Cytotoxic Activity and Apoptosis Induction of Ethanolic Extract of Pericarps of Mangosteen (Garcinia mangostana Linn.) on WiDr Cells and Interaction Study of Alpha-mangosteen to IKK and VEGF Based on Molecular Docking

Annishfia Lailatur Rohmah, Fikri Amalia, Erlina Rivanti, Dyaningtyas Dewi Pamungkas Putri, Nunuk Aries Nurulita


One of the compounds found efficacious as an anti-proliferative on colon cancer is alpha-mangosteen, a xanthon compound that is abundant in pericarp of mangosteen. This study focused to evaluate anticancer activity of the ethanolic extract of pericarp of mangosteen (Garcinia mangostana Linn.) on WiDr colon cancer cells and to observe the affinity of alpha-mangosteen in inhibiting IKK and VEGF. Cytotoxic effect was tested by MTT assay and apoptosis induction was evaluated by double staining method on WiDr colon cancer cells, while interaction between alpha-mangosteen to the receptors was measured by molecular docking. The ethanolic extract was proven to have cytotoxic activity against WiDr colon cancer cells with IC50 of 25 µg/mL. In addition, the observation of apoptosis induction by double-staining method showed that apoptosis associated the cytotoxic effect of ethanolic extract of pericarp of mangosteen (EPM) on WiDr colon cancer cells. Molecular docking showed that active compounds in pericarp of mangosteen could compete with the native ligand of VEGF because the docking score of alpha-mangosteen was almost equal with native ligand. From these results we could be concluded that the cytotoxic effect of EPM to WiDr cells was mediated by cell apoptosis. This extract was potential to be developed as chemopreventive agent.

Keywords : Garcinia mangostana Linn., cytotoxic effect, apoptosis, WiDr cell, molecular docking


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Boik, J, 2001, Natural Compounds in Cancer Therapy, Oregon Medical Press.

Chairungsrilerd, N., Furukawa, K., Ohta, T., Nozoe, S. and Ohizumi, Y, 1996, Pharmacological Properties of Alpha-mangosteen, a Novel Histamine H1 Receptor Antagonist, Eur. J. Pharmacol., 314(3), 351-356. CrossRef

Fujioka, S., Sclabas, G.M., Schmidt, C., Frederick, W.A., Dong, Q.G., et al., 2003, Inhibition of Constitutive NF-kappaB Activity by Ikappa Balpha M Suppresses Tumorigenesis, Oncogene, 22(9), 1365-1370. CrossRef

Gavrieli, Y., Sherman, Y. and Ben-Sasson, S.A., 1992, Identification of Programmed Cell Ddeath In Situ Via Specific Labeling of Nuclear DNA Fragmentation, J. Cell Biol., 119(3), 493-501. Link

Gewies, A., 2003, Introduction to Apoptosis, Apo Review, 1-26

Ho, C.K., Huang, Y.L. and Chen, C.C., 2002, Garcinone E, a Xanthone Derivative, has Potent Cytotoxic Effect Against Hepatocellular Carcinoma cell Lines, Planta Med., 68(11), 975 - 979. CrossRef

Hung, S.H., Shen, K.H., Wu, C.H., Liu, C.L. and Shih, Y.W., 2009, Alpha – mangosteen Suppresses PC-3 Human Prostate Carcinoma Cell Metastasis by Inhibiting Matrix Metalloproteinase- 2/9 and Urokinase-Plasminogen Expression Through the JNK Signaling Pathway, J Agric. Food Chem., 57(4), 1291-1298. CrossRef

Levrero, M., Laurenzi, V.De.,Constanzo, A., Sabatini, S., Gong, J., Wang, J.Y.J. and Melino, G., 2000, The p53/p63/p73 Family of Transcription Factors: Overlapping and Distinct Functions, J. Cell. Sci.,113(10),1661-1670. Link

Matsumoto, K., Akao, Y., Ohguchi, K., Ito, T., Tanaka, T., Iinuma, M., et al., 2005, Xanthones Induce Cell-cycle Arrest and Apoptosis in Human Colon Cancer DLD-1 Cells, Bioorg. Med. Chem., 13(21), 6064–6069. CrossRef

Moongkarndi, P., Kosem, N., Kaslungka, S., Luanratana, O., Pongpan, N. and Neungton, N., 2004, Antiproliferation, Antioxidation and Induction of Apoptosis by Garcinia mangostana (mangosteen) on SKBR3 Human Breast Cancer Cell Line, J. Ethnopharmacol., 90(1), 161-166. Link

Nabandith, V., Suzui, M., Morioka, T., Kaneshiro, T., Kinjo, T., Matsumoto, K., et al., 2004, Inhibitory Effects of Crude alpha-mangosteen, a Xanthone Derivative, on Two Different Categories of Colon Preneoplastic Lesions Induced by 1, 2-dimethylhydrazine in The Rat, Asian Pac. J. Cancer Prev., 5(4), 433–438. Link

Nakagawa, Y., Iinuma, M., Naoe, T., Nozawa, Y. and Akao, Y., 2007, Characterized Mechanism of Alpha-mangosteen-Induced Cell Death: Caspase-Independent Apoptosis with Release of Endonuclease-G from Mitochondria and Increased miR-143 Expression in Human Colon Cancer DLD-1 Cells, Bioorg. Med. Chem., 15(16), 5620–5628. CrossRef

Renvoizé, C., Biola, A.M., Pallardy, M. and Bréard, J., 1998, Apoptosis: Identification of Dying Cells, Cell Biol. Toxicol., 14, 111-120. Link

Ribble, D., Goldstein, N.B., Norris, D.A. and Shellman, Y.G., 2005, A Simple Technique for Quantifying Apoptosis in 96-well Plates, BMC Biotechnol, 5, 12. CrossRef

Ricci, M.S. and Zong, W., 2006, Chemotherapeutic Approaches for Targetting Cell Death Pathways, Oncologist, 11(4), 342-357. CrossRef

Thompson, H.J., Strange, R. and Schedin, P.J., 1992, Apoptosis in the Genesis and Prevention of Cancer, Cancer Epidemiol. Biomarkers Prev., 1(7), 597-602. Link

Turini, M.E. and Dubois, R.N., 2002, Cyclooxygenase-2: a Therapeutic Target, Ann. Rev. Med., 53, 35-57. CrossRef

Weecharangsan, W., Opanasopit, P., Sukma.M., Ngawhirunpat, T., Sotanaphun, U., et al., 2006, Antioxidative and Neuroprotective Activities of Extracts from the Fruit Hull of Mangosteen (Garcinia mangostana Linn.), Med. Princ. Pract., 15(4), 281-287. CrossRef

Winawer, S.J., 2007, The multidisciplinary management of gastrointestinal cancer. Colorectal cancer screening, Best Pract. Res. Clin. Gastroenterol., 21(6),1031–1048. CrossRef


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