Comparison of the Effects of Oxaliplatin on Nitric Oxide Synthase Activity in Colorectal Cancer (SW480) Compared to Normal Cells (HEK293)

Subject Areas : Journal of Animal Biology

Seyed َAyoub Ahmadi ¹ , Tahereh Naji ² , Rahim Ahmadi ³

1 - Department of Pharmacy and Pharmaceutical Science, Tehran Medical Science Branch, Islamic Azad University, Tehran, Iran
2 - Department of Pharmacy and Pharmaceutical Science, Tehran Medical Science Branch, Islamic Azad University, Tehran, Iran
3 - Department of Biology, Hamedan Branch, Islamic Azad University, Hamedan, Iran

Received: 2023-05-28 Accepted : 2023-07-19 Published : 2024-02-20

Keywords: nitric oxide, Oxaliplatin, Colon cancer, HEK293, SW40,

Abstract :

Colon cancer is one of the most common tumors in the human population. There are many drugs on the market to treat different types of cancer, but their use is limited due to toxic effects and side effects, and in the last ten, experts in this field are looking for suitable alternatives to common anti-cancer drugs. This study was aimed to assess the comparison of the effects of oxaliplatin on the nitric oxide level in colorectal adenocarcinoma SW480 and non-tumor HEK293 cell lines. In this experimental study, Oxaliplatin was prepared at concentrations of 1.95, 3.90, 7.8, 15.6, 32.25, 62.5, 125, 250 and 500 μg/ml and the cytotoxic effect was investigated on HEK293 and SW480 cell lines using MTT method. Nitric oxide was measured by Grease method and Real Time PCR technique was applied to evaluate the iNOS gene expression. Finally, one-way ANOVA and t-test were used to analyze the data. The results of this study indicated that Oxaliplatin had a lethal effect on the SW480 cell line at concentrations of 7.8 to 250 μg/ml, but showed no cytotoxic effects on normal cell lines at other concentrations. Oxaliplatin at concentrations of 10, 20, and 40 μg/ml significantly increased nitric oxide production in SW480 cells compared to HEK293 cells, which served as the normal cell line. The results of Real Time PCR showed that the expression of the iNOS gene in both SW480 and HEK293 cells was not significantly different from the control group, but was higher. The results indicated that use of oxaliplatin can cause excellent therapeutic effects on cancer cell lines with minimum side effects.

References:

1. Barani R., Motalleb G., Maghsoudi H. 2016. Evaluation of iNOS Expression in Esophageal Cancer Patients. Gastrointestinal Tumors, 3:44-58 [In Persian].


2. Basaki Y., Chikahisa L., Aoyagi K., Miyadera K., Yonekura K., Hashimoto A., Okabe S., Wierzba K., Yamada Y. 2001. Gamma hydroxybutyric acid and 5-fluorouracil, metabolites of UFT, inhibit the angiogenesis induced by vascular endothelial growth factor. Angiogenesis, 4: 163-73.


3. Bleiberg H. 1998. Oxaliplatin (L.OHP): a new reality in colorectal cancer. British Journal of Cancer, 77(4):1-3.


4. Danaei N., Panahi Kokhdan E., Manzouri L., Nikseresht M. 2016. The Effect of bevacizumab and hydroalcohlic Extract of Matricaria chamomilla on cell viability and nitric oxide production of the colorectal cancer cell line (HT-293). Armaghan Journal, 20(12):1107-1118 [In Persian].


5. De Rosa M., Pace U., Rega D., Costabile V., Duraturo F., Izzo P., Delrio P. 2015. Genetics, diagnosis and management of colorectal cancer (Review). Oncology and Reproduction, 34(3):1087-1096.


6. Farghaly H.S.M., Abdel-Zaher A.O., Mostafa M.G., Kotb H.I. 2012. Comparative evaluation of the effect of tricyclic antidepressants on inducible nitric oxide synthase expression in neuropathic pain model. Nitric oxide, 27(2):88-94.


7. Fung T.C., Vuong H.E., Luna C.D., Pronovost G.N., Aleksandrova A.A., Riley N.G. 2019. Intestinal serotonin and fluoxetine exposure modulate bacterial colonization in the gut. Nature Microbiology, 4(12):2064-2073.


8. Mansoori F., Sepehri H., Delphi L. 2016. Effect of pectin substances on no release and apoptosis induction in human prostate cancer cells Ln cap. Journal of Animal Research (Iranian Journal of Biology, 29(4):480-492 [In Persian].


9. Narayanan BA., Narayanan NK., Simi B., Reddy BS. 2003. Modulation of inducible nitric oxide synthase and related proinflammatory genes by the omega-3 fatty acid docosahexaenoic acid in human colon cancer cells. Cancer Research, 63(5):972-979.


10. Oliveira G.A., Cheng RY., Ridnour L.A., Basudhar D., Somasundaram V., McVicar D.W. 2017. Inducible nitric oxide synthase in the carcinogenesis of gastrointestinal cancers. Antioxidants and Redox Signaling, 26(18):1059-1077.


11. Pistritto G., Trisciuoglio D., Ceci C., Garufi A, D'Orazi G. 2016. Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies. Aging, 8(4):603-619.


12. Raymond E., Faivre S., Woynarowski J.M., Chaney S.G. 1998. Oxaliplatin: mechanism of action and antineoplastic activity. Seminars in Oncology, 25(2 Suppl 5):4-12.


13. Shisheng T., Xingchen P., Wen P., Yinglan Z., Yuquan W. 2015. Enhancement of oxaliplatin induced cell apoptosis and tumor suppression by 3-methyladenine in colon cancer. Oncology Letters, 9(5): 2056-2062.


14. Soleimani N., Daneshmandi S., Sattari M., Pourfathollah AA. 2011. Immuno-modulatory and anti-tumor effects of cuminum cyminum essential oil. Journal of Arak University of Medical Sciences, 13(4):22-29 [In Persian].


15. Tashiro T., Kawada Y., Sakurai Y., Kidani Y. 1989. Antitumor activity of a new platinum complex, oxalato (trans-l-1,2-diaminocyclohexane) platinum (II): new experimental data. Biomed. Pharmacology and Therapeutics, 43:251-60.


16. Teixeira S.F., Azevedo R.A., Silva A.C., Braga R.C. 2016. Evaluation of cytotoxic effect of the combination of a pyridinyl carboxamide derivative and oxaliplatin on NCI-H1299 human non-small cell lung carcinoma cells. Biomedical Pharmacotherapy, 84:1019-1028.


17. Urruticoechea A., Alemany R., Balart J., Villanueva A., Viñals F., Capellá G. 2010. Recent advances in cancer therapy: an overview. Current Pharmaceutical Design, 16(1):3-10.


18. Yonesi B., Mirzaie A., Aliasgari E. 2018. Cytotoxicity and apoptotic effect of oxaliplatin on colon cancer cell line (HT29) and analysis of caspase 3 and caspase 9 gene expression using Real Time PCR method. Journal of Chemical Thermodynamics, 8(4): 364-373 [In Persian].


19. Yonekura K., Basaki Y., Chikahisa L., Okabe S., Hashimoto A., Miyadera K., Wierzba K., Yamada Y. 1999. UFT and its metabolites inhibit the angiogenesis induced by murine renal cell carcinoma, as determined by a dorsal air sac assay in mice. Clinical Cancer Research, 5: 2185–91.


20. Zeng C., Yu F., Yang Y., Cheng X.2016. Preparation and evaluation of oxaliplatin thermosensitive liposomes with rapid release and high stability. PLoS One, 11(7):158-162.


21. Zhang S., Chen H., Gerhard GS. 2010. Heme synthesis increases artemisinin-induced radical formation and cytotoxicity that can be suppressed by super oxide scavengers. Chemico-biological Interactions, 186(1):30-35.


22. Zhang N. 2015. Ceramide: Therapeutic potential in combination therapy for cancer treatment. Current Drug Metabolism, 17(1):37-51.