Home Medicine Mitigation of aflatoxin B1- and sodium arsenite-induced cytotoxicities in HUC-PC urinary bladder cells by curcumin and Khaya senegalensis
Article
Licensed
Unlicensed Requires Authentication

Mitigation of aflatoxin B1- and sodium arsenite-induced cytotoxicities in HUC-PC urinary bladder cells by curcumin and Khaya senegalensis

  • Jeremiah Olorunjuwon Olugbami , Robert Damoiseaux EMAIL logo , Oyeronke Adunni Odunola and James Kazimierz Gimzewski
Published/Copyright: April 22, 2020
Journal of Basic and Clinical Physiology and Pharmacology
From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 31 Issue 4

Abstract

Background

Concomitant exposure to environmental/occupational toxicants such as aflatoxin B1 (AFB1) and arsenic in some regions of the world has been well reported. Therefore, this calls for the assessment of the efficacy of agents such as phytochemicals, which are already known for their ethno-medicinal uses in prophylaxis/remediation. We investigated the possible cytotoxic bio-interactions between AFB1 and sodium arsenite (SA) in urinary bladder cells. We also assessed the cytoprotective effects of curcumin and the ethanol stem bark extract of Khaya senegalensis (K2S).

Methods

The cells were exposed to graded levels of AFB1, SA, curcumin, and K2S for 24, 48, and 72 h. Subsequently, using optimum toxic concentrations of AFB1 and SA, respectively, the influence of non-toxic levels of curcumin and/or K2S was tested on exposure of the cells to AFB1 and/or SA. Hoechst 33342/propidium iodide staining technique was used to determine the end-points due to cytotoxicity with changes in adenosine triphosphate (ATP) levels determined using Promega’s CellTiter-Glo luminescent assay.

Results

Co-treatment of the cells with AFB1 and SA resulted in synergy in cytotoxic effects. Cytotoxicity was reduced by 3.5- and 2.9-fold by pre-treatment of the cells with curcumin and K2S before treatment with AFB1, while post-treatment resulted in 1.1- and 2.6-fold reduction, respectively. Pre-exposure of the cells with curcumin and K2S before treatment with SA ameliorated cytotoxicity by 3.8- and 3.0-fold, but post-treatment caused a 1.2- and 1.3-fold reduction, respectively.

Conclusions

Pre-treatment of the cells with either curcumin or K2S exhibited cytoprotective effects by ameliorating AFB1- and SA-induced cytotoxicity with inferred tendencies to prevent carcinogenesis.

Keywords: aflatoxin B1; curcumin; cytotoxicity; HUC-PC cells; Khaya senegalensis; sodium arsenite

Acknowledgments

The following erudite scientists are duly appreciated: Drs Jian Yu Rao, Shivani Sharma, Yusheng Jin, Chintda Santiskulvong, Weibo Yu and Mr. Bryan France.We greatly appreciate Corning Inc. (Alicia Brotchie) and Promega Corp. (Heather Bartz) for providing some of the research consumables.

  1. Research funding: JOO was supported by the U.S. Department of State’s Bureau of Educational and Cultural Affairs (Foreign Fulbright Commission) through the Institute of International Education (IIE).

  2. Author contributions: All authors have accepted the responsibility for the entire content of this manuscript and approved its submission.

  3. Conflicting interests: The authors declare no conflict of interest.

References

[1] Murta-Nascimento C, Schmitz-Dräger BJ, Zeegers MP, Steineck G, Kogevinas M, Real FX, et al. Epidemiology of urinary bladder cancer: from tumor development to patient’s death. World J Urol 2007;25:285–95.10.1007/s00345-007-0168-5Search in Google Scholar

[2] Bray F, Ferley J, Soerjomataram II, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394–424.10.3322/caac.21492Search in Google Scholar

[3] Rushing BR, Selim MI. Aflatoxin B1: a review on metabolism, toxicity, occurrence in food, occupational exposure, and detoxification methods. Food Chem Toxicol 2019;124:81–100.10.1016/j.fct.2018.11.047Search in Google Scholar

[4] Liu Y, Du M, Zhang G. Proapoptotic activity of aflatoxin B1 and sterigmatocystin in HepG2 cells. Toxicol Rep 2014;1:1076–86.10.1016/j.toxrep.2014.10.016Search in Google Scholar

[5] National Research Council. Arsenic in drinking water. Washington, DC, USA: National Academy Press, 2000.Search in Google Scholar

[6] Mithofer K, Sandy MS, Smith MT, Di Monte D. Mitochondrial poisons cause depletion of reduced glutathione in isolated hepatocytes. Arch Biochem Biophys 1992;295:132–6.10.1016/0003-9861(92)90498-LSearch in Google Scholar

[7] Zhou Q, Xi S. A review on arsenic carcinogenesis: epidemiology, metabolism, genotoxicity and epigenetic changes. Regul Toxicol Pharmacol 2018;99:78–88.10.1016/j.yrtph.2018.09.010Search in Google Scholar

[8] Malik P, Mukherjee TK. Structure-function elucidation of antioxidative and prooxidative activities of the polyphenolic compound, curcumin. Chin J Biol. 2014;(396708):1–8.10.1155/2014/396708Search in Google Scholar

[9] Tuorkey MJ. Curcumin a potent cancer preventive agent: mechanisms of cancer cell killing. Interv Med Appl Sci 2014;6:139–46.10.1556/imas.6.2014.4.1Search in Google Scholar

[10] Olugbami JO, Damoiseaux R, France B, Gbadegesin MA, Stieg AZ, Sharma S, Atomic force microscopy correlates antimetastatic potentials of HepG2 cell line with its redox/energy status: Effects of curcumin and Khaya senegalensis. J Integr Med. 2017;15:214–30.10.1016/S2095-4964(17)60337-6Search in Google Scholar

[11] Abdel-Daim MM, Abdou RH. Protective effects of diallyl sulfide and curcumin separately against thallium-induced toxicity in rats. Cell J 2015;17:379–88.Search in Google Scholar

[12] Corbi G, Conti V, Davinelli S, Scapagnini G, Filippelli A, Ferrara N. Dietary phytochemicals in neuroimmunoaging: a new therapeutic possibility for humans? Front Pharmacol 2016;7:364.10.3389/fphar.2016.00364Search in Google Scholar PubMed PubMed Central

[13] Zheng J, Cheng J, Zheng S, Feng Q, Xiao X. Curcumin, a polyphenolic curcuminoid with its protective effects and molecular mechanisms in diabetes and diabetic cardiomyopathy. Front Pharmacol 2018;9:472.10.3389/fphar.2018.00472Search in Google Scholar

[14] Adesida GA, Adesogan EK, Okorie DA, Taylor DA, Styles BT. The limonoid chemistry of the genus Khaya (Meliaceae). Phytochemistry 1971;10:1845–53.10.1016/S0031-9422(00)86448-1Search in Google Scholar

[15] Nwosu C, Hassan S, Abubakar M, Ebbo AA. Anti-diarrhoeal and toxicological studies of leaf extract of Khaya senegalensis. J Pharmacol Toxicol 2012;7:1–10.10.3923/jpt.2012.1.10Search in Google Scholar

[16] Kolawole O, Kolawole S, Ayankunle A, Olaniran A. Anti-hyperglycemic effect of Khaya senegalensis stem bark aqueous extract in Wistar rats. Eur J Med Chem 2012;2:66–73.10.9734/EJMP/2012/934Search in Google Scholar

[17] Marius L, Rakiatou T, Noufou O, Kini F. In vitro antioxidant activity and phenolic contents of different fractions of ethanolic extract from Khaya senegalensis A. Juss. (Meliaceae) stem barks. Afr J Pharm Pharmacol 2016;10:501–7.10.5897/AJPP2016.4564Search in Google Scholar

[18] Olmo L, da Silva M, Fo E, Vieira P, Fernandes JB, Marsaioli JB, et al. Rearranged limonoids from Khaya senegalensis. Phytochemistry 1996;42:831–7.10.1016/0031-9422(95)00093-3Search in Google Scholar

[19] Kubmarawa D, Khan M, Punah A, Hassan M. Phytochemical screening and antimicrobial efficacy of extracts from Khaya senegalensis against human pathogenic bacteria. Afr J Biotechnol 2008;7:23–5.Search in Google Scholar

[20] Yuan C, Zhang Y, Tang G, Di Y, Cao M, Wang X, et al. Khayseneganins AH, limonoids from Khaya senegalensis. J Nat Prod 2013;76:327–33.10.1021/np3006919Search in Google Scholar PubMed

[21] Aguoru C, Bashayi C, Ogbonna I. Phytochemical profile of stem bark extracts of Khaya senegalensis by gas chromatography-mass spectrometry (GC-MS) analysis. J Pharmacogn Phytother 2017;9:35–43.10.5897/JPP2016.0416Search in Google Scholar

[22] Olugbami JO, Damoiseaux R, France B, Onibiyo EM, Gbadegesin MA, Sharma S, et al. A comparative assessment of antiproliferative properties of resveratrol and ethanol leaf extract of Anogeissus leiocarpus (DC) Guill and Perr against HepG2 hepatocarcinoma cells. BMC Complement Altern Med 2017;17:381–92.10.1186/s12906-017-1873-2Search in Google Scholar PubMed PubMed Central

[23] Lema C, Varela-Ramirez A, Aguilera RJ. Differential nuclear staining assay for high-throughput screening to identify cytotoxic compounds. Curr Cell Biochem 2011;1:1–14.Search in Google Scholar

[24] Kawamori T, Lubet R, Steele VE, Kelloff GJ, Kaskey RB, Rao CV, et al. Chemopreventive effect of curcumin, a naturally occurring anti-inflammatory agent, during the promotion/progression stages of colon cancer. Cancer Res 1999;59:597–601.Search in Google Scholar

[25] El-Agamy DS. Comparative effects of curcumin and resveratrol on aflatoxin B1-induced liver injury in rats. Arch Toxicol 2010;84:389–96.10.1007/s00204-010-0511-2Search in Google Scholar PubMed

[26] Onu A, Saidu Y, Ladan MJ, Bilbis LS, Aliero AA, Sahabi SM. Effect of aqueous stem bark extract of Khaya senegalensis on some biochemical, haematological, and histopathological parameters of rats. J Toxicol 2013;2013:1–9.10.1155/2013/803835Search in Google Scholar

[27] Manson MM, Green JA. Effect of microsomally activated AFB1 on GGT activity in 3 rat liver cell lines. Br J Cancer 1982;45:945–52.10.1038/bjc.1982.147Search in Google Scholar

[28] Scaife JF. Aflatoxin B1: cytotoxic mode of action evaluated by mammalian cell cultures. Fed Eur Biochem Soc Lett 1971;12:143–7.10.1016/0014-5793(71)80054-6Search in Google Scholar

[29] Qureshi H, Hamid SS, Ali SS, Anwar J, Siddiqui AA, Khan NA. Cytotoxic effects of aflatoxin B1 on human brain microvascular endothelial cells of the blood-brain barrier. Med Mycol 2015;53:409–16.10.1093/mmy/myv010Search in Google Scholar PubMed

[30] Yang X-J, Lu H-Y, Li Z-Y, Bian Q, Qiu LL, Li Z, et al. Cytochrome P450 2A13 mediates aflatoxin B1-induced cytotoxicity and apoptosis in human bronchial epithelial cells. Toxicology 2012;300:138–48.10.1016/j.tox.2012.06.010Search in Google Scholar PubMed

[31] Naranmandura H, Carew MW, Xu S, Lee J, Leslie EM, Weinfeld M, et al. Comparative toxicity of arsenic metabolites in human bladder cancer EJ-1 cells. Chem Res Toxicol 2011;24:1586–96.10.1021/tx200291pSearch in Google Scholar PubMed

[32] Komissarova EV, Saha SK, Rossman TG. Dead or dying: the importance of time in cytotoxicity assays using arsenite as an example. Toxicol Appl Pharmacol 2005;202:99–107.10.1016/j.taap.2004.06.010Search in Google Scholar PubMed

[33] Graham-Evans B, Tchounwou PB, Cohly HHP. Cytotoxicity and proliferation studies with arsenic in established human cell lines: keratinocytes, melanocytes, dendritic cells, dermal fibroblasts, microvascular endothelial cells, monocytes and T-cells. Int J Mol Sci 2003;4:13–21.10.3390/i4010013Search in Google Scholar

[34] Hernández-Zavala A, Córdova E, Del Razo LM, Cebrián ME, Garrido E. Effects of arsenite on cell cycle progression in a human bladder cancer cell line. Toxicology 2005;207:49–57.10.1016/j.tox.2004.08.013Search in Google Scholar PubMed

[35] Kao Y-T, Wu C-H, Wu S-Y, Lan SH, Liu HS, Tseng YS. Arsenic treatment increase Aurora-A overexpression through E2F1 activation in bladder cells. BMC Cancer 2017;17:277.10.1186/s12885-017-3253-1Search in Google Scholar PubMed PubMed Central

[36] Barchowsky A, Dudek EJ, Treadwell MD, Wetterhahn KE. Arsenic induces oxidant stress and NF-kappa B activation in cultured aortic endothelial cells. Free Radic Biol Med 1996;21:783–90.10.1016/0891-5849(96)00174-8Search in Google Scholar

[37] Marchese S, Polo A, Ariano A, Velotto S, Costantini S, Severino L. Aflatoxin B1 and M1: biological properties and their involvement in cancer development. Toxins (Basel). 2018;10(6):214–233.10.3390/toxins10060214Search in Google Scholar

[38] Williams JH, Phillips TD, Jolly PE, Stiles JK, Jolly CM, Aggarwal D. Human aflatoxicosis in developing countries: a review of toxicology, exposure, potential health consequences, and interventions. Am J Clin Nutr 2004;80:1106–22.10.1093/ajcn/80.5.1106Search in Google Scholar

[39] Oyelami OA, Maxwell S, Adelusola KA, Aladekoma TA, Oyelese AO. Aflatoxins in the autopsy brain tissue of children in Nigeria. Mycopathologia 1995;132:35–8.10.1007/BF01138602Search in Google Scholar

[40] Hammami W, Fiori S, Al Thani R, Kali NA, Balmas V, Migheli Q, et al. Fungal and aflatoxin contamination of marketed spices. Food Control 2014;37:177–81.10.1016/j.foodcont.2013.09.027Search in Google Scholar

[41] Bbosa GS, Kitya D, Lubega A, et al. In: Guevara-Gonzalez RG, editor. Aflatoxins – recent advances and future prospects. Rijeka, Croatia: InTech Press, 2013:239–65.Search in Google Scholar

[42] Circu ML, Aw TY. Glutathione and modulation of cell apoptosis. Biochim Biophys Acta 2012;1823:1767–77.10.1016/j.bbamcr.2012.06.019Search in Google Scholar

[43] Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007;39:44–84.10.1016/j.biocel.2006.07.001Search in Google Scholar

[44] Ravindran J, Prasad S, Aggarwal BB. Curcumin and cancer cells: how many ways can curry kill tumor cells selectively? Am Assoc Pharm Sci J 2009;11:495–510.10.1208/s12248-009-9128-xSearch in Google Scholar

[45] Mehta K, Pantazis P, McQueen T, Aggarwal BB. Antiproliferative effect of curcumin (diferuloylmethane) against human breast tumor cell lines. Anticancer Drugs 1997;8:470–81.10.1097/00001813-199706000-00010Search in Google Scholar

[46] Bogdanffy MS, Valentine R. Differentiating between local cytotoxicity, mitogenesis, and genotoxicity in carcinogen risk assessments: the case of vinyl acetate. Toxicol Lett 2003;140–141:83–98.10.1016/S0378-4274(02)00504-0Search in Google Scholar

[47] Styblo M, Del Razo L, Vega L, Germolec DR, LeCluyse EL, Hamilton GA, et al. Comparative toxicity of trivalent and pentavalent inorganic and methylated arsenicals in rat and human cells. Arch Toxicol 2000;74:289–99.10.1007/s002040000134Search in Google Scholar PubMed

[48] Pi J, Yamauchi H, Kumagai Y, Sun G, Yoshida T, Aikawa H, et al. Evidence for induction of oxidative stress caused by chronic exposure of Chinese residents to arsenic contained in drinking water. Environ Health Perspect 2002;110:331–6.10.1289/ehp.02110331Search in Google Scholar PubMed PubMed Central

[49] Lynn S, Gurr J-R, Lai H-T, Jan KY. NADH oxidase activation is involved in arsenite-induced oxidative DNA damage in human vascular smooth muscle cells. Circ Res 2000;86:514–9.10.1161/01.RES.86.5.514Search in Google Scholar

Received: 2019-10-29
Accepted: 2020-01-25
Published Online: 2020-04-22

© 2020 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Editorial
  2. Anti-microbial stewardship: is it old wine in a new bottle?
  3. Reviews
  4. Tangeretin: a mechanistic review of its pharmacological and therapeutic effects
  5. Silymarin: not just another antioxidant
  6. Original Articles
  7. Melatonin ameliorates some biochemical alterations following ketoconazole administration in rats
  8. Quercetin modulates granulosa cell mRNA androgen receptor gene expression in dehydroepiandrosterone-induced polycystic ovary in Wistar rats via metabolic and hormonal pathways
  9. Comparative expression analysis of phospholipid binding protein annexina1 in nephrogenesis and kidney cancer
  10. Anthonotha macrophylla P. Beauv (Caesalpiniaceae) aqueous extract exhibits antiestrogenic effects in vitro and in vivo
  11. Urate crystals trigger B-cell receptor signal transduction and induce B-cell proliferation
  12. Effects of gabapentinoids on responses of primary cultures from rat dorsal root ganglia to inflammatory or somatosensory stimuli
  13. Anti-inflammatory potential of chia seeds oil and mucilage against adjuvant-induced arthritis in obese and non-obese rats
  14. Antiproliferative effects of combinational therapy of Lycopodium clavatum and quercetin in colon cancer cells
  15. Attenuation of oxidative stress and neurotoxicity involved in the antidepressant-like effect of the MK-801(dizocilpine) in Bacillus Calmette-Guerin-induced depression in mice
  16. 3-(Para-fluorobenzoyl)-propionic acid; a metabolite of haloperidol, reversed oestradiol valerate-induced uterine hyperplasia via modulation of oestrogen receptor signalling pathways in female Wistar rats
  17. Pharmacological evidence of Vitex thyrsiflora, Entandrophragma cylindricum, and Anonidium mannii used for the management of inflammation in Cameroon
  18. Mitigation of aflatoxin B1- and sodium arsenite-induced cytotoxicities in HUC-PC urinary bladder cells by curcumin and Khaya senegalensis
  19. Saccharum officinarum juice alters reproductive functions in male Wistar rats
  20. The effects of Pb on sperm parameters and sperm DNA fragmentation of men investigated for infertility
https://doi.org/10.1515/jbcpp-2019-0309
Keywords for this article
aflatoxin B1; curcumin; cytotoxicity; HUC-PC cells; Khaya senegalensis; sodium arsenite

Articles in the same Issue

  1. Editorial
  2. Anti-microbial stewardship: is it old wine in a new bottle?
  3. Reviews
  4. Tangeretin: a mechanistic review of its pharmacological and therapeutic effects
  5. Silymarin: not just another antioxidant
  6. Original Articles
  7. Melatonin ameliorates some biochemical alterations following ketoconazole administration in rats
  8. Quercetin modulates granulosa cell mRNA androgen receptor gene expression in dehydroepiandrosterone-induced polycystic ovary in Wistar rats via metabolic and hormonal pathways
  9. Comparative expression analysis of phospholipid binding protein annexina1 in nephrogenesis and kidney cancer
  10. Anthonotha macrophylla P. Beauv (Caesalpiniaceae) aqueous extract exhibits antiestrogenic effects in vitro and in vivo
  11. Urate crystals trigger B-cell receptor signal transduction and induce B-cell proliferation
  12. Effects of gabapentinoids on responses of primary cultures from rat dorsal root ganglia to inflammatory or somatosensory stimuli
  13. Anti-inflammatory potential of chia seeds oil and mucilage against adjuvant-induced arthritis in obese and non-obese rats
  14. Antiproliferative effects of combinational therapy of Lycopodium clavatum and quercetin in colon cancer cells
  15. Attenuation of oxidative stress and neurotoxicity involved in the antidepressant-like effect of the MK-801(dizocilpine) in Bacillus Calmette-Guerin-induced depression in mice
  16. 3-(Para-fluorobenzoyl)-propionic acid; a metabolite of haloperidol, reversed oestradiol valerate-induced uterine hyperplasia via modulation of oestrogen receptor signalling pathways in female Wistar rats
  17. Pharmacological evidence of Vitex thyrsiflora, Entandrophragma cylindricum, and Anonidium mannii used for the management of inflammation in Cameroon
  18. Mitigation of aflatoxin B1- and sodium arsenite-induced cytotoxicities in HUC-PC urinary bladder cells by curcumin and Khaya senegalensis
  19. Saccharum officinarum juice alters reproductive functions in male Wistar rats
  20. The effects of Pb on sperm parameters and sperm DNA fragmentation of men investigated for infertility
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 27.12.2025 from https://www.degruyterbrill.com/document/doi/10.1515/jbcpp-2019-0309/html
Scroll to top button