Synergistic Effect of Areca catechu L. Ethanolic Extract and Its Chloroform Fraction with Doxorubicin on MCF7
Abstract
Ekstrak etanol biji buah pinang (Areca catechu L.) menunjukkan efek sitotoksik pada sel kanker MCF7 dan WiDr. Penelitian ini bertujuan untuk mempelajari efek sinergisme antara ekstrak etanol biji buah pinang (AE) dan fraksi kioroforrnnya (ACF) dengan doxorubicin (Dox) dalam pemacuan apoptosis sel MCF7. Ekstrak etanol dipartisi dengan n-heksan dan kloroform untuk mendapatkan fraksi kloroforin. Efek sitotoksik.AE, ACF, dan Dox pada perlakuan tunggal dan kornbinasi ditentukan dengan metode MTT. Penganiatan apoptosis dilakukan dengan pengecatan DNA dengan akridin oranye-etidium bromida (double staining). Imunositokimia dilakukan untuk melihat ekspresi COX-2 dan Bax. Kombinasi Dox 100, 250, 334, dan 500 nM dengan AE 8 µg/ml; Dox 100 nM dengan AE 20 µg/ml; serta Dox 100 dan 250 nM dengan ACF 7 dan 18 µg/ml memperlihatkan efek sinergistis yang kuat (CI 0,1-0,3). Sernentara itu, kombinasi Dox 250, 334, dan 500 nM dengan AE 20, 27, dan 40 µg/ml; Dox 100 nM dengan AE 27 dan 40 µg/ml; Dox 100 nM dengan AE 20 µg/mi; Serta 500 nM dengan ACF 24 dan 35 µg/ml menunjukkan efek sinergistis (CI 0,3-0,7). Secara keseluruhan, kombinasi AE dan ACF dengan Dox memperiihatkan efek sinergistis pada MCF7 dengan indeks kombinasi (CI) kurang dari 0,9 (P<0,05). Periakuan kombinasi juga memacu apoptosis. Penekanan ekspresi Bcl-2 terjadi padaperlakuan kombinasi ACF-Dox. Hasil penelitian ini menunjulckan bahwa koinbinasi AE dan ACF dengan Dox memberikan efek sinergistis dalam pemacuan apoptosis dengan kemungkinan mekanisme meialui penekanan ekspresi Bcl-2.
References
2. Wyllie A, Donahue V, Fischer B, Hill D, Keesey J, and Manzow S. Cell death apoptosis and necrosis. Rosche Diagnostic Corporation. 2000.
3. Leigh MJ. Health benefits of grape seed proanthocyanidin extract (GSPE). Nutrition Noteworthy 2003.6(1):article 5.
4. Thurston DE and Lobo SGM. The chemotherapy of cancer, introduction to the principles of drug design and action. Australia: Harwood academic publishers; 1998.
5. Massart C, Barbet R, Genetet N, and Gibassier J. Doxorubicin induces Fas-mediated apoptosis in human thyroid carcinoma cells. Thyroid 2004. 14(4):263-70.
6. Tyagi AK, Agarwal C, Chan DCF, Agarwal R. Synergistic anti-cancer effects of silibinin with conventional cytotoxic agents doxorubicin, cisplatin and carboplatin against human breast carcinoma MCF7 and MDA-MB468 cells. Oncology Reports. 2004. 11:493-9.
7. Wattanapitayakul SK, Chularojmontri L, Herunsalee A, Charuchongkolwongse S, Niumsakul S, and Bauer JA. Screening of antioxidants from medicinal plants for cardioprotective effect against doxorubicin toxicity. Basic & Clin Pharm & Toxic. 2005. 96:80.
8. Meiyanto E, Susidarti RA, Handayani S, and Rahmi F. Ekstrak etanolik biji buah pinang (Areca catechu L.) sebagai agen kemopreventif pada sel kanker payudara resisten agen kemoterapi (MCF7). Maj alah Farmasi Indonesia. 2008.19(1):12-19.
9. Meiyanto E, Handayani S, and Susidarti RA. Chloroform fraction of areca (Areca catechu L.) induce apoptosis and decrease Bcl-2 expression on MCF7 cells. 2008. Manuscript to be published..
10. Handayani S, Meiyanto E, and Susidarti RA. Areca (Areca catechu L.) seeds ethanolic extract and its chloroform fraction induce apoptosis and decrease COX-2 expression on WiDr cells. Proceeding The International symposium on Molecular Targeted Therapy. ISBN: 978-979-95107-6-1. Faculty of Pharmacy UGM; 2008. p. 67-74.
11. Menchetner E, Kyshtoobayeva A, Zonis S, Kim H, Stroup R, Garcia R, et al. Levels of multidrug resistance (mdrl) p-glycoprotein expression by human breast cancer correlate with in vitro resistance to taxol and doxorubicin. Clin Can Res, 1998.4:389-98.
12. Aouali N, Morjani H, Trussardi A, Soma E, Giroux B, and Manfait M. Enhanced cytotoxicity and nuclear accumulation of doxorubicin-loaded nanospheres in human breast cancer MCF7 cells expressing mrpl. Int J Oncol. 2003.23:1195-201.
13. Reynolds CP, and Maurer BJ. Evaluating response to antineoplastic drug combinations in tissue culture models. Methods Mol Med .2005.110:173-83.
14. Butt AI, Firth SM, King MA, and Baxter RC. Insulin-like growth factor-binding protein-3 modulates expression of bax and bcl-2 and potentiates p53-independent radiation-induced apoptosis in human breast cancer cells. J Biol Chem. 2000. 275(50):39174-181.
15. Amundson SA, Myers TG, Scudiero D, Kitada S, Reed J C, and Fomace AJ. An informatics approach identifying markers of chemosensitivity in human cancer cell lines. Cancer Res. 2000.60:6101-110.
16. Simstein R, Burow M, Parker A, Weldon C, and Beckman B. apoptosis, chemoresistance, and breast cancer: insights from the MCF7 cell model system. Exp Biol Med. 2003.228:995-1003.
17. Sukla S, and Gupta S. Suppression of constitutive and tumor necrosis factor K-induced nuclear factor (NF)-ƙB activation and induction of apoptosis by apigenin in human prostate carcinoma PC-3 cells: correlation with down-regulation of NF-KB-responsive genes. Clin Can Res. 2004. 10:3169-178.
Licencing
All articles in Jurnal Ilmu Kefarmasian Indonesia are an open-access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which permits unrestricted non-commercial used, distribution and reproduction in any medium.
This licence applies to Author(s) and Public Reader means that the users mays :
- SHARE:
copy and redistribute the article in any medium or format - ADAPT:
remix, transform, and build upon the article (eg.: to produce a new research work and, possibly, a new publication) - ALIKE:
If you remix, transform, or build upon the article, you must distribute your contributions under the same license as the original. - NO ADDITIONAL RESTRICTIONS:
You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
It does however mean that when you use it you must:
- ATTRIBUTION: You must give appropriate credit to both the Author(s) and the journal, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
You may not:
- NONCOMMERCIAL: You may not use the article for commercial purposes.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.