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Journal of Environmental Pathology, Toxicology and Oncology
IF: 1.625 5-Year IF: 1.63 SJR: 0.402 SNIP: 0.613 CiteScore™: 2.3

ISSN Print: 0731-8898
ISSN Online: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.2020034430
pages 247-260

Malvidin Abrogates Oxidative Stress and Inflammatory Mediators to Inhibit Solid and Ascitic Tumor Development in Mice

Kunnathur Murugesan Sakthivel
Department of Biochemistry, PSG College of Arts and Science, Civil Aerodrome Post, Coimbatore-641014, Tamil Nadu, India
Krishnamoorthy Kokilavani
Department of Biochemistry, PSG College of Arts and Science, Civil Aerodrome Post, Coimbatore-641014, Tamil Nadu, India
Chinnadurai Kathirvelan
Department of Animal Nutrition, Veterinary College and Research Institute, Tamil Nadu Veterinary and Animal Sciences University (TANUVAS), Namakkal-637002, Tamil Nadu, India
Durairaj Brindha
Department of Biochemistry, PSG College of Arts and Science, Civil Aerodrome Post, Coimbatore-641014, Tamil Nadu, India

ABSTRACT

The anticancer activity of malvidin was studied in Dalton's lymphoma ascites (DLA)-induced solid and ascitic tumor mice models. Malvidin is a natural compound belonging to the family of O-methylated anthocyanidin and plays a predominant role in regulating both short- and long-term cellular activities. Animals were injected with DLA cells (1.5 × 106 cells/animal) to induce solid and ascitic tumors. The administration of malvidin (5 mg/kg bw and 10 mg/kg bw) was carried out for 10 consecutive days from the day of tumor induction for both solid and ascitic tumors. Cyclophosphamide, CTX (25 mg/kg bw), used as the standard drug, was also administered for 10 consecutive days. Treatment with malvidin showed a significant reduction in tumor volume and elevated white blood cell (WBC) count when compared to the DLA-bearing control animals. The treatment also maintained the body weight and hemoglobin level, and decreases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) were also noted. This investigation also reported the decreased levels of cellular glutathione (GSH) in ascitic tumor groups. Malvidin reduced inflammatory mediator and cytokine levels, such as tumor necrosis factor level alpha (TNF-α) and interleukin-6 (IL-6), which serve as molecular targets for cancer prevention. A decrease in the level of reactive oxygen species (ROS), like nitric oxide (NO), was observed. Histopathological examination revealed altered morphological changes in tumor tissue and the alleviation of hepatic architecture due to DLA. Immunohistochemical analysis revealed the inhibition of iNOS. This study demonstrated that malvidin exhibited significant in vivo antitumor activity and that it was reasonably imputable to its increasing endogenous mechanism. We accent the pertinence of malvidin as a potential naturally derived drug target for tumor control.

REFERENCES

  1. Shoemaker RH, Fox JT, Juliana MM, Moeinpour FL, Grubbs CJ. Evaluation of the STAT3 inhibitor GLG-302 for the prevention of estrogen receptor-positive and negative mammary cancers. Oncol Rep. 2019;42(3):1205-13.

  2. Hartner L. Chemotherapy for oral cancer. Dent Clin. 2018;62(1):87-97.

  3. Sharma V, Gupta SK, Verma M. Dihydropyrimidine dehy- drogenase in the metabolism of the anticancer drugs. Cancer Chemother Pharmacol. 2019:84(1):1157-66.

  4. Mazza G. Compositional and functional properties of saskatoon berry and blueberry. Int J Fruit Sci. 2005;5(3): 101-20.

  5. Anna MB, Myles M, Paul K Survey of bioactive compo-nents in Western Canadian berries. Can J Physiol Pharm. 2007;85(11):1139-52.

  6. Nizamutdinova IT, Kim YM, Chung JI, Shin SC, Jeong YK, Seo HG, Lee JH, Chang KC, Kim HJ. Anthocyanins from black soybean seed coats preferentially inhibit TNF-a-mediated induction of VCAM-1 over ICAM-1 through the regulation of GATAs and IRF. J Agric Food Chem. 2009;57(16):7324-30.

  7. Routray W, Orsat V. Blueberries and their anthocyanins: factors affecting biosynthesis and properties. Compr Rev Food Sci Food Saf. 2011;10(6):303-20.

  8. Huang W, Zhu Y, Li C, Sui Z, Min W. Effect of blueberry anthocyanins malvidin and glycosides on the antioxidant properties in endothelial cells. Oxidative Med Cell Longevity. 2016. Article ID 1591803:1-10.

  9. Chai H, Wang Q, Huang L, Xie T, Fu Y. Ginsenoside Rb1 inhibits tumor necrosis factor-a-induced vascular cell adhesion molecule-1 expression in human endothelial cells. Biol Pharm Bull. 2008;31(11):2050-56.

  10. Kavitha K, Thiyagarajan P, Rathna J, Mishra R, Nagini S. Chemopreventive effects of diverse dietary phyto-chemicals against DMBA-induced hamster buccal pouch carcinogenesis via the induction of Nrf2-mediated cyto-protective antioxidant, detoxification, and DNA repair enzymes. Biochimie. 2013;95(8):1629-39.

  11. Baba AB, Kowshik J, Krishnaraj J, Sophia J, Dixit M, Nagini S. Blueberry inhibits invasion and angiogenesis in 7, 12-dimethylbenz [a] anthracene (DMBA)-induced oral squamous cell carcinogenesis in hamsters via suppression of TGF-P and NF-KB signaling pathways. J Nutr Biochem. 2016;35(1):37-47.

  12. Baba AB, Nivetha R, Chattopadhyay I, Nagini S. Blueberry and malvidin inhibit cell cycle progression and induce mitochondrial-mediated apoptosis by abrogating the JAK/STAT-3 signalling pathway. Food Chem Toxicol. 2017;109(1):534-43.

  13. Zhuang C, Guan X, Ma H, Cong H, Zhang W, Miao Z. Small molecule-drug conjugates: A novel strategy for cancer-targeted treatment. Eur J Med Chem. 2019;163(1): 883-95.

  14. Oliveira H, Wu N, Zhang Q, Wang J, Oliveira J, de Freitas V, Mateus N, He J, Fernandes I. Bioavailability studies and anticancer properties of malvidin based anthocyanins, pyranoanthocyanins and non-oxonium derivatives. Food Funct. 2016;7(5):2462-68.

  15. Wang Y, Lin J, Tian J, Si X, Jiao X, Zhang, W, Gong E, Li B. Blueberry malvidin-3-galactoside suppresses hepato-cellular carcinoma by regulating apoptosis, proliferation, and metastasis pathways in vivo and in vitro. J Agric Food Chem. 2018;67(2):625-36.

  16. Sakthivel KM, Guruvayoorappan C. Acacia ferruginea inhibits cyclophosphamide-induced immunosuppression and urotoxicity by modulating cytokines in mice. J Immunotoxicol. 2015;12(2):154-63.

  17. Thummar VR, Parasuraman S, Basu D, Raveendran R. Evaluation of in vivo antitumor activity of cleistanthin B in Swiss albino mice. J Tradit Complement Med. 2016;6(4):383-8.

  18. Kuppusamy S, Thavamani P, Megharaj M, Nirola R, Lee YB, Naidu R. Assessment of antioxidant activity, minerals, phenols and flavonoid contents of common plant/tree waste extracts. Ind Crops Prod. 2016;83(1):630-4.

  19. Bowen Forbes CS, Zhang Y, Nair MG. Anthocyanin con-tent, antioxidant, anti-inflammatory and anticancer properties of blackberry and raspberry fruits. J Food Compost Anal. 2010;23(6):554-60.

  20. Li D, Zhang Y, Liu Y, Sun R, Xia M. Purified anthocyanin supplementation reduces dyslipidemia, enhances antioxidant capacity, and prevents insulin resistance in diabetic patients. Nutr J. 2015;145(4):742-8.

  21. Thoppil RJ, Bhatia D, Barnes KF, Haznagy-Radnai E, Hohmann J, Darvesh AS, Bishayee A. Black currant antho-cyanins abrogate oxidative stress through Nrf2-mediated antioxidant mechanisms in a rat model of hepatocellular carcinoma. Curr Cancer Drug Target. 2012;12(9):1244-57.

  22. Anand K, Asthana P, Kumar A, Ambasta RK, Kumar P. Quercetin mediated reduction of angiogenic markers and chaperones in DLA-induced solid tumors. Asian Pac J Cancer Prev. 2011;12(1):2829-35.

  23. Dahiru D, Obidoa O. Evaluation of the antioxidant effects of Ziziphus mauritiana lam. leaf extracts against chronic ethanol-induced hepatotoxicity in rat liver. Afr J Tradit Complement Altern Med. 2008;5(1):39-45.

  24. Zhang M, Ning G, Shou C, Lu Y, Hong D, Zheng X. Inhibitory effect of jujuboside A on glutamate-mediated excitatory signal pathway in hippocampus. Planta Med. 2003;69(8):692-5.

  25. Liu RH, Hotchkiss JH. Potential genotoxicity of chronically elevated nitric oxide: A review. Mutat Res Genet Toxicol. 1995;339(2):73-89.

  26. Vannini F, Kashfi K, Nath N. The dual role of iNOS in cancer. Redox Biol. 2015;6(1):334-43.

  27. Wang X, Lin Y. Tumor necrosis factor and cancer, buddies or foes? Acta Pharm Sin. 2008;29(11):1275-88.

  28. Balkwill F. Tumor necrosis factor or tumor promoting factor? Cytokine Growth Factor Rev 2002;13(2):135-41.

  29. Balkwill F. Tumor necrosis factor and cancer. Nat Rev Cancer. 2009;9(5):361-71.

  30. Grivennikov SI, Karin M. Inflammatory cytokines in cancer: Tumor necrosis factor and interleukin 6 take the stage. Ann Rheu Dis. 2011;70(1):104-8.

  31. Kumari N, Dwarakanath BS, Das A, Bhatt AN. Role of interleukin-6 in cancer progression and therapeutic resistance. Tumour Biol. 2016;37(9):11553-72.

  32. Hyun JW, Chung HS. Cyanidin and malvidin from Oryza sativa cv. Heugjinjubyeo mediate cytotoxicity against human monocytic leukemia cells by arrest of G2/M phase and induction of apoptosis. J Agric Food Chem. 2004;52(8):2213-17.

  33. Patterson SJ, Fischer JG, Dulebohn RV. DNA damage in HT-29 colon cancer cells is enhanced by high concentrations of the anthocyanin Maldivin. FASEB J. 2008; 22(1):890-910.


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