APOPTOSIS INDUCTION EFFECT OF CURCUMIN AND ITS ANALOGS PENTAGAMAVUNON-0 AND PENTAGAMAVUNON-1 ON CANCER CELL LINES
Objectives: This experiment aims to investigate the apoptosis effect of curcumin and its analogs pentagamavunon-0 (PGV-0) and PGV-1 on normal
and other cancer cell lines.
Methods: Growth inhibition effect was investigated using the MTT method. Double staining used acridine orange, 2-(4-aminodiphenyl)-6-
indolcarbamidine dihydrochloride and ethidium bromide was performed to determine morphological changes of cells. Detection of PARP, caspase-3,
PUMA and BAX using a western blot method was conducted to elucidate the apoptosis effect of the compounds.
Results: PGV-1 (2.5 Î¼M) and PGV-0 (5.0 Î¼M) could inhibit T47D-cell growth on 72 h observation, but not for curcumin. DNA staining showed PGV-1
has the strongest apoptosis induction effect on T47D-cells compared to PGV-0 and curcumin as well. Western blot analysis resulted in cleavage PARP
(83 kD) on HeLa, T47D, and MCF-7 cells treated with PGV-1 (2.5 Î¼M), PGV-0 (5.0 Î¼M). Curcumin (10.0 Î¼M) just induced apoptosis on T47D-cell and
MCF-7 cell, but not HeLa cell. Cleavage PARP resulted by apoptosis process in the cell. PGV-1 (2.5 Î¼M) had a stronger apoptosis effect compared to
PGV-0 (5.0 Î¼M) and curcumin (10.0 Î¼M) based on cleaved PARP result qualitatively. On the normal cell (NH3T3), cells that were treated with the
compounds resulted in a negative cleavage PARP. This result indicated that the compounds were part of a selectively induced cancer cell line apoptosis
Conclusion: Curcumin, PGV-0 and PGV-1 could inhibit cell growth by induce apoptosis on cancer cells but not on normal cells, which PGV-1 has
strongest apoptosis induction effect on cancer cell lines.
Keywords: Curcumin and analogs, Apoptosis, Cancer cell lines.
Elgadir MA, Salama M, Adam A. Anti-breast cancer from various natural sources - Review. Int J Pharm Pharm Sci 2015;7(2):44-7.
TÃ¸nnesen HH, Karlsen J. Studies on curcumin and curcuminoids. VI. Kinetics of curcumin degradation in aqueous solution. Z Lebensm Unters Forsch 1985;180(5):402-4.
Fig. 3: Pentagamavunon-1 (2.5 Î¼g/mL). (a) And PGV-0 (5.0 Î¼g/mL), (b) induced apoptosis on HeLa, T47D and MCF-7. On higher concentration, both compounds could not induce apoptosis on NIH3T3 (normal cell) curcumin, (c) induced apoptosis on T47D and MCF-7 but not on HeLa and NIH3T3, (d) Further investigation of PGV-1 could activate caspase-3 on T47D-cells but not on HeLa and NIH3T3, increased PUMA and BAX on MCF-7 cell but not on HeLa and NIH3T3 cell
Asian J Pharm Clin Res, Vol 10, Issue 3, 2017, 373-376
Daâ€™i et al.
Van der Good H. The chemistry and qualitatitve structure activity relationships of curcumin, in recent development in curcumin pharmacochemistry. In: Pramono S, editor. Proceedings of International Symposium on Curcumin Pharmacochemistry (15cp). Yogyakarta-Indonesia. August, 29-31; 1995.
Robinson TP, Ehler T, Hubbard RB, Bai X, Arbiser JL, Goldsmith DJ, et al. Design, synthesis and biological evaluastion of aromatic enones related to curcumin. Bioorg Med chem Lett 2003;13(1):115-7.
Adams BK, Ferstl EM, Davis MC, Herold M, Kurtkaya S, Camalier RF, et al. Synthesis and biological evaluation of novel curcumin analogs as anti-cancer and anti-angiogenesis agents. Bioorg Med Chem 2004;12(4):3871-83.
Ravindran J, Prasad S, Aggarwal BB. Curcumin and cancer cells: How many ways can curry kill tumor cells selectively? AAPS J 2009;11(13):495-510.
Meiyanto E, Daâ€™i MS, Agustina D. Antiproliferative effect of pentagamavunon-0 on breast cancer cell line T47D. J Kedokt Yarsi 2006;14(1):11-5.
Meiyanto E, Agustina D, Supardjan AM, Daâ€™i M. PGV-O induces apoptosis on T47D breast cancer cell lines through caspase-3 activation. J Kedokt Yarsi 2007;15(2):75-9.
Daâ€™i M, Supardjan AM, Meiyanto E, Jenie UA. Geometric isomers and cytotoxic effect on T47D cells of curcumin analogues PGV-0 and PGV-1. Majalah Farmasi Indones 2007;18(1):40-7.
Hermawan A, Fitriasari A, Junaedi S, Ikawati M, Haryanti S, Widayarti B, et al. PGV-0 and PGV-1 increased apoptosis induction of doxorubicin on MCF7 breast cencer cells. Pharmacon 2011;12(2):55-9.
Daâ€™i M, Supardjan AM, Jenie UA, Kawaichi M, Meiyanto E. Pentagamavunon-1 menghambat siklus sel T47D terinduksi caspase inhibitor Z-VAD-Fmk pada fase G2-M. J Farmasi Indones 2012;5(4):180-7.
ATCC. Available from: https://www.atcc.org/Products/All/30-2007.aspx.
Dyson N. The regulation of E2F by pRB-family proteins. Genes Dev 1998;2(15):2245-62.
Lagunas-MartÃnez A, Madrid-Marina V, Gariglio P. Modulation of apoptosis by early human papillomavirus proteins in cervical cancer. Biochim Biophys Acta 2010;1805(1):6-16.
Wosikowski K, Regis JT, Robey RW, Alvarez M, Buters JT, Gudas JM, et al. Normal p53 status and function despite the development of drug resistance in human breast cancer cells. Cell Growth Differ 1995;6(11):1395-403.
Janicke RU, Sprengart ML, Wati MR, Porter AG. Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J Biol Chem 1998;273(16):9357-60.
Lim LY, Vidnovic N, Ellisen LW, Leong CO. Mutant p53 mediates survival of breast cancer cells. Br J Cancer 2009;101(9):1606-12.
Chaitanya GV, Alexander JS, Babu PP. PARP-1 cleavage fragments: Signatures of cell-death proteases in neurodegeneration. Cell Commun Signal 2010;8(31):1-11.
Choundhuri T, Pal S, Agrawal ML, Dasa T, Sa G. Curcumin induces apoptosis in human breast cancer cell trough p53-dependen bax induction. FEBS Lett 2002;512(1-3):334-40.
Pannoa ML, Giordanoa F, Mastroiannib F, Morelli C, Brunelli E, Palma MG, et al. Evidence that low doses of taxol enhance the functional transactivatory properties of p53 on p21 waf promoter in MCF-7 breast cancer cells. FEBS Lett 2006;580(9):2371-80.
Srivastava RK, Srivastava AR, Korsmeyer SJ, Nesterova M, Cho-Chung YS, Longo DL. Involvement of microtubules in the regulation of Bcl2 phosphorylation and apoptosis through cyclic AMP-dependent protein kinase. Mol Cell Biol 1998;18(6):3509-17.
Fortin JS, Cote MF, Deschesnes RG, Lacroix J, Patenaude A, Biancamano MO, et al. Microtubule disrupting N-phenyl-Nâ€™-(2-chloroethyl) ureas display anticancer activity on cell adhesion, P-glycoprotein and BCL-2-mediated drug resistance. Int J Pharm Pharm Sci 2014;6(2):171-9.
Devarajan E, Chen J, Multani AS, Pathak S, Sahin AA, Mehta K. Human breast cancer MCF-7 cell line contains inherently drug-resistant subclones with distinct genotypic and phenotypic features. Int J Oncol 2002;20(5):913-20.
Zhang GP, Lu YY, Lv JC, Ou HJ. Effect of ursolic acid on caspase-3 and PARP expression of human MCF-7 cells. Zhongguo Zhong Yao Za Zhi 2006;31(2):141-4.
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