 cells. , 20 - 25. 10.5455/medscience.2022.11.251
Chicago YURTCU NAZAN,Karademir Dilay,Ergül Mustafa,Cetin Ali,Tinelli Andrea Anticancer activity of Heat Shock Protein 70 (HSP70) Inhibitor, JG-98, against human cervical cancer HeLa and ovarian cancer SKOV-3 cells. (2023): 20 - 25. 10.5455/medscience.2022.11.251
MLA YURTCU NAZAN,Karademir Dilay,Ergül Mustafa,Cetin Ali,Tinelli Andrea Anticancer activity of Heat Shock Protein 70 (HSP70) Inhibitor, JG-98, against human cervical cancer HeLa and ovarian cancer SKOV-3 cells. , 2023, ss.20 - 25. 10.5455/medscience.2022.11.251
AMA YURTCU N,Karademir D,Ergül M,Cetin A,Tinelli A Anticancer activity of Heat Shock Protein 70 (HSP70) Inhibitor, JG-98, against human cervical cancer HeLa and ovarian cancer SKOV-3 cells. . 2023; 20 - 25. 10.5455/medscience.2022.11.251
Vancouver YURTCU N,Karademir D,Ergül M,Cetin A,Tinelli A Anticancer activity of Heat Shock Protein 70 (HSP70) Inhibitor, JG-98, against human cervical cancer HeLa and ovarian cancer SKOV-3 cells. . 2023; 20 - 25. 10.5455/medscience.2022.11.251
IEEE YURTCU N,Karademir D,Ergül M,Cetin A,Tinelli A "Anticancer activity of Heat Shock Protein 70 (HSP70) Inhibitor, JG-98, against human cervical cancer HeLa and ovarian cancer SKOV-3 cells." , ss.20 - 25, 2023. 10.5455/medscience.2022.11.251
ISNAD YURTCU, NAZAN vd. "Anticancer activity of Heat Shock Protein 70 (HSP70) Inhibitor, JG-98, against human cervical cancer HeLa and ovarian cancer SKOV-3 cells". (2023), 20-25. https://doi.org/10.5455/medscience.2022.11.251
APA YURTCU N, Karademir D, Ergül M, Cetin A, Tinelli A (2023). Anticancer activity of Heat Shock Protein 70 (HSP70) Inhibitor, JG-98, against human cervical cancer HeLa and ovarian cancer SKOV-3 cells. Medicine Science, 12(1), 20 - 25. 10.5455/medscience.2022.11.251
Chicago YURTCU NAZAN,Karademir Dilay,Ergül Mustafa,Cetin Ali,Tinelli Andrea Anticancer activity of Heat Shock Protein 70 (HSP70) Inhibitor, JG-98, against human cervical cancer HeLa and ovarian cancer SKOV-3 cells. Medicine Science 12, no.1 (2023): 20 - 25. 10.5455/medscience.2022.11.251
MLA YURTCU NAZAN,Karademir Dilay,Ergül Mustafa,Cetin Ali,Tinelli Andrea Anticancer activity of Heat Shock Protein 70 (HSP70) Inhibitor, JG-98, against human cervical cancer HeLa and ovarian cancer SKOV-3 cells. Medicine Science, vol.12, no.1, 2023, ss.20 - 25. 10.5455/medscience.2022.11.251
AMA YURTCU N,Karademir D,Ergül M,Cetin A,Tinelli A Anticancer activity of Heat Shock Protein 70 (HSP70) Inhibitor, JG-98, against human cervical cancer HeLa and ovarian cancer SKOV-3 cells. Medicine Science. 2023; 12(1): 20 - 25. 10.5455/medscience.2022.11.251
Vancouver YURTCU N,Karademir D,Ergül M,Cetin A,Tinelli A Anticancer activity of Heat Shock Protein 70 (HSP70) Inhibitor, JG-98, against human cervical cancer HeLa and ovarian cancer SKOV-3 cells. Medicine Science. 2023; 12(1): 20 - 25. 10.5455/medscience.2022.11.251
IEEE YURTCU N,Karademir D,Ergül M,Cetin A,Tinelli A "Anticancer activity of Heat Shock Protein 70 (HSP70) Inhibitor, JG-98, against human cervical cancer HeLa and ovarian cancer SKOV-3 cells." Medicine Science, 12, ss.20 - 25, 2023. 10.5455/medscience.2022.11.251
ISNAD YURTCU, NAZAN vd. "Anticancer activity of Heat Shock Protein 70 (HSP70) Inhibitor, JG-98, against human cervical cancer HeLa and ovarian cancer SKOV-3 cells". Medicine Science 12/1 (2023), 20-25. https://doi.org/10.5455/medscience.2022.11.251