Exploring the Anticancer and Antioxidant Potential Effects of Sitagliptin: An In Vitro Study on Lung Cancer Cell Lines
DOI:
https://doi.org/10.36320/ajb/v16.i2.16101Keywords:
sitagliptin, A549 cell line, cisplatin, antioxidant.Abstract
lung cancer possesses the most significant worldwide mortality rate among all types of tumors, and the majority of current treatments exhibit a broad spectrum of adverse reactions. This requires investigating novel drugs that can inhibit the growth of cancer cells while minimizing harm to normal cells. Recent studies have demonstrated that Dipeptidyl peptidase-4 (DPP4) inhibitors can effectively suppress the growth of cancer cells in several types of malignancies, including colorectal, prostate, and kidney cancers. Hence, this study evaluated the effectiveness of sitagliptin in suppressing the proliferation of lung carcinoma cells (A549) alone as well as in conjunction with cisplatin.
A549 cells were divided into four groups: control (untreated cells), cells treated with cisplatin, cells treated with sitagliptin, and cells treated with cisplatin plus sitagliptin combination (ratio 1:1). After incubation for 72 hours, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) test was utilized to evaluate cell viability percent and concentration of 50% inhibition for cell viability (IC50) for each group. Then, A549 cells were cultured into four flasks and exposed to the IC50 concentration. The resulting cell pellets were gathered and subjected to lysis to assess the malondialdehyde (MDA) level using ELISA kits.
The vitality of A549 cells was significantly reduced by Sitagliptin therapy compared to the control (P < 0.0001). When the combination of sitagliptin and cisplatin was administered, it exhibited markedly superior anticancer effectiveness compared to their usage alone. Significantly, sitagliptin reduced MDA levels, whether used individually or in combination with cisplatin.
As a result, sitagliptin exhibited significantly anticancer and antioxidant properties against A549 cells. This suggests a possible synergistic anticancer effect with cisplatin.
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References
Al-Tariahi, K. M. J., Hameed, W. S., Abdul, D. H., & Saheb, A. M. (2015). Evaluation of CA125 as a marker in patients with lung carcinoma.
Merabishvili, V. M., Arseniev, A. I., Tarkov, S. A., Barchuk, A. A., Shcherbakov, A. M., Demin, E. V., & Merabishvili, E. N. (2018). Lung cancer morbidity and mortality. Sib J Oncol, 17(6), 15-26
Benitez Majano, S., Ellis, L., & Rachet, B. (2022). Epidemiology of Lung Cancer. In Encyclopedia of Respiratory Medicine (Second Edition) (Vol. 4, pp. 663-72).
Thandra, K. C., Barsouk, A., Saginala, K., Aluru, J. S., & Barsouk, A. (2021). Epidemiology of lung cancer. Współczesna Onkol, 25(1), 45-52.
Schabath, M. B., & Cote, M. L. (2019). Cancer progress and priorities: lung cancer. Cancer Epidemiology Biomarkers & Prevention, 28(10), 1563-1579.
Reck, M., & Rabe, K. F. (2017). Precision diagnosis and treatment for advanced non–non-small-cell lung cancer. New England Journal of Medicine, 377(9), 849-861.
Brown, A., Kumar, S., & Tchounwou, P. B. (2019). Cisplatin-Based Chemotherapy of Human Cancers. Journal of Cancer Science & Therapy, 11.
Tchounwou, P. B., Dasari, S., Noubissi, F. K., Ray, P., & Kumar, S. (2021). Advances in our understanding of the molecular mechanisms of action of Cisplatin in cancer therapy. Journal of Experimental Pharmacology, 303-328.
Coolen, N. A. et al. (2010) ‘Comparison between human fetal and adult skin’, Archives of Dermatological Research. doi: 10.1007/s00403-009-0989-8.
Dasari, S., & Tchounwou, P. B. (2014). Cisplatin in cancer therapy: molecular mechanisms of action. European Journal of Pharmacology, 740, 364-378.
Aldossary, S. A. (2019). Review on pharmacology of Cisplatin: clinical use, toxicity and mechanism of resistance of Cisplatin. Biomedicine & Pharmacotherapy Journal, 12(1), 7-15.
Almagthali, A. G., Alkhaldi, E. H., Alzahrani, A. S., Alghamdi, A. K., Alghamdi, W. Y., & Kabel, A. M. (2019). Dipeptidyl peptidase-4 inhibitors: Antidiabetic drugs with potential effects on cancer. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 13(1), 36-43.
Wilson, A. L., Moffitt, L. R., Wilson, K. L., Bilandzic, M., Wright, M. D., Gorrell, M. D., ... & Stephens, A. N. (2021). DPP4 inhibitor sitagliptin enhances lymphocyte recruitment and prolongs survival in a syngeneic ovarian cancer mouse model. Cancers, 13(3), 487.
Gilbert, M. P., & Pratley, R. E. (2020). GLP1 analogs and DPP4 inhibitors in type 2 diabetes therapy: a review of headhead clinical trials. Frontiers in Endocrinology, 11, 178.
Holst, J. J., Gasbjerg, L. S., & Rosenkilde, M. M. (2021). The role of incretins on insulin function and glucose homeostasis. Endocrinology, 162(7), bqab065.
Pro, B., & Dang, N. H. (2004). CD26/dipeptidyl peptidase IV and its role in cancer. Histology and Histopathology, 19(4), 1345-1351.
Havre, P. A., Abe, M., Urasaki, Y., Ohnuma, K., Morimoto, C., & Dang, N. H. (2008). The role of CD26/dipeptidyl peptidase IV in cancer. Frontiers in Bioscience, 13, 1634-1645.
Femia, A. P., Raimondi, L., Maglieri, G., Lodovici, M., Mannucci, E., & Caderni, G. (2013). Long‐term treatment with Sitagliptin, a dipeptidyl peptidase‐4 inhibitor, reduces colon carcinogenesis and reactive oxygen species in 1, 2‐dimethylhydrazine‐induced rats. International Journal of Cancer, 133(10), 2498-2503.
Lam, C. S. C., Cheung, A. H. K., Wong, S. K. M., Wan, T. M. H., Ng, L., Chow, A. K. M., ... & Yau, T. C. (2014). Prognostic significance of CD26 in patients with colorectal cancer. PLoS One, 9(5), e98582.
Javidroozi, M., Zucker, S., & Chen, W. T. (2012). Plasma seprase and DPP4 levels as markers of disease and prognosis in cancer. Disease Markers, 32(5), 309-320.
Boccardi, V., Marano, L., Rossetti, R. R. A., Rizzo, M. R., di Martino, N., & Paolisso, G. (2015). Serum CD26 levels in patients with gastric cancer: a novel potential diagnostic marker. BMC Cancer, 15(1), 1-6.
Amritha, C. A., Kumaravelu, P., & Chellathai, D. D. (2015). Evaluation of Anticancer Effects of DPP-4 Inhibitors in Colon Cancer- An Invitro Study. Journal of Clinical and Diagnostic Research, 9(12), FC14-FC16.
Tseng, C. H. (2017). Sitagliptin may reduce breast cancer risk in women with type 2 diabetes. Clinical Breast Cancer, 17(3), 211-218.
Tseng, C. H. (2017). Sitagliptin may reduce prostate cancer risk in male patients with type 2 diabetes. Oncotarget, 8(12), 19057.
Kabel, A. M., Atef, A., & Estfanous, R. S. (2017). Ameliorative potential of Sitagliptin and/or resveratrol on experimentally-induced clear cell renal cell carcinoma. Biomedicine & Pharmacotherapy, 97, 667-674.
Bishnoi, R., Hong, Y., Shah, C., Ali, A., Skelton IV, W. P., Huo, J., ... & Dang, L. H. (2019). Dipeptidyl peptidase 4 inhibitors as novel agents in improving survival in diabetic patients with colorectal and lung cancer: A Surveillance Epidemiology and Endpoint Research Medicare study. Cancer Medicine, 8(8), 3918-3927.
Salama, M. M., Zaghloul, R. A., Khalil, R. M., & ElShishtawy, M. M. (2022). Sitagliptin Potentiats the Antineoplastic Activity of DoxorubicinExperimentallyInduced Mammary Adenocarcinoma in Mice: Implication of Oxidative Stress, Inflammation, Angiogenesis, and Apoptosis. Scientia Pharmaceutica, 90(3).
Giard, D. J., Aaronson, S. A., Todaro, G. J., Arnstein, P., Kersey, J. H., Dosik, H., & Parks, W. P. (1973). In Vitro Cultivation of Human Tumors: Establishment of Cell Lines Derived from a Series of Solid Tumors. JNCI: Journal of the National Cancer Institute, 51(5), 1417-1423.
Van Meerloo, J., Kaspers, G. J. L., & Cloos, J. (2011). Cell sensitivity assays: the MTT assay. In Cancer cell Culture: methods and protocols (pp. 237-245).
Oiseoghaede, J. O., Oyawaluja, A. A., Sowemimo, A. A., Odukoya, O. A., & Che, C. T. (2024).antiproliferative potential of ethanol leaf extract of Motandra guineensis (Thonn.) A. DC. (Apocynaceae) against human melanoma and ovarian cancer cells. Tropical Journal of Natural Product Research, 8(3 SE-Articles), 6700-6704.
Bukowski, K., Kciuk, M., & Kontek, R. (2020). Mechanisms of multidrug resistance in cancer chemotherapy. International Journal of Molecular Sciences, 21(9), 3233.
Nakashima, T., Nagano, S., Setoguchi, T., Sasaki, H., Saitoh, Y., Maeda, S., ... & Taniguchi, N. (2019). Tranilast enhances the effect of anticancer agents in osteosarcoma. Oncology Reports, 42(1), 176-188.
Jin, X., Wei, Y., Liu, Y., Lu, X., Ding, F., Wang, J., & Yang, S. (2019). Resveratrol promotes sensitization to Doxorubicin by inhibiting epithelial‐mesenchymal transition and modulating the SIRT1/β‐catenin signaling pathway in breast cancer. Cancer Medicine, 8(3), 1246-1257.
Jung, Y., & Lippard, S. J. (2007). Direct cellular responses to platinum-induced DNA damage. Chemical Reviews, 107(5), 1387-1407.
Qi, L., Luo, Q., Zhang, Y., Jia, F., Zhao, Y., & Wang, F. (2019). Advances in toxicological research of the anticancer drug cisplatin. Chemical Research in Toxicology, 32(8), 1469-1486.
Jang, J. H., Janker, F., De Meester, I., Arni, S., Borgeaud, N., Yamada, Y., ... & Jungraithmayr, W. (2019). The CD26/DPP4 inhibitor vildagliptin suppresses lung cancer growth via macrophage-mediated NK cell activity. Carcinogenesis, 40(2), 324-334.
Varela‐Calviño, R., Rodríguez‐Quiroga, M., Dias Carvalho, P., Martins, F., Serra‐Roma, A., Vázquez‐Iglesias, L., ... & Cordero, O. J. (2021). The mechanism of sitagliptin inhibition of colorectal cancer cell lines’ metastatic functionalities. IUBMB Life, 73(5), 761-773.
Kosowska, A., Garczorz, W., Kłych-Ratuszny, A., Aghdam, M. R. F., Kimsa-Furdzik, M., Simka-Lampa, K., & Francuz, T. (2020). Sitagliptin modulates the response of ovarian cancer cells to chemotherapeutic agents. International Journal of Molecular Sciences, 21(23), 1-13.
Pethanasamy, M., Suchitra, M. R., Sivasankaran, S. M., Surya, S., Elanchezhiyan, C., & Thara, J. M. (2024). In vitro Evaluation of the Antioxidant and Anticancer Activities of Chlorogenic Acid on Human Colon Cancer (HT-29) Cells. Tropical Journal of Natural Product Research, 8(3 SE-Articles), 6582-6588.
.Klaunig, J. E. (2018). Oxidative stress and cancer. Current Pharmaceutical Design, 24(40), 4771-4778.
Hayes, J. D., DinkovaKostova, A. T., & Tew, K. D. (2020). Oxidative stress in cancer. Cancer Cell, 38(2), 167-197.
Ghosh, S. (2019). Cisplatin: The first metal-based anticancer drug. Bioorganic Chemistry, 88, 102925.
Shaloam, R. D. (2015). Preclinical Assessment of Low Doses of Cisplatin in the Management of Acute Promyelocytic Leukemia. International Journal of Cancer Research and Molecular Mechanisms, 1.
ElGamal, R. Z., Tadros, M. G., & Menze, E. T. (2023). Linagliptin counteracts rotenone’s toxicity in a non-diabetic rat model of Parkinson’s disease: Insights into the neuroprotective roles of DJ-1, SIRT-1/Nrf-2, and implications of HIF1-α. European Journal of Pharmacology, 941, 175498.
Çadirci, K., Türkez, H., & Özdemir, Ö. (2019). The in vitro cytotoxicity, genotoxicity, and oxidative damage potential of the oral dipeptidyl peptidase-4 inhibitor, linagliptin, on cultured human mononuclear blood cells. Acta Endocrinologica, 15(1), 9.
Okkay, U., & Okkay, I. F. (2022). Beneficial effects of linagliptin in a cell culture model of Parkinson’s disease. European Research Journal, 8(2), 242-246.
Marques, C., Goncalves, A., Pereira, P. M. R., Almeida, D., Martins, B., Fontes-Ribeiro, C., ... & Fernandes, R. (2019). The dipeptidyl peptidase 4 inhibitor sitagliptin improves oxidative stress and ameliorates glomerular lesions in a rat model of type 1 diabetes. Life Sciences, 234, 116738.
Majeed, S. A., Hadi, N. R., Mudhafar, A. M. Al, & Al-Janabi, H. A. (2013). Sitagliptin ameliorates the progression of atherosclerosis via downregulation of the inflammatory and oxidative pathways. SAGE Open Medicine, 1, 2050312113499912.
Alameen, R., Bairam, A., & Al-Haddad, M. (2023). Antioxidant and apoptotic activities of Sitagliptin against hepatocellular carcinoma: An in vitro study. F1000Research, 12, 962.
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