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Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

General Research Article

Kolaviron Ameliorates 7, 12-Dimethylbenzanthracene - Induced Mammary Damage

Author(s): Rabiatu B. Suleiman, Aliyu Muhammad*, Ismaila A. Umara, Mohammed A. Ibrahima, Ochuko L. Erukainure, Gilead E. Forcados and Sanusi B. Katsayal

Volume 22, Issue 1, 2022

Published on: 22 March, 2021

Page: [181 - 192] Pages: 12

DOI: 10.2174/1871520621666210322101232

Price: $65

Abstract

Background: Kolaviron (KV) is a flavonoid-rich portion obtained from Garcinia kola seeds with a number of reported pharmacological effects. However, its ameliorative effects on 7,12-Dimethylbenzanthracene (DMBA)-induced mammary damage has not been fully investigated, despite the reported use of the seeds in the treatment of inflammatory related disorders.

Objective: To evaluate the ameliorative effects of KV on DMBA-induced mammary damage in female Wistar rats.

Methods: Forty-nine (49) female Wistar rats were randomly assigned into seven groups of seven rats each. DMBA was administered orally to rats in five of the groups as a single dose of 80 mg/kg body wt while the remaining two groups received the vehicle. The rats were palpated weekly for 3 months to monitor tumor formation. After 3 months of DMBA administration, 1 ml of blood was collected to assay for estrogen receptor- α (ER-α) level. Thereafter, the vehicle (dimethyl sulfoxide) was daily administered to the negative control and positive control groups for the 14 days duration of the experiment while three groups were each given a daily oral dose of 50, 100, and 200 mg/kg body wt of KV for the duration of the experiment. The last DMBA-induced group received 10 mg/kg body wt of the standard drug tamoxifen twice a week, and the remaining DMBA-free group received 200 mg/kg body wt KV. Subsequently, the animals were humanely sacrificed, and ER-α, sialic acids, sialidase, sialyltransferase levels were assayed in blood and mammary tissues followed by histopathological examinations.

Results: Significantly higher levels of estrogen receptor-α (ER-α), formation of lobular neoplastic cells, epithelial hyperplasia, lymphocyte infiltration, and increased sialylation were detected in DMBA-induced rats. Treatment with KV at 50, 100, and 200 mg/kg body weight resulted in a significant (p<0.05) decrease in ER-α level, free serum sialic acid (21.1%), the total sialic acid level of the mammary tissue (21.57%), sialyltransferase activity (30.83%) as well as mRNA level of the sialyltransferase gene (ST3Gal1) were observed after KV interventions.

Conclusion: The findings suggest that KV could be further explored in targeting DMBA-induced mammary damage implicated in mammary carcinogenesis.

Keywords: 7, 12-Dimethylbenzanthracene, mammary neoplasia, hypersialylation, kolaviron, chemoprevention, ER-α.

Graphical Abstract
[1]
Mishra, S.; Srivastava, A.K.; Suman, S.; Kumar, V.; Shukla, Y. Circulating miRNAs revealed as surrogate molecular signatures for the early detection of breast cancer. Cancer Lett., 2015, 369(1), 67-75.
[http://dx.doi.org/10.1016/j.canlet.2015.07.045] [PMID: 26276721]
[2]
Ferlay, J.; Shin, H-R.; Bray, F.; Forman, D.; Mathers, C.; Parkin, D.M. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int. J. Cancer, 2010, 127(12), 2893-2917.
[http://dx.doi.org/10.1002/ijc.25516] [PMID: 21351269]
[3]
Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D.M.; Forman, D.; Bray, F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer, 2015, 136(5), E359-E386.
[http://dx.doi.org/10.1002/ijc.29210] [PMID: 25220842]
[4]
Muhammad, A.; Ibrahim, M.A.; Erukainure, O.L.; Malami, I.; Adamu, A. Spices with Breast cancer chemopreventive and therapeutic potentials: A functional foods based-review. Anticancer. Agents Med. Chem., 2018, 18(2), 182-194.
[http://dx.doi.org/10.2174/1871520617666170912121422] [PMID: 28901261]
[5]
Bai, L.; Zhu, W. p53: Structure, function and therapeutic applications. J. Cancer Mol., 2006, 2(4), 141-153.
[6]
Daniel, D.C. Highlight: BRCA1 and BRCA2 proteins in breast cancer. Microsc. Res. Tech., 2002, 59(1), 68-83.
[http://dx.doi.org/10.1002/jemt.10178] [PMID: 12242698]
[7]
Vajaria, B.N.; Patel, K.R.; Begum, R.; Patel, P.S. Sialylation: An avenue to target cancer cells. Pathol. Oncol. Res., 2016, 22(3), 443-447.
[http://dx.doi.org/10.1007/s12253-015-0033-6] [PMID: 26685886]
[8]
Häuselmann, I.; Borsig, L. Altered tumor-cell glycosylation promotes metastasis. Front. Oncol., 2014, 4, 28.
[http://dx.doi.org/10.3389/fonc.2014.00028] [PMID: 24592356]
[9]
Ma, X.; Dong, W.; Su, Z.; Zhao, L.; Miao, Y.; Li, N.; Zhou, H.; Jia, L. Functional roles of sialylation in breast cancer progression through miR-26a/26b targeting ST8SIA4. Cell Death Dis., 2016, 7(12)e2561
[http://dx.doi.org/10.1038/cddis.2016.427] [PMID: 28032858]
[10]
Miyagi, T.; Takahashi, K.; Hata, K.; Shiozaki, K.; Yamaguchi, K. Sialidase significance for cancer progression. Glycoconj. J., 2012, 29(8-9), 567-577.
[http://dx.doi.org/10.1007/s10719-012-9394-1] [PMID: 22644327]
[11]
Li, F.; Ding, J. Sialylation is involved in cell fate decision during development, reprogramming and cancer progression. Protein Cell, 2019, 10(8), 550-565.
[http://dx.doi.org/10.1007/s13238-018-0597-5] [PMID: 30478534]
[12]
Büll, C.; Boltje, T.J.; Wassink, M.; de Graaf, A.M.; van Delft, F.L.; den Brok, M.H.; Adema, G.J. Targeting aberrant sialylation in cancer cells using a fluorinated sialic acid analog impairs adhesion, migration, and in vivo tumor growth. Mol. Cancer Ther., 2013, 12(10), 1935-1946.
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0279] [PMID: 23974695]
[13]
Büll, C.; Stoel, M.A.; den Brok, M.H.; Adema, G.J. Sialic acids sweeten a tumor’s life. Cancer Res., 2014, 74(12), 3199-3204.
[http://dx.doi.org/10.1158/0008-5472.CAN-14-0728] [PMID: 24830719]
[14]
Shah, M.H.; Telang, S.D.; Shah, P.M.; Patel, P.S. Tissue and serum α 2-3- and α 2-6-linkage specific sialylation changes in oral carcinogenesis. Glycoconj. J., 2008, 25(3), 279-290.
[http://dx.doi.org/10.1007/s10719-007-9086-4] [PMID: 18158621]
[15]
Sreeramulu, V.; Ramana, C.V. Evaluation of serum total and lipid associated sialic acid as a tumor marker in breast malignancy. IOSR J. Pharm. Biol. Sci., 2014, 9(2), 14-17.
[http://dx.doi.org/10.9790/3008-09241417]
[16]
Sönmez, H.; Süer, S.; Güngör, Z.; Baloglu, H.; Kökoglu, E. Tissue and serum sialidase levels in breast cancer. Cancer Lett., 1999, 136(1), 75-78.
[http://dx.doi.org/10.1016/S0304-3835(98)00295-X] [PMID: 10211942]
[17]
Burchell, J.; Poulsom, R.; Hanby, A.; Whitehouse, C.; Cooper, L.; Clausen, H.; Miles, D.; Taylor-Papadimitriou, J. An α2,3 sialyltransferase (ST3Gal I) is elevated in primary breast carcinomas. Glycobiology, 1999, 9(12), 1307-1311.
[http://dx.doi.org/10.1093/glycob/9.12.1307] [PMID: 10561455]
[18]
Yeo, H.L.; Fan, T.C.; Lin, R.J.; Yu, J.C.; Liao, G.S.; Chen, E.S.; Ho, M.Y.; Lin, W.D.; Chen, K.; Chen, C.H.; Hung, J.T.; Wu, J.C.; Chang, N.C.; Chang, M.D.; Yu, J.; Yu, A.L. Sialylation of vasorin by ST3Gal1 facilitates TGF-β1-mediated tumor angiogenesis and progression. Int. J. Cancer, 2019, 144(8), 1996-2007.
[http://dx.doi.org/10.1002/ijc.31891] [PMID: 30252131]
[19]
Fan, T.C.; Yeo, H.L.; Hsu, H.M.; Yu, J.C.; Ho, M.Y.; Lin, W.D.; Chang, N.C.; Yu, J.; Yu, A.L. Reciprocal feedback regulation of ST3GAL1 and GFRA1 signaling in breast cancer cells. Cancer Lett., 2018, 434, 184-195.
[http://dx.doi.org/10.1016/j.canlet.2018.07.026] [PMID: 30040982]
[20]
Rodrigues, E.; Macauley, M.S. Hypersialylation in cancer: Modulation of inflammation and therapeutic opportunities. Cancers (Basel), 2018, 10(6), 1-19.
[http://dx.doi.org/10.3390/cancers10060207] [PMID: 29912148]
[21]
Vadodkar, A.S.; Suman, S.; Lakshmanaswamy, R.; Damodaran, C. Chemoprevention of breast cancer by dietary compounds. Anticancer. Agents Med. Chem., 2012, 12(10), 1185-1202.
[http://dx.doi.org/10.2174/187152012803833008] [PMID: 22583403]
[22]
Farombi, E.O.; Shrotriya, S.; Surh, Y.J. Kolaviron inhibits dimethyl nitrosamine-induced liver injury by suppressing COX-2 and iNOS expression via NF-kappaB and AP-1. Life Sci., 2009, 84(5-6), 149-155.
[http://dx.doi.org/10.1016/j.lfs.2008.11.012] [PMID: 19081081]
[23]
Iwu, M.M. Antihepatoxic constituents of Garcinia kola seeds. Experientia, 1985, 41(5), 699-700.
[http://dx.doi.org/10.1007/BF02007729] [PMID: 3838940]
[24]
Ayepola, O.R.; Chegou, N.N.; Brooks, N.L.; Oguntibeju, O.O. Kolaviron, a Garcinia biflavonoid complex ameliorates hyperglycemia-mediated hepatic injury in rats via suppression of inflammatory responses. BMC Complement. Altern. Med., 2013, 13, 363.
[http://dx.doi.org/10.1186/1472-6882-13-363] [PMID: 24359406]
[25]
Farombi, E.O.; Owoeye, O. Antioxidative and chemopreventive properties of Vernonia amygdalina and Garcinia biflavonoid. Int. J. Environ. Res. Public Health, 2011, 8(6), 2533-2555.
[http://dx.doi.org/10.3390/ijerph8062533] [PMID: 21776245]
[26]
Farombi, E.O.; Adedara, I.A.; Ajayi, B.O.; Ayepola, O.R.; Egbeme, E.E. Kolaviron, a natural antioxidant and anti-inflammatory phytochemical prevents dextran sulphate sodium-induced colitis in rats. Basic Clin. Pharmacol. Toxicol., 2013, 113(1), 49-55.
[http://dx.doi.org/10.1111/bcpt.12050] [PMID: 23336970]
[27]
Reddy, N.S.; Nirmala, P.; Chidambaram, N.; Kumar, P.A. Quercetin in dimethyl benzanthracene induced breast cancer in rats. Am. J. Pharmacol. Toxicol., 2012, 7(2), 68-72.
[http://dx.doi.org/10.3844/ajptsp.2012.68.72]
[28]
Sahin, K.; Tuzcu, M.; Sahin, N.; Akdemir, F.; Ozercan, I.; Bayraktar, S.; Kucuk, O. Inhibitory effects of combination of lycopene and genistein on 7,12- dimethyl benz(a)anthracene-induced breast cancer in rats. Nutr. Cancer, 2011, 63(8), 1279-1286.
[http://dx.doi.org/10.1080/01635581.2011.606955] [PMID: 21958026]
[29]
Forcados, G.E.; Sallau, A.B.; Muhammad, A.; Erukainure, O.L.; James, D.B.; Damage, A.M. Vitex doniana leaves extract ameliorates alterations associated with 7, 12-dimethyl benz [ a ] anthracene-induced mammary damage in female wistar rats. Nutr. Cancer, 2021, 73(1), 98-112.
[http://dx.doi.org/10.1080/01635581.2020.1743866] [PMID: 32223342]
[30]
Dias, M.C.; Furtado, K.S.; Rodrigues, M.A.; Barbisan, L.F.; Barbisan, L.F. Effects of Ginkgo biloba on chemically-induced mammary tumors in rats receiving tamoxifen. BMC Complement. Altern. Med., 2013, 13(93), 93.
[http://dx.doi.org/10.1186/1472-6882-13-93] [PMID: 23634930]
[31]
Baer, H.J.; Collins, L.C.; Connolly, J.L.; Colditz, G.A.; Schnitt, S.J.; Tamimi, R.M. Lobule type and subsequent breast cancer risk: results from the Nurses’ Health Studies. Cancer, 2009, 115(7), 1404-1411.
[http://dx.doi.org/10.1002/cncr.24167] [PMID: 19170235]
[32]
Costa, I.; Solanas, M.; Escrich, E. Histopathologic characterization of mammary neoplastic lesions induced with 7, 12 dimethylbenz(a)anthracene in the rat. Arch. Pathol. Lab. Med., 2002, 126, 915-927.
[http://dx.doi.org/10.5858/2002-126-0915-HCOMNL] [PMID: 12171489]
[33]
Ajayi, B.O.; Adedara, I.A.; Farombi, E.O. Benzo(a)pyrene induces oxidative stress, pro-inflammatory cytokines, expression of nuclear factor-kappa B and deregulation of wnt/beta-catenin signaling in colons of BALB/c mice. Food Chem. Toxicol., 2016, 95, 42-51.
[http://dx.doi.org/10.1016/j.fct.2016.06.019] [PMID: 27338711]
[34]
Aminoff, D. Methods for the quantitative estimation of N-acetylneuraminic acid and their application to hydrolysates of sialomucoids. Biochem. J., 1961, 81, 384-392.
[http://dx.doi.org/10.1042/bj0810384] [PMID: 13860975]
[35]
Aymard-Henry, M.; Coleman, M.T.; Dowdle, W.R.; Laver, W.G.; Schild, G.C.; Webster, R.G. Influenzavirus neuraminidase and neuraminidase-inhibition test procedures. Bull. World Health Organ., 1973, 48(2), 199-202.
[PMID: 4541685]
[36]
Kiyotani, K.; Takei, N.; Matsuo, Y. Fluorometric measurement of neuraminidase activity of influenza viruses. Hiroshima J. Med. Sci., 1984, 33(2), 287-292.
[PMID: 6480393]
[37]
Køren, V.; Thiem, J. Simple and non-radioactive method for determination of sialyltransferase activity. Biotechnol. Tech., 1997, 11(5), 323-326.
[http://dx.doi.org/10.1023/A:1018423513138]
[38]
Zingue, S. Njuh, A.N.; Tueche, A.B.; Tamsa, J.; Tchoupang, E.N.; Kakene, S.D. In Vitro Cytotoxicity and In Vivo Antimammary Tumor Effects of the Hydroethanolic Extract of Acacia seyal ( Mimosaceae ) Stem Bark. 2018, 1- 13..
[39]
Altemimi, A.; Lakhssassi, N.; Baharlouei, A.; Watson, D.G.; Lightfoot, D.A. Phytochemicals: Extraction, isolation, and identification of bioactive compounds from plant extracts. Plants (Basel), 2017, 6(4), 1-23.
[http://dx.doi.org/10.3390/plants6040042] [PMID: 28937585]
[40]
Davis, L.; Kuttan, G. Effect of Withania somnifera on DMBA induced carcinogenesis. J. Ethnopharmacol., 2001, 75(2-3), 165-168.
[http://dx.doi.org/10.1016/S0378-8741(00)00404-9] [PMID: 11297845]
[41]
Moselhy, S.S. Al mslmani, M.A. Chemopreventive effect of lycopene alone or with melatonin against the genesis of oxidative stress and mammary tumors induced by 7,12 dimethyl(a)benzanthracene in sprague dawely female rats. Mol. Cell. Biochem., 2008, 319(1-2), 175-180.
[http://dx.doi.org/10.1007/s11010-008-9890-6] [PMID: 18682897]
[42]
Rajakumar, T.; Pugalendhi, P.; Thilagavathi, S. Dose response chemopreventive potential of allyl isothiocyanate against 7,12-dimethylbenz(a)anthracene induced mammary carcinogenesis in female Sprague-Dawley rats. Chem. Biol. Interact., 2015, 231, 35-43.
[http://dx.doi.org/10.1016/j.cbi.2015.02.015] [PMID: 25744308]
[43]
Amin, A. Protective effect of green algea against 7,12-dimethylbenzanthracene (DMBA)-induced breast -cancer in rats. IJCS, 2009, 1, 12-24.
[44]
Wesierska-Gadek, J.; Kramer, M.P.; Maurer, M. Resveratrol modulates roscovitine-mediated cell cycle arrest of human MCF-7 breast cancer cells. Food Chem. Toxicol., 2008, 46(4), 1327-1333.
[http://dx.doi.org/10.1016/j.fct.2007.09.004] [PMID: 17933449]
[45]
Murphy, L.C.; Watson, P. Steroid receptors in human breast tumorigenesis and breast cancer progression. Biomed. Pharmacother., 2002, 56(2), 65-77.
[http://dx.doi.org/10.1016/S0753-3322(01)00157-3] [PMID: 12000137]
[46]
Phetnoo, N.; Werawatganon, D.; Siriviriyakul, P. Review Article Genistein Could Have A Therapeutic Potential for; Thai J, 2013, pp. 120-125.
[47]
Mireia, B.N. Phytoestrogen analogues targeting neuroinflammation. Technol. Forecast. Soc. Change, 2017, 104, 1-15.
[48]
Yu, J.; Bi, X.; Yu, B.; Chen, D. Isoflavones: Anti-inflammatory benefit and possible caveats. Nutrients, 2016, 8(6), 1-16.
[http://dx.doi.org/10.3390/nu8060361] [PMID: 27294954]
[49]
Marugame, T.; Katanoda, K. International comparisons of cumulative risk of breast and prostate cancer, from cancer incidence in five continents Vol. VIII. Jpn. J. Clin. Oncol., 2006, 36(6), 399-400.
[http://dx.doi.org/10.1093/jjco/hyl049] [PMID: 16818481]
[50]
Yue, W.; Wang, J.P.; Li, Y.; Fan, P.; Liu, G.; Zhang, N.; Conaway, M.; Wang, H.; Korach, K.S.; Bocchinfuso, W.; Santen, R. Effects of estrogen on breast cancer development: Role of estrogen receptor independent mechanisms. Int. J. Cancer, 2010, 127(8), 1748-1757.
[http://dx.doi.org/10.1002/ijc.25207] [PMID: 20104523]
[51]
Choi, J.; Psarommatis, B.; Gao, Y.R.; Zheng, Y.; Handelsman, D.J.; Simanainen, U. The role of androgens in experimental rodent mammary carcinogenesis. Breast Cancer Res., 2014, 16(6), 483.
[http://dx.doi.org/10.1186/s13058-014-0483-x] [PMID: 25928046]
[52]
Sinn, H.; Kreipe, H. A brief overview of the WHO classification of breast tumorsBreast Care 4th ed.; , 2013, 8, pp. (2)149-54;
[53]
Wibowo, A.E. Sriningsih, Wuyung, P.E.; Ranasasmita, R. The Influence of DMBA (7, 12-dimethylbenz- [ a ] anthracene) regimen in the development of mammae carcinogénesis on sprague dawley female rat. Int. J. Cancer Prev., 2010, 1(1), 60-66.
[54]
Mohammed, Z.M.A.; Going, J.J.; Edwards, J.; Elsberger, B.; Doughty, J.C.; McMillan, D.C. The relationship between components of tumour inflammatory cell infiltrate and clinicopathological factors and survival in patients with primary operable invasive ductal breast cancer. Br. J. Cancer, 2012, 107(5), 864-873.
[http://dx.doi.org/10.1038/bjc.2012.347] [PMID: 22878371]
[55]
Hartmann, L.C.; Degnim, A.C.; Santen, R.J.; Dupont, W.D.; Ghosh, K. Atypical hyperplasia of the breast--risk assessment and management options. N. Engl. J. Med., 2015, 372(1), 78-89.
[http://dx.doi.org/10.1056/NEJMsr1407164] [PMID: 25551530]
[56]
Cole, K.; Tabernero, M.; Anderson, K.S. Biologic characteristics of premalignant breast disease. Cancer Biomark., 2010, 9(1-6), 177-192.
[http://dx.doi.org/10.3233/CBM-2011-0187] [PMID: 22112476]
[57]
Shaaban, A.M.; Sloane, J.P.; West, C.R.; Foster, C.S. Breast cancer risk in usual ductal hyperplasia is defined by estrogen receptor-alpha and Ki-67 expression. Am. J. Pathol., 2002, 160(2), 597-604.
[http://dx.doi.org/10.1016/S0002-9440(10)64879-1] [PMID: 11839580]
[58]
Dykes, S.S.; Hughes, V.S.; Wiggins, J.M.; Fasanya, H.O.; Tanaka, M.; Siemann, D. Stromal cells in breast cancer as a potential therapeutic target. Oncotarget, 2018, 9(34), 23761-23779.
[http://dx.doi.org/10.18632/oncotarget.25245] [PMID: 29805773]
[59]
Miyagi, T.; Yamaguchi, K. Mammalian sialidases: physiological and pathological roles in cellular functions. Glycobiology, 2012, 22(7), 880-896.
[http://dx.doi.org/10.1093/glycob/cws057] [PMID: 22377912]
[60]
Hogan-Ryan, A.; Fennelly, J.J.; Jones, M.; Cantwell, B.; Duffy, M.J. Serum sialic acid and CEA concentrations in human breast cancer. Br. J. Cancer, 1980, 41(4), 587-592.
[http://dx.doi.org/10.1038/bjc.1980.101] [PMID: 7387856]
[61]
Zhang, Z.; Wuhrer, M.; Holst, S. Serum sialylation changes in cancer. Glycoconj. J., 2018, 35(2), 139-160.
[http://dx.doi.org/10.1007/s10719-018-9820-0] [PMID: 29680984]
[62]
Oyenihi, O.R.; Brooks, N.L.; Oguntibeju, O.O. Effects of kolaviron on hepatic oxidative stress in streptozotocin induced diabetes. BMC Complement. Altern. Med., 2015, 15, 236.
[http://dx.doi.org/10.1186/s12906-015-0760-y] [PMID: 26179065]
[63]
Ayepola, O.R.; Cerf, M.E.; Brooks, N.L.; Oguntibeju, O.O. Kolaviron, a biflavonoid complex of Garcinia kola seeds modulates apoptosis by suppressing oxidative stress and inflammation in diabetes-induced nephrotoxic rats. Phytomedicine, 2014, 21(14), 1785-1793.
[http://dx.doi.org/10.1016/j.phymed.2014.09.006] [PMID: 25481391]

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