Electron microscopy study on antitumor efficacy of rutin and cisplatin combination treatment in ascites Dalton’s lymphoma-bearing mice
DOI:
https://doi.org/10.64171/JAES.6.3.39-44Keywords:
Dalton’s lymphoma, Rutin, Cisplatin, Antitumor efficacyAbstract
Cisplatin is a recognized cancer chemotherapeutic drug and its overall therapeutic efficacy is slowed down due to formation of several adverse side-effects in the host. Rutin, a naturally occurring flavonoid has proved to have many pharmacological properties. Some drugs when used in combination against cancers have proved to be much better in improving therapeutic efficacy as well as reducing alone drug induced toxicities in the hosts. Further, rutin-cisplatin combination treatment had been reported to show antitumor activity and histoprotective property in various models. The present study was focused on to evaluate antitumor efficacy of rutin-cisplatin combination treatment in ascites Dalton’s lymphoma (DL) bearing mice particularly by electron microscopy analysis.
Results: Scanning electron microscopy (SEM) of the DL cells in combination treatment with rutin and cisplatin showed severe membrane deformities in DL cells compared to alone treatment such as fusion of cell membrane, membrane blebbing, cell shrinkage, membrane folding and loss in microvilli from the tumor cell surface which may contribute to cell death. Transmission electron microscopy (TEM) of the DL cells also showed severe changes in internal architecture of cell organelles such as mitochondrial membrane disruption, elongated mitochondria with thickened and disrupted mitochondrial cristae and formation of vacuoles in DL cells in combination treatment compared to alone treatment.
Conclusion: The results obtained from SEM and TEM study showed that rutin-cisplatin combination treatment exerts more antitumor effect on DL cells compared to their alone treatment.
References
Yang Y, Adebali O, Gang W, Selby CP, Chiou YY, Rashid N, et al. Cisplatin-DNA adduct repair of transcribed genes is controlled by two circadian programs in mouse tissues. Proc Natl Acad Sci U S A. 2018;115(21):E4777-E4785.
Weiss RB, Christian MC. New cisplatin analogues in development. Drugs. 1993;46(3):360-377.
Beg T, Siddique YH, Afzal M. Protective action of flavonoids genistein and gingerol against cisplatin toxicity in vitro. J Young Pharm. 2012;4(2):124-125.
Sahu BD, Kumar JM, Sistla R. Baicalein, a bioflavonoid, prevents cisplatin induced acute kidney injury by up-regulating antioxidant defenses and down-regulating the MAPKs and NF-κB pathways. PLoS One. 2015;10(7):1-19.
Longchar A, Prasad SB. Ascorbic acid (vitamin C)-mediated protection on mutagenic potentials of cisplatin in mice bearing ascites Dalton’s lymphoma. Res J Mutagen. 2016;6(1):1-21.
Koyuncu I, Kocyigit A, Gonel A, Arslan E, Durgun M. The protective effect of naringenin-oxime on cisplatin-induced toxicity in rats. Biochem Res Int. 2017;2017:1-9.
Tiwari SC, Husain N. Biological activities and role of flavonoids in human health-a review. Indian J Sci Res. 2017;12(2):193-196.
Kreft S, Knapp M, Kreft I. Extraction of rutin from buckwheat (Fagopyrum esculentum Moench) seeds and determination by capillary electrophoresis. J Agric Food Chem. 1997;47(11):4649-4652.
Ganeshpurkar A, Saluja AK. The pharmacological potential of rutin. Saudi Pharm J. 2016;25:149-164.
Dasari S, Njiki S, Mbemi A, Yedjou CG, Tchounwou PB. Pharmacological effects of cisplatin combination with natural products in cancer chemotherapy. Int J Mol Sci. 2022;23(3):1532.
Mellou F, Loutrari H, Stamatis H, Roussos C, Kolisis FN. Enzymatic esterification of flavonoids with unsaturated fatty acids: effect of the novel esters on vascular endothelial growth factor release from K562 cells. Process Biochem. 2006;41:2029-3204.
Kopustinskiene DM, Jakstas V, Savickas A, Bernatoniene J. Flavonoids as anticancer agents. Nutrients. 2020;12(2):457.
Janbaz KH, Saeed SA, Gilani AH. Protective effect of rutin on paracetamol and CCl4-induced hepatotoxicity in rodents. Fitoterapia. 2002;73:557-563.
Salkić A, Mujezin L, Džafić A, Kučuk ZB, Žuljević SO. The importance of rutin in nutrition. Proceedings. 2023;91(1):236.
Ramhariya R, Ganeshpurkar A, Ayachi C, Kanojia P, Bansal D, Dubey N. Ameliorative effect of rutin on gentamicin-induced nephrotoxicity in murine model. Austin J Pharmacol Ther. 2015;3(1):1066-1069.
Ansar S, AlGhosoon HT, Hamed S. Evaluation of protective effect of rutin on lead acetate-induced testicular toxicity in Wistar rats. Toxin Rev. 2016;34(4):195-199.
Gelen V, Sengul E, Gedikli S, Atila G, Uslu H, Makav M. The protective effect of rutin and quercetin on 5-FU-induced hepatotoxicity in rats. Asian Pac J Trop Biomed. 2017;7(7):647-653.
Madkour D, Ahmed M, Elkirdasy A, Orabi S, Mousa A. Rutin: chemical properties, pharmacokinetic properties and biological activities. Matrouh J Vet Med. 2024;4(1):26-34.
Satari A, Ghasemi S, Habtemariam S, Asgharian S, Lorigooini Z. Rutin: A flavonoid as an effective sensitizer for anticancer therapy; insights into multifaceted mechanisms and applicability for combination therapy. Evid Based Complement Alternat Med. 2021;2021:9913179.
Elsayed HE, Ebrahim HY, Mohyeldin MM, Siddique AB, Kamal AM, Haggag EG. Rutin as a novel c-Met inhibitory lead for the control of triple negative breast malignancies. Nutr Cancer. 2017;69(8):1256-1271.
Prasad SB, Rosangkima G, Khynriam D. Cisplatin-induced toxicological effects in relation to the endogenous tissue glutathione level in tumor-bearing mice. Asian J Exp Sci. 2006;20(1):55-68.
Kalita S. Studies on modulatory effect of vitamin C on the antitumor and toxic activities of chlorambucil in tumor-bearing mice [PhD thesis]. Shillong: North-Eastern Hill University; 2014.
Mammucari C, Rizzuto R. Signaling pathways in mitochondrial dysfunction and aging. Mech Ageing Dev. 2010;131:536-543.
Liang BC, Grootveld M. The importance of mitochondria in the tumourigenic phenotype: Gliomas as the paradigm. Int J Mol Med. 2011;27:159-171.
Prasad SB, Rosangkima G, Kharbangar A. Structural and biochemical changes in mitochondria after cisplatin treatment of Dalton's lymphoma-bearing mice. Mitochondrion. 2010;10(1):38-45.
