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The Anti-proliferative Effect of Caffeic Acid and Dactolisib on Human Cervical Carcinoma HeLa Cell Line

Year 2024, Volume: 45 Issue: 1, 15 - 19, 28.03.2024

Zeynep Büşra Bolat

https://doi.org/10.17776/csj.1394831

Abstract

Cervical carcinoma is a common gynecological cancer with high mortality rate among women worldwide. Caffeic acid exerts an antiproliferative effect against cervical carcinoma. Dactolisib is a dual PI3K and mTOR inhibitor that has a therapeutic potential for cervical carcinoma. This study aimed to reveal the anti-proliferative effect of combination treatment of caffeic acid and Dactolisib on cervical carcinoma HeLa cell line. Cytotoxicity of caffeic acid and Dactolisib on HeLa cell line was assessed by MTS assay. Colony formation of HeLa cells treated with caffeic acid and Dactolisib was determined by staining colonies with crystal violet and visualizing under light microscope. Dactolisib decreased cell proliferation of HeLa cells in time and dose dependent manner. 5 μM caffeic acid did not show any significant change in cell viability of HeLa cells. Combination treatment of 5 μM caffeic acid and 0.5 μM Dactolisib showed decrease in cell viability of HeLa cells when compared to Dactolisib treated cells. Combination of caffeic acid and Dactolisib decreased colony diameter of HeLa cells significantly when compared to control group. Caffeic acid and Dactolisib shows anti-proliferative effect on human cervical carcinoma HeLa cell line, so further studies should be performed to reveal the mechanism of action.

Keywords

Cervical carcinoma Dactolisib Caffeic acid Anti-proliferative effect.

Ethical Statement

Ethics Committee Approval: Not required.

Supporting Institution

Funding: This study was funded partially by Istanbul Sabahattin Zaim University BAP grant number: BAP1000-102.

Project Number

BAP1000-102

Thanks

Acknowledgements: The human cervical carcinoma HeLa cell lines was a kind gift of Prof. Aysegul Dogan at Yeditepe University.

References

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  • [5] Mirzaei S., Gholami M.H., Zabolian A., Saleki H., Farahani M.V., Hamzehlou S., et al., Caffeic acid and its derivatives as potential modulators of oncogenic molecular pathways: New hope in the fight against cancer, Pharmacol. Res., 171 (2021) 105759.
  • [6] Alam M., Ashraf G.M., Sheikh K., Khan A., Ali S., Ansari MdM., Adnan M., Pasupuleti V.R., Hassan M.I., Potential Therapeutic Implications of Caffeic Acid in Cancer Signaling: Past, Present, and Future, Front Pharmacol., 13 (2022) 845871.
  • [7] Chung T., Moon S., Chang Y., Ko J., Lee Y.C., Cho G., Kim S.H., Kim J.G., Kim C.H., Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism, FASEB J., 18 (14) (2004) 1670–81.
  • [8] Pelinson L.P., Assmann C.E., Palma T.V., Da Cruz IBM., Pillat M.M., Mânica A., et al., Antiproliferative and apoptotic effects of caffeic acid on SK-Mel-28 human melanoma cancer cells, Mol Biol Rep, 46 (2) (2019) 2085–92.
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  • [10] Kabała-Dzik A., Rzepecka-Stojko A., Kubina R., Wojtyczka R.D., Buszman E., Stojko J., Caffeic Acid Versus Caffeic Acid Phenethyl Ester in the Treatment of Breast Cancer MCF-7 Cells: Migration Rate Inhibition, Integr Cancer Ther, 17 (4) (2018) 1247–1259.
  • [11] Kleczka A., Kubina R., Dzik R., Jasik K., Stojko J., Cholewa K., Kabala-Dzik A., Caffeic Acid Phenethyl Ester (CAPE) Induced Apoptosis in Serous Ovarian Cancer OV7 Cells by Deregulation of BCL2/BAX Genes, Molecules, 25 (2020) 3514.
  • [12] Teng Y.-N., Wang C.C.N., Liao W.-C., Lan Y-H, Hung C.-C., Caffeic Acid Attenuates Multi-Drug Resistance in Cancer Cells by Inhibiting Efflux Function of Human P-Glycoprotein, Molecules, 25 (2020) 247.
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  • [19] Xie G., Wang Z., Chen Y., Zhang S., Feng L., Meng F., Yu Z., Dual blocking of PI3K and mTOR signaling by NVP-BEZ235 inhibits proliferation in cervical carcinoma cells and enhances therapeutic response, Cancer Lett., 388 (2017) 12–20.
  • [20] Hamid M.B., Serafin A.M., Akudugu J.M., Selective therapeutic benefit of X-rays and inhibitors of EGFR, PI3K/mTOR, and Bcl-2 in breast, lung, and cervical cancer cells, Eur. J. Pharmacol., 912 (2021) 174612. [21] Lando M., Holden M., Bergersen L.C., Svendsrud D.H., Stokke T., Sundfør K., Glad I. K., Kristensen G. B., Lyng H., Gene Dosage, Expression, and Ontology Analysis Identifies Driver Genes in the Carcinogenesis and Chemoradioresistance of Cervical Cancer, PLoS Genet., 5 (2009) e1000719.
  • [22] Feng T., Zheng L., Liu F., Xu X., Mao S., Wang X., Liu J., Lu Y., Zhao W., Yu X., Tang W., Growth factor progranulin promotes tumorigenesis of cervical cancer via PI3K/Akt/mTOR signaling pathway, Oncotarget, 7 (2016) 58381–58395.
  • [23] O’Reilly K.E., Rojo F., She Q.-B., Solit D., Mills G.B., Smith D., Lane H., Hofmann F., Hicklin D. J., Ludwig D. L., Baselga J., Rosen N., mTOR Inhibition Induces Upstream Receptor Tyrosine Kinase Signaling and Activates Akt, Cancer Res., 66 (3) (2006) 1500–8.
  • [24] Gil Del Alcazar C.R., Hardebeck M.C., Mukherjee B., Tomimatsu N., Gao X., Yan J., Xie X. J., Bachoo R., Li L., Habib A. A., Burma S., Inhibition of DNA Double-Strand Break Repair by the Dual PI3K/mTOR Inhibitor NVP-BEZ235 as a Strategy for Radiosensitization of Glioblastoma, Clin. Cancer Res., 20 (5) (2014) 1235–48.
  • [25] Wang P., Henning S.M., Heber D., Limitations of MTT and MTS-Based Assays for Measurement of Antiproliferative Activity of Green Tea Polyphenols, PLoS ONE, 5 (4) (2010) e10202.
  • [26] Gao Q., Feng J., Liu W., Wen C., Wu Y., Liao Q., Zou L., Sui X., Xie T., Zhang J., Hu Y., Opportunities and challenges for co-delivery nanomedicines based on combination of phytochemicals with chemotherapeutic drugs in cancer treatment, Adv. Drug Deliv. Rev., 188 (2022) 114445.
  • [27] Ialongo D., Tudino V., Arpacioglu M., Messore A., Patacchini E., Costi R., Santo R. D., Madia V. N., Synergistic Effects of Caffeine in Combination with Conventional Drugs: Perspectives of a Drug That Never Ages, Pharmaceuticals, 16 (2023) 730.

Year 2024, Volume: 45 Issue: 1, 15 - 19, 28.03.2024

Zeynep Büşra Bolat

https://doi.org/10.17776/csj.1394831

Abstract

Project Number

BAP1000-102

References

  • [1] Podwika S.E., Duska L.R, Top advances of the year: Cervical cancer, Cancer, 129 (2023) 657–63.
  • [2] Bahrami A., Hasanzadeh M., Hassanian S.M., ShahidSales S., Ghayour‐Mobarhan M., Ferns G.A., Avan A., The Potential Value of the PI3K/Akt/mTOR Signaling Pathway for Assessing Prognosis in Cervical Cancer and as a Target for Therapy, J of Cell. Biochem., 118 (2017) 4163–9.
  • [3] Brown A., Kumar S., Tchounwou P.B., Cisplatin-Based Chemotherapy of Human Cancers, J.Cancer Sci Ther, 11(4) (2020).
  • [4] Hussain Y., Islam L., Khan H., Filosa R., Aschner M., Javed S., Curcumin–cisplatin chemotherapy: A novel strategy in promoting chemotherapy efficacy and reducing side effects, Phytother. Res., 35 (12) (2021) 6514–6529.
  • [5] Mirzaei S., Gholami M.H., Zabolian A., Saleki H., Farahani M.V., Hamzehlou S., et al., Caffeic acid and its derivatives as potential modulators of oncogenic molecular pathways: New hope in the fight against cancer, Pharmacol. Res., 171 (2021) 105759.
  • [6] Alam M., Ashraf G.M., Sheikh K., Khan A., Ali S., Ansari MdM., Adnan M., Pasupuleti V.R., Hassan M.I., Potential Therapeutic Implications of Caffeic Acid in Cancer Signaling: Past, Present, and Future, Front Pharmacol., 13 (2022) 845871.
  • [7] Chung T., Moon S., Chang Y., Ko J., Lee Y.C., Cho G., Kim S.H., Kim J.G., Kim C.H., Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism, FASEB J., 18 (14) (2004) 1670–81.
  • [8] Pelinson L.P., Assmann C.E., Palma T.V., Da Cruz IBM., Pillat M.M., Mânica A., et al., Antiproliferative and apoptotic effects of caffeic acid on SK-Mel-28 human melanoma cancer cells, Mol Biol Rep, 46 (2) (2019) 2085–92.
  • [9] Sanderson J.T., Clabault H., Patton C., Lassalle-Claux G., Jean-François J., Paré A.F., Hébert M.J.G., Surette M.E., Touaibia M., Antiproliferative, antiandrogenic and cytotoxic effects of novel caffeic acid derivatives in LNCaP human androgen-dependent prostate cancer cells, Bioorg Med Chem, 21 (22) (2013) 7182–93.
  • [10] Kabała-Dzik A., Rzepecka-Stojko A., Kubina R., Wojtyczka R.D., Buszman E., Stojko J., Caffeic Acid Versus Caffeic Acid Phenethyl Ester in the Treatment of Breast Cancer MCF-7 Cells: Migration Rate Inhibition, Integr Cancer Ther, 17 (4) (2018) 1247–1259.
  • [11] Kleczka A., Kubina R., Dzik R., Jasik K., Stojko J., Cholewa K., Kabala-Dzik A., Caffeic Acid Phenethyl Ester (CAPE) Induced Apoptosis in Serous Ovarian Cancer OV7 Cells by Deregulation of BCL2/BAX Genes, Molecules, 25 (2020) 3514.
  • [12] Teng Y.-N., Wang C.C.N., Liao W.-C., Lan Y-H, Hung C.-C., Caffeic Acid Attenuates Multi-Drug Resistance in Cancer Cells by Inhibiting Efflux Function of Human P-Glycoprotein, Molecules, 25 (2020) 247.
  • [13] Pavlíková N., Caffeic Acid and Diseases—Mechanisms of Action, Int. J. Mol. Sci, 24 (1) (2022) 588.
  • [14] Koraneekit A., Limpaiboon T., Sangka A., Boonsiri P., Daduang S., Daduang J., Synergistic effects of cisplatin-caffeic acid induces apoptosis in human cervical cancer cells via the mitochondrial pathways, Oncol. Lett., 15 (5) (2018) 7397-7402.
  • [15] Polivka J., Janku F., Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway, Pharmacol. Ther., 142 (2014) 164–75.
  • [16] Zhang L., Wu J., Ling M.T., Zhao L., Zhao K.-N., The role of the PI3K/Akt/mTOR signalling pathway in human cancers induced by infection with human papillomaviruses, Mol Cancer, 14 (2015) 87.
  • [17] Lee C.M., Fuhrman C.B., Planelles V., Peltier M.R., Gaffney D.K., Soisson A.P.,Dodson M. K., Tolley H. D., Green C. L., Zempolich K. A., Phosphatidylinositol 3-Kinase Inhibition by LY294002 Radiosensitizes Human Cervical Cancer Cell Lines, Clin. Cancer Res., 12 (1) (2006) 250–6.
  • [18] Maira S.-M., Stauffer F., Brueggen J., Furet P., Schnell C., Fritsch C., et al., Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity, Mol Cancer Ther., 7 (7) (2008) 1851–63.
  • [19] Xie G., Wang Z., Chen Y., Zhang S., Feng L., Meng F., Yu Z., Dual blocking of PI3K and mTOR signaling by NVP-BEZ235 inhibits proliferation in cervical carcinoma cells and enhances therapeutic response, Cancer Lett., 388 (2017) 12–20.
  • [20] Hamid M.B., Serafin A.M., Akudugu J.M., Selective therapeutic benefit of X-rays and inhibitors of EGFR, PI3K/mTOR, and Bcl-2 in breast, lung, and cervical cancer cells, Eur. J. Pharmacol., 912 (2021) 174612. [21] Lando M., Holden M., Bergersen L.C., Svendsrud D.H., Stokke T., Sundfør K., Glad I. K., Kristensen G. B., Lyng H., Gene Dosage, Expression, and Ontology Analysis Identifies Driver Genes in the Carcinogenesis and Chemoradioresistance of Cervical Cancer, PLoS Genet., 5 (2009) e1000719.
  • [22] Feng T., Zheng L., Liu F., Xu X., Mao S., Wang X., Liu J., Lu Y., Zhao W., Yu X., Tang W., Growth factor progranulin promotes tumorigenesis of cervical cancer via PI3K/Akt/mTOR signaling pathway, Oncotarget, 7 (2016) 58381–58395.
  • [23] O’Reilly K.E., Rojo F., She Q.-B., Solit D., Mills G.B., Smith D., Lane H., Hofmann F., Hicklin D. J., Ludwig D. L., Baselga J., Rosen N., mTOR Inhibition Induces Upstream Receptor Tyrosine Kinase Signaling and Activates Akt, Cancer Res., 66 (3) (2006) 1500–8.
  • [24] Gil Del Alcazar C.R., Hardebeck M.C., Mukherjee B., Tomimatsu N., Gao X., Yan J., Xie X. J., Bachoo R., Li L., Habib A. A., Burma S., Inhibition of DNA Double-Strand Break Repair by the Dual PI3K/mTOR Inhibitor NVP-BEZ235 as a Strategy for Radiosensitization of Glioblastoma, Clin. Cancer Res., 20 (5) (2014) 1235–48.
  • [25] Wang P., Henning S.M., Heber D., Limitations of MTT and MTS-Based Assays for Measurement of Antiproliferative Activity of Green Tea Polyphenols, PLoS ONE, 5 (4) (2010) e10202.
  • [26] Gao Q., Feng J., Liu W., Wen C., Wu Y., Liao Q., Zou L., Sui X., Xie T., Zhang J., Hu Y., Opportunities and challenges for co-delivery nanomedicines based on combination of phytochemicals with chemotherapeutic drugs in cancer treatment, Adv. Drug Deliv. Rev., 188 (2022) 114445.
  • [27] Ialongo D., Tudino V., Arpacioglu M., Messore A., Patacchini E., Costi R., Santo R. D., Madia V. N., Synergistic Effects of Caffeine in Combination with Conventional Drugs: Perspectives of a Drug That Never Ages, Pharmaceuticals, 16 (2023) 730.
There are 26 citations in total.

Details

Primary Language English
Subjects Biochemistry and Cell Biology (Other)
Journal Section Natural Sciences
Authors

Zeynep Büşra Bolat 0000-0002-9216-6336

Project Number BAP1000-102
Publication Date March 28, 2024
Submission Date November 23, 2023
Acceptance Date February 27, 2024
Published in Issue Year 2024Volume: 45 Issue: 1

Cite

APA Bolat, Z. B. (2024). The Anti-proliferative Effect of Caffeic Acid and Dactolisib on Human Cervical Carcinoma HeLa Cell Line. Cumhuriyet Science Journal, 45(1), 15-19. https://doi.org/10.17776/csj.1394831
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