α-Mangosteen as An Oxidative Inhibitor in Hepatocellular Carcinoma

Harliansyah Harliansyah, Nunung Ainur Rahmah, Kuslestari Kuslestari

Abstract


Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the second leading cause of cancer mortality worldwide. Many strategies to discover molecular-based therapy are currently being implemented to overcome the resistance in HCC treatment. Cancer research is more targeted at molecular level of natural ingredients treatment as chemoprevention to reduce carcinogenesis risk. One of the natural compounds that serve as chemopreventive agent is mangosteen. α-Mangosteen, a xanthone commonly found in the fruit hull of Garcinia mangostana Linn, possess as an antioxidant. This study aims to determine the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and protein carbonyl (PC) as the biomarkers of oxidative stress on untreated HepG2 cells compared to α-mangosteen-treated HepG2 cells. The results indicated that α-mangosteen has a cytotoxic effect on HepG2 cells with IC50=242.58 μg/mL and reduced ROS level 23.15±4.29% at 200 μg/mL. The MDA level of HepG2 cells was not significantly higher than on WRL-68 by 7.6%, 17.93%, 28.8%, 35.32%, and 61.95% at 100, 200, 500, 800, and 1000 μg/mL respectively. α-Mangosteen at 100 and 200 μg/mL reduced protein carbonyl by 76.24 and 79.84% in HepG2 cells line while compared to normal liver cells line (WRL-68) significantly (P<0.05). In conclusion, α-mangosteen reduced levels of ROS, MDA and PC. Therefore, α-mangosteen is a potential anti-cancer agent through oxidative stress inhibition.


Keyword: free radical, HepG2 cells, α-mangosteen, oxidative stress.


Full Text:

PDF

References


Adenina, S., Louisa, M., Soetikno, V., Arozal, W. and Wanandi, S.I., 2020, The Effect of Alpha Mangostin on Epithelial-Mesenchymal Transition on Human Hepatocellular Carcinoma HepG2 Cells Surviving Sorafenib via TGF-β/Smad Pathways, Advance Pharmaceutical Bulletin, 10(4), 648–655. CrossRef

Baek, J.Y., Jung, K., Kim, Y.M., Kim, H.Y., Kang, K.S. and Chin, Y.W., 2021, Protective Effect of γ-mangostin Isolated from the Peel of Garcinia mangostana against Glutamate-Induced Cytotoxicity in HT22 Hippocampal Neuronal Cells, Biomolecules, 11(2), 170. CrossRef

Barrera, G., 2012, Oxidative stress and lipid peroxidation products in cancer progression and therapy, International Scholarly Research Notices Oncology, 2012, 137289. CrossRef

Bose, S., Banerjee, S., Mondal, A., Chakraborty, U., Pumarol, J., Croley, C.R. and Bishayee, A., 2020, Targeting the JAK/STAT Signaling Pathway Using Phytocompounds for Cancer Prevention and Therapy, Cells, 9(6), 1451. CrossRef

Cazzaniga, M. and Bonanni, B., 2012, Breast Cancer Chemoprevention: Old and New Approaches, Journal of Biomedicine and Biotechnology, 2012, 985620. CrossRef

Chienwichai, P., Reamtong, O., Boonyuen, U., Trairak Pisitkun, T., Somparn, P., Tharnpoophasiam, P., Worakhunpiset, S. and Topanurak, S., 2019, Hepatic protein Carbonylation profiles induced by lipid accumulation and oxidative stress for investigating cellular response to non-alcoholic fatty liver disease in vitro, Proteome Science, 17, 1. CrossRef

Elmund, B. and Hartrianti, P., 2020, Evaluation of mangosteen (Garcinia mangostana) antioxidant activity in clinical trials and in vivo animal studies: A systematic review, Journal of Applied Pharmaceutical Science, 10(12), 114–129. CrossRef

Gani, R.A., 2017, Hepatocellular Carcinoma (HCC) Surveillance–Comprehensive Management in Liver Cirrhosis Patients, The Indonesian Journal of Gastroenterology, Hepatology and Digestive Endoscopy, 18(3), 137–139. CrossRef

Ghouri, Y.A., Mian, I. and Rowe, J.H., 2017, Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis, Journal of carcinogenesis, 16, 1. CrossRef

He, L., He, T., Farrar, S., Ji, L., Liu, T. and Ma, X., 2017, Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species, Cellular Physiology and Biochemistry, 44(2), 532–553. CrossRef

Jasirwan, C.O.M., Hasan, I., Sulaiman, A.S., Lesmana, C.R.A., Kurniawan, J., Kalista, K.M., Nababan, S.H. and Gani, R.A., 2020, Risk factors of mortality in the patients with hepatocellular carcinoma: A multicenter study in Indonesia, Current Problems in Cancer, 44(1). CrossRef

Liguori, I., Russo, G., Curcio, F., Bulli, G., Aran, L., Della-Morte, D., Gargiulo, G., Testa, G., Cacciatore, F., Bonaduce, D. and Abete, P., 2018, Oxidative stress, aging, and diseases, Clinical Interventions Aging, 13, 757–772. CrossRef

Lykkesfeldt, J., 2007, Malondialdehyde as biomarker of oxidative damage to lipids caused by smoking, Clinica Chimica Acta, 380(1–2), 50–58. CrossRef

Selvaraj, R., Kanakarazan, S. and Kamalanathan, A., 2016, Antioxidant and anticancer potential of mangosteen fruit, garcinia mangostana against hepatocellular carcinoma (HEPG-2) cell line, World Journal of Pharmacy and Pharmaceutical Sciences, 5(2), 253–293.

Le Grazie, M., Biagini, M.R., Tarocchi, M., Polvani, S. and Galli, A., 2017, Chemotherapy for hepatocellular carcinoma: The present and the future, World Journal Hepatolology, 9(21), 907–920. CrossRef

Quan, X., Wang, Y., Ma, X., Liang, Y., Tian, W., Ma, Q., Jiang, H. and Zhao, Y., 2012, α-Mangostin induces apoptosis and suppresses differentiation of 3T3-L1 cells via inhibiting fatty acid synthase, PLoS ONE, 7(3), e33376, 1–10. CrossRef

Tan, A.C., Konczak, I., Sze, D.M. and Ramzan, I., 2011, Molecular pathways for cancer chemoprevention by dietary phytochemicals, Nutrition and cancer, 63(4), 495–505. CrossRef

Wong, C-M., Marcocci, L., Das, D., Wang, X., Luo, H., Zungu-Edmondson, M. and Suzuki, Y.J., 2013, Mechanism of protein decarbonylation, Free Radical Biology & Medicine), 65, 1126–1133.




DOI: http://dx.doi.org/10.14499/indonesianjcanchemoprev12iss2pp106-113

Copyright (c) 2021 Harliansyah Harliansyah, Nunung Ainur Rahmah, Kuslestari Kuslestari

Indexed by:

               

               

      

 

Indonesian Society for Cancer Chemoprevention