Evaluation of protective effect of myricetin, a bioflavonoid in dimethyl benzanthracene-induced breast cancer in female Wistar rats

J. K. Jayakumar; P. Nirmala; B.A. Praveen Kumar; Ashok P. Kumar

doi:10.4103/2278-330X.130443

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BREAST CANCER : Original Article

03 (

); 107-111

doi:

10.4103/2278-330X.130443

Evaluation of protective effect of myricetin, a bioflavonoid in dimethyl benzanthracene-induced breast cancer in female Wistar rats

J. K. Jayakumar^1,, P. Nirmala², B.A. Praveen Kumar³, Ashok P. Kumar⁴

1 Department of Pharmacology, Sri Devaraj Urs Medical College, Kolar, Karnataka, Peoples Education Society’s Institute of Medical Sciences and Research, Kuppam, Andhra Pradesh, India

2 Department of Pharmacology Peoples Education Society’s Institute of Medical Sciences and Research, Kuppam, Andhra Pradesh, India

3 Department of Community Medicine, Peoples Education Society’s Institute of Medical Sciences and Research, Kuppam, Andhra Pradesh, India

4 Department of Biochemistry, Rajah Muthiah Medical College and Hospital, Annamalai University, Chidambaram, Tamil Nadu Peoples Education Society’s Institute of Medical Sciences and Research, Kuppam, Andhra Pradesh, India

*Corresponding author: Dr. JK Jayakumar. dr_jkshapur@yahoo.co.in

Published: 2020-12-31

MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

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Abstract

Background: Breast cancer is one of the most common cancers worldwide. Alarmingly, the incidence of breast cancer is rising rapidly in India. Aim: The present research was focused to assess the role of myricetin; a bioflavonoid in 7,12-dimethylbenzanthracene (DMBA)-induced breast cancer in female Wistar rats. Materials and Methods: A total of 36 female Wistar rats (total 6 groups, n = 6 per group) 6 - 8 weeks old, weighing 150 gm were used in the study. DMBA was given at the dose of 7.5 mg/kg subcutaneously in the mammary region once a week for 4 consecutive weeks in group 2. Vincristine was given in the dose of 500 μg/kg intraperitonially every week for 4 consecutive weeks in group 3. Myricetin was given orally in a dose of 50, 100, and 200 mg/kg in group 4, 5, and 6 respectively. The statistical significance of the data was determined using one way analysis of variance and Duncan’s multiple range test. Results: The result showed that myricetin increased the antioxidant levels in plasma, erythrocyte lysate, and breast tissue and was effective in preventing the oxidative damage induced by the carcinogen DMBA. Myricetin 50, 100, and 200 mg/kg/oral for 120 days treated animal resulted comparable results to that of standard vincristine and control groups. Conclusions: Myricetin was found to be either equieffective or more effective than vincristine in all the parameters studied. Myricetin proved the capacity of flavonols to act as antioxidant in cells represents a potential treatment in the field of oncology.

Keywords

Acknowledgment

My sincere thanks to Dr. Vanitha Samuel, Dr. Swadhin Ranjan Behera, Dr. Uday Kumar.

References

Reddy NS, Nirmala P, Chidambaram N, Kumar PA. Quercetin in dimethyl benzanthracene induced breast cancer in rats. Am J Pharmacol Toxicol 2012;7:68-72.
Notani PN. Global variation in cancer incidence and mortality. Curr Sci 2001;81:465-74.
Sariego J. Breast cancer in the young patient. Am Surg 2010;76:1397-400.
Miyata M, Furukawa M, Takahashi K, Gonzalez FJ, Yamazoe Y. Mechanism of 7,12-Dimethylbenz [a] anthracene-induced immunotoxicity: Role of metabolic activation at the target organ. Jpn J Pharmacol 2001;86:302-9.
Yang SK, Dower WV. Metabolic pathways of 7,12-dimethylbenz [a] anthracene in hepatic microsomes. Proc Natl Acad Sci U S A 1975;72:2601-5.
Garcia-Segura LM, Bojda-Diolez F, Lenoir V, Naftolin F, Kerdelhue B. Estrogen-like effects of the mammary carcinogen 7,12-dimethylbenz (alpha) anthracene upon hypothalamic neuronal membranes. Brain Res Bull 1992;28:625-8.
Erdman JW Jr, Balentine D, Arab L, Beecher G, Dwyer JT, Folts J, et al. Flavonoids and heart: Proceedings of the ILSI North America Flavonoids Workshop, May 31-June, 2006, Washington, DC. J Nutr 2007;137:718-37S.
Egert S, Wolffram S, Bosy-Westphal A, Boesch-Saadatmandi C, Wagner AE, Frank J, et al. Daily quercetin supplementation dose dependently increases plasma quercetin concentrations in healthy humans. J Nutr 2008;138:1615-21.
Filipe P, Haigle J, Silva JN, Freitas J, Fernandes A, Mazière JC, et al. Anti-and pro-oxidant effects of quercetin in copper-induced low density lipoprotein oxidation Quercetin as an effective antioxidant against pro-oxidant effects of urate. Eur J Biochem 2004;271:1991-9.
Marozzi FJ Jr, Kocialski AB, Malone MH. Studies on the antihistaminic effects of thymoquinone, thymohydroquinone and quercetin. Arzneimittelforschung 1970;20:1574-7.
Janisch KM, Williamson G, Needs P, Plumb GW. Properties of quercetin conjugates: modulation of LDL oxidation and binding to human serum albumin. Free Radic Res 2004;38:877-84.
Wadsworth TL, Koop DR. Effects of the wine polyphenolics quercetin and resveratrol on pro-inflammatory cytokine expression in RAW 264.7 macrophages. Biochem Pharmacol 1999;57:941-9.
Chan MM, Mattiacci JA, Hwang HS, Shah A, Fong D. Synergy between ethanol and grape polyphenols, quercetin and resveratrol, in the inhibition of the inducible nitric oxide synthase pathway. Biochem Pharmacol 2000;60:1539-48.
Glass GA, Gershon H, Gershon D. The effect of donor and cell age on several characteristics of rat erythrocytes. Exp Hematol 1983;11:987-95.
Masotti L, Casali E, Galeotti T. Lipid peroxidation in tumour cells. Free Radic Biol Med 1988;4:377-86.
Ohkawa H, Onishi N, Yagi K. Assay for lipid peroxides in animal tissue by thiobarbituric acid reaction. Anal Biochem 1979;95:351-8.
Kakkar P, Das B, Viswanathan PN. A modified spectophotometric assay of superoxide dismutase. Indian J Biochem Biophys 1984;21:130-2.
Navarro J, Obsrador E, Carretero J, Petschen I, Avino J, Perez P, et al. Changes in glutathione status and the antioxidant system in blood and in cancer cells associated with tumour growth in vivo. Free Radic Biol Med 1999;26:410-8.
Das U. A radical approach to cancer. Med Sci Monit 2002;8:RA79-92.
Elucheri S, Overley TD, Qi W, Eisenstein RS, Jackson Roberts L, Van Remmen H, et al. CuZn SOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life. Oncogene 2005;24:367-80.
Sun Y. Free radicals antioxidant enzymes and carcinogenesis. Free Radic Biol Med 1990;8:583-99.
Oberley LW, Oberley TD. Role of antioxidant enzymes in the cancer phenotype. In: Clerch LB, Massaro D, editors. Oxygen, Gene Expression and Cellular Function. Washington: Marcel Dekker; 1997. p. 279-308.
Laxmi A, Subramanian S. Chemotherapeutic effect of tangeretin, a polymethoxylated flavone studied in 7, 12-dimethylbenz (a) anthracene induced mammary carcinoma in experimental rats. Biochimie 2013.
Skrajnowska D, Bobrowska-Korczak B, Tokarz A, Bialek S, Jezierska E, Makowska J. Copper and resveratrol attenuates serum catalase, glutathione peroxidase, and element values in rats with DMBA-induced mammary carcinogenesis. Biol Trace Elem Res 2013;156:271-8.
de Assis S, Wang M, Jin L, Bouker KB, Hilakivi-Clarke LA. Exposure to excess estradiol or leptin during pregnancy increases mammary cancer risk and prevents parity-induced protective genomic changes in rats. Cancer Prev Res (Phila) 2013;6:1194-211.
Nandakumar N, Rengarajan T, Balamurugan A, Balasubramanian M. Modulating effects of hesperidin on key carbohydrate-metabolizing enzymes, lipid profile, and membrane-bound adenosine triphosphatases against 7,12-dimethylbenz (a) anthracene-induced breast carcinogenesis. Hum Exp Toxicol 2013.
Yang SH, Suh JH, Lee MG, Kim SH. Pharmacokinetic drug interactions between ondansetron and tamoxifen in female Sprague-Dawley rats with DMBA-induced mammary tumor. Anticancer Res 2013;33:521-8.

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[1] Reddy NS, Nirmala P, Chidambaram N, Kumar PA. Quercetin in dimethyl benzanthracene induced breast cancer in rats. Am J Pharmacol Toxicol 2012;7:68-72.

[2] Notani PN. Global variation in cancer incidence and mortality. Curr Sci 2001;81:465-74.

[3] Sariego J. Breast cancer in the young patient. Am Surg 2010;76:1397-400.

[4] Miyata M, Furukawa M, Takahashi K, Gonzalez FJ, Yamazoe Y. Mechanism of 7,12-Dimethylbenz [a] anthracene-induced immunotoxicity: Role of metabolic activation at the target organ. Jpn J Pharmacol 2001;86:302-9.

[5] Yang SK, Dower WV. Metabolic pathways of 7,12-dimethylbenz [a] anthracene in hepatic microsomes. Proc Natl Acad Sci U S A 1975;72:2601-5.

[6] Garcia-Segura LM, Bojda-Diolez F, Lenoir V, Naftolin F, Kerdelhue B. Estrogen-like effects of the mammary carcinogen 7,12-dimethylbenz (alpha) anthracene upon hypothalamic neuronal membranes. Brain Res Bull 1992;28:625-8.

[7] Erdman JW Jr, Balentine D, Arab L, Beecher G, Dwyer JT, Folts J, et al. Flavonoids and heart: Proceedings of the ILSI North America Flavonoids Workshop, May 31-June, 2006, Washington, DC. J Nutr 2007;137:718-37S.

[8] Egert S, Wolffram S, Bosy-Westphal A, Boesch-Saadatmandi C, Wagner AE, Frank J, et al. Daily quercetin supplementation dose dependently increases plasma quercetin concentrations in healthy humans. J Nutr 2008;138:1615-21.

[9] Filipe P, Haigle J, Silva JN, Freitas J, Fernandes A, Mazière JC, et al. Anti-and pro-oxidant effects of quercetin in copper-induced low density lipoprotein oxidation Quercetin as an effective antioxidant against pro-oxidant effects of urate. Eur J Biochem 2004;271:1991-9.

[10] Marozzi FJ Jr, Kocialski AB, Malone MH. Studies on the antihistaminic effects of thymoquinone, thymohydroquinone and quercetin. Arzneimittelforschung 1970;20:1574-7.

[11] Janisch KM, Williamson G, Needs P, Plumb GW. Properties of quercetin conjugates: modulation of LDL oxidation and binding to human serum albumin. Free Radic Res 2004;38:877-84.

[12] Wadsworth TL, Koop DR. Effects of the wine polyphenolics quercetin and resveratrol on pro-inflammatory cytokine expression in RAW 264.7 macrophages. Biochem Pharmacol 1999;57:941-9.

[13] Chan MM, Mattiacci JA, Hwang HS, Shah A, Fong D. Synergy between ethanol and grape polyphenols, quercetin and resveratrol, in the inhibition of the inducible nitric oxide synthase pathway. Biochem Pharmacol 2000;60:1539-48.

[14] Glass GA, Gershon H, Gershon D. The effect of donor and cell age on several characteristics of rat erythrocytes. Exp Hematol 1983;11:987-95.

[15] Masotti L, Casali E, Galeotti T. Lipid peroxidation in tumour cells. Free Radic Biol Med 1988;4:377-86.

[16] Ohkawa H, Onishi N, Yagi K. Assay for lipid peroxides in animal tissue by thiobarbituric acid reaction. Anal Biochem 1979;95:351-8.

[17] Kakkar P, Das B, Viswanathan PN. A modified spectophotometric assay of superoxide dismutase. Indian J Biochem Biophys 1984;21:130-2.

[18] Navarro J, Obsrador E, Carretero J, Petschen I, Avino J, Perez P, et al. Changes in glutathione status and the antioxidant system in blood and in cancer cells associated with tumour growth in vivo. Free Radic Biol Med 1999;26:410-8.

[19] Das U. A radical approach to cancer. Med Sci Monit 2002;8:RA79-92.

[20] Elucheri S, Overley TD, Qi W, Eisenstein RS, Jackson Roberts L, Van Remmen H, et al. CuZn SOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life. Oncogene 2005;24:367-80.

[21] Sun Y. Free radicals antioxidant enzymes and carcinogenesis. Free Radic Biol Med 1990;8:583-99.

[22] Oberley LW, Oberley TD. Role of antioxidant enzymes in the cancer phenotype. In: Clerch LB, Massaro D, editors. Oxygen, Gene Expression and Cellular Function. Washington: Marcel Dekker; 1997. p. 279-308.

[23] Laxmi A, Subramanian S. Chemotherapeutic effect of tangeretin, a polymethoxylated flavone studied in 7, 12-dimethylbenz (a) anthracene induced mammary carcinoma in experimental rats. Biochimie 2013.

[24] Skrajnowska D, Bobrowska-Korczak B, Tokarz A, Bialek S, Jezierska E, Makowska J. Copper and resveratrol attenuates serum catalase, glutathione peroxidase, and element values in rats with DMBA-induced mammary carcinogenesis. Biol Trace Elem Res 2013;156:271-8.

[25] de Assis S, Wang M, Jin L, Bouker KB, Hilakivi-Clarke LA. Exposure to excess estradiol or leptin during pregnancy increases mammary cancer risk and prevents parity-induced protective genomic changes in rats. Cancer Prev Res (Phila) 2013;6:1194-211.

[26] Nandakumar N, Rengarajan T, Balamurugan A, Balasubramanian M. Modulating effects of hesperidin on key carbohydrate-metabolizing enzymes, lipid profile, and membrane-bound adenosine triphosphatases against 7,12-dimethylbenz (a) anthracene-induced breast carcinogenesis. Hum Exp Toxicol 2013.

[27] Yang SH, Suh JH, Lee MG, Kim SH. Pharmacokinetic drug interactions between ondansetron and tamoxifen in female Sprague-Dawley rats with DMBA-induced mammary tumor. Anticancer Res 2013;33:521-8.

Evaluation of protective effect of myricetin, a bioflavonoid in dimethyl benzanthracene-induced breast cancer in female Wistar rats

Abstract

Abstract

Keywords

Acknowledgment

References

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