The inhibitory effects of vanillin on the growth of melanoma by reducing nuclear factor-κB activation

Pourhadi, Marjan; Ghasemi, Ahmad; Abediny, Reza; Haghjooy Javanmard, Shaghayegh; Vaseghi, Golnaz

The inhibitory effects of vanillin on the growth of melanoma by reducing nuclear factor-κB activation

Document Type : Original Article

Authors

¹ Applied Physiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

² Department of Physiology, Applied Physiology Research Center, School of Medicine, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

³ Applied Physiology Research Center, Cardiovascular Research Institute; Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Melanoma is skin cancer, and the treatments are not efficient enough. Therefore, finding new drugs seems to be an essential need. Vanillin, which is extracted from vanilla seed, has anti-cancer effects by reducing nuclear factor-κB (NF). We explored the anti-tumor effects of vanillin in the melanoma model and its possible mechanism. Materials and Methods: In the MTT assay, mice melanoma cells (B16F10) were treated with vanillin (1, 2, 3, 4, 5 μg/mL) for 24 and 48 h. In an animal model, B16F10 was subcutaneously injected into C57BL/6 mice. After the development of tumors, the mice were treated with 50 and 100 mg/kg/day of vanillin for 10 days. The tumor size and expression level of NF-κB protein were measured. Results: In the MTT assay, vanillin in all concentrations significantly decreased B16F10 cell viability after 24 h incubation. The size of melanoma tumors was reduced in both doses 50 and 100 mg/kg/day in mice. NF-κB protein expression was decreased in the 100 mg/kg/day group in comparison with the control group. Conclusion: We found that vanillin by reducing NF-κB expression may have anti-tumor effects and reduced melanoma tumor size and cell viability.

Keywords

References

1.	Rastrelli M, Tropea S, Rossi CR, Alaibac M. Melanoma: Epidemiology, risk factors, pathogenesis, diagnosis and classification. In Vivo 2014;28:1005-11.
2.	Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020;70:7-30.
3.	Singh S, Zafar A, Khan S, Naseem I. Towards therapeutic advances in melanoma management: An overview. Life Sci 2017;174:50-8.
4.	Lin J, Lin Y, Huang Z, Li X. Identification of prognostic biomarkers of cutaneous melanoma based on analysis of tumor mutation burden. Comput Math Methods Med 2020;2020:8836493.
5.	Yang Y, Guo W, Ma J, Xu P, Zhang W, Guo S, et al. Downregulated TRPV1 expression contributes to melanoma growth via the calcineurin-ATF3-p53 pathway. J Invest Dermatol 2018;138:2205-15.
6.	Pereira GJ, Tavares MT, Azevedo RA, Martins BB, Cunha MR, Bhardwaj R, et al. Capsaicin-like analogue induced selective apoptosis in A2058 melanoma cells: Design, synthesis and molecular modeling. Bioorg Med Chem 2019;27:2893-904.
7.	Wu YJ, Hsu WJ, Wu LH, Liou HP, Pangilinan CR, Tyan YC, et al. Hinokitiol reduces tumor metastasis by inhibiting heparanase via extracellular signal-regulated kinase and protein kinase B pathway. Int J Med Sci 2020;17:403-13.
8.	Zamzuri NA, Abd-Aziz S. Biovanillin from agro wastes as an alternative food flavour. J Sci Food Agric 2013;93:429-38.
9.	Guo W, Liu B, Hu G, Kan X, Li Y, Gong Q, et al. Vanillin protects the blood-milk barrier and inhibits the inflammatory response in LPS-induced mastitis in mice. Toxicol Appl Pharmacol 2019;365:9-18.
10.	Bezerra DP, Soares AK, de Sousa DP. Overview of the role of vanillin on redox status and cancer development. Oxid Med Cell Longev 2016;2016:9734816.
11.	Lirdprapamongkol K, Sakurai H, Kawasaki N, Choo MK, Saitoh Y, Aozuka Y, et al. Vanillin suppresses in vitro invasion and in vivo metastasis of mouse breast cancer cells. Eur J Pharm Sci 2005;25:57-65.
12.	Ho K, Yazan LS, Ismail N, Ismail M. Toxicology study of vanillin on rats via oral and intra-peritoneal administration. Food Chem Toxicol 2011;49:25-30.
13.	Marton A, Kúsz E, Kolozsi C, Tubak V, Zagotto G, Buzás K, et al. Vanillin analogues o-vanillin and 2,4,6-trihydroxybenzaldehyde inhibit NFκB activation and suppress growth of A375 human melanoma. Anticancer Res 2016;36:5743-50.
14.	Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther 2017;2:17023.
15.	Zubair A, Frieri M. Role of nuclear factor-κB in breast and colorectal cancer. Curr Allergy Asthma Rep 2013;13:44-9.
16.	Dana N, Vaseghi G, Haghjooy Javanmard S. Activation of PPARγ inhibits TLR4 signal transduction pathway in melanoma cancer in vitro. Adv Pharm Bull 2020;10:458-63.
17.	Huang S, DeGuzman A, Bucana CD, Fidler IJ. Nuclear factor-kappaB activity correlates with growth, angiogenesis, and metastasis of human melanoma cells in nude mice. Clin Cancer Res 2000;6:2573-81.
18.	Ueda Y, Richmond A. NF-kappaB activation in melanoma. Pigment Cell Res 2006;19:112-24.
19.	Yan X, Liu DF, Zhang XY, Liu D, Xu SY, Chen GX, et al. Vanillin protects dopaminergic neurons against inflammation-mediated cell death by inhibiting ERK1/2, P38 and the NF-κB signaling pathway. Int J Mol Sci 2017;18:389.
20.	Jensen MM, Jørgensen JT, Binderup T, Kjaer A. Tumor volume in subcutaneous mouse xenografts measured by microCT is more accurate and reproducible than determined by 18F-FDG-microPET or external caliper. BMC Med Imaging 2008;8:16.
21.	Srinual S, Chanvorachote P, Pongrakhananon V. Suppression of cancer stem-like phenotypes in NCI-H460 lung cancer cells by vanillin through an Akt-dependent pathway. Int J Oncol 2017;50:1341-51.
22.	Naz H, Tarique M, Khan P, Luqman S, Ahamad S, Islam A, et al. Evidence of vanillin binding to CAMKIV explains the anti-cancer mechanism in human hepatic carcinoma and neuroblastoma cells. Mol Cell Biochem 2018;438:35-45.
23.	Elsherbiny NM, Younis NN, Shaheen MA, Elseweidy MM. The synergistic effect between vanillin and doxorubicin in ehrlich ascites carcinoma solid tumor and MCF-7 human breast cancer cell line. Pathol Res Pract 2016;212:767-77.
24.	Ho K, Yazan LS, Ismail N, Ismail M. Apoptosis and cell cycle arrest of human colorectal cancer cell line HT-29 induced by vanillin. Cancer Epidemiol 2009;33:155-60.
25.	Park EJ, Lee YM, Oh TI, Kim BM, Lim BO, Lim JH. Vanillin suppresses cell motility by inhibiting STAT3-mediated HIF-1α mRNA expression in malignant melanoma cells. Int J Mol Sci 2017;18:532.
26.	Bassères DS, Baldwin AS. Nuclear factor-kappaB and inhibitor of kappaB kinase pathways in oncogenic initiation and progression. Oncogene 2006;25:6817-30.
27.	Labbozzetta M, Notarbartolo M, Poma P. Can NF-κB be considered a valid drug target in neoplastic diseases? Our point of view. Int J Mol Sci 2020;21:3070.
28.	Russo SM, Tepper JE, Baldwin AS Jr., Liu R, Adams J, Elliott P, et al. Enhancement of radiosensitivity by proteasome inhibition: Implications for a role of NF-kappaB. Int J Radiat Oncol Biol Phys 2001;50:183-93.
29.	Gupta SC, Sundaram C, Reuter S, Aggarwal BB. Inhibiting NF-κB activation by small molecules as a therapeutic strategy. Biochim Biophys Acta 2010;1799:775-87.
30.	Lirdprapamongkol K, Sakurai H, Suzuki S, Koizumi K, Prangsaengtong O, Viriyaroj A, et al. Vanillin enhances TRAIL-induced apoptosis in cancer cells through inhibition of NF-kappaB activation. In Vivo 2010;24:501-6.
31.	Li JM, Lee YC, Li CC, Lo HY, Chen FY, Chen YS, et al. Vanillin-ameliorated development of azoxymethane/dextran sodium sulfate-induced murine colorectal cancer: The involvement of proteasome/nuclear factor-κB/mitogen-activated protein kinase pathways. J Agric Food Chem 2018;66:5563-73.
32.	Liang JA, Wu SL, Lo HY, Hsiang CY, Ho TY. Vanillin inhibits matrix metalloproteinase-9 expression through down-regulation of nuclear factor-kappaB signaling pathway in human hepatocellular carcinoma cells. Mol Pharmacol 2009;75:151-7.

Advanced Biomedical Research