Pengaruh PGV-1 pada sel kanker payudara T47D yang diinduksi 17 Beta-Estradiol :: Kajian Antiproliferasi, pemacuan apoptosis, dan antiangiogenesis

MELANNISA, Rosita, Dr. Edy Meiyanto, MSi.,Apt

2004 | Tesis | S2 Ilmu Farmasi

Kanker payudara banyak diderita kaum wanita di Indonesia setelah kanker leher rahim. Metastasis tumor merupakan penyebab kematian utama pada penderitanya. Angiogenesis diperlukan oleh sel tumor untuk dapat bermetastasis secara efektif. Senyawa 17β-estradiol diketahui dapat menstimulasi proliferasi dan angiogenesis pada sel kanker payudara yang mengekspresikan reseptor estrogen (ER). Sel kanker payudara T47D mengekspresikan ER. Pentagamavunon-1 atau PGV-1 [2,5-bis(4’-hidroksi-3’,5’-dimetilbenzilidin)siklopentanon] merupakan analog kurkumin [1,7-bis-(4’- hidroksi -3’-metoksifenil)-1,6-heptadiena-3,5-dion]. Penelitian ini bertujuan untuk mengetahui efek sitotoksik, antiproliferasi, dan antiangiogenik PGV-1 dibandingkan dengan kurkumin pada sel T47D yang diinduksi 17β-estradiol 10-8 M. Hasil penelitian menunjukkan nilai IC50 PGV-1 adalah 3,16 μM lebih bersifat sitotoksik dibanding kurkumin (IC50 = 19,05 μM). PGV-1 dan kurkumin memiliki efek antiproliferasi dan mampu memperpanjang doubling time. Efek antiproliferasi PGV-1 diperoleh pada konsentrasi 0,5 μM lebih rendah dibanding kurkumin pada 15 μM. Hasil-hasil ini menunjukkan efek sitotoksik dan antiproliferasi PGV-1 lebih baik dibanding kurkumin. Pengamatan apoptosis dengan doublestainning menggunakan etidium bromida–akridin oranye menunjukkan PGV-1 memacu apoptosis sel T47D pada konsentrasi yang lebih rendah dibanding kurkumin. Peningkatan ekspresi p53 dan Bax serta penurunan ekspresi Bcl-2 pada level protein kemungkinan berperan pada pemacuan apoptosis. Ekspresi protein diamati menggunakan metode immunositokimia. PGV-1 5 μM dan kurkumin 20 μM menurunkan ekspresi VEGF pada level protein yang ditingkatkan oleh 17β-estradiol 10-8 M sehingga memungkinkan penghambatan angiogenesis. PGV-1 dan kurkumin juga menurunkan ekspresi COX-2.

Breast cancer is the most common cancer occurring in women after cervix cancer in Indonesia. Tumor metastasis is the major cause of mortality in breast cancer. For a tumor cell to metastasize effectively, it must induce angiogenesis. Compound 17β-estradiol has been shown to stimulate the proliferation and the angiogenesis of breast cancer cells which express estrogen receptor (ER). The T47D human breast cancer cell line is ER-positive. In the present study Pentagamavunon-1 or PGV-1 [2,5-bis-(4’-hydroxy-3’,5’-dimethylbenzylidene)-cyclopentanone], an analogue of curcumin [1,7-bis-(4’-hydroxy-3’-methoxyphenyl)-1,6-heptadiena-3,5-dion], were tested on their cytotoxicity, antiproliferative, and antiangiogenic effects with curcumin as a comparation in the breast cancer cell lines T47D induced by 17β-estradiol 10-8 M. The results showed that PGV-1 possesed cytotoxicity effect againts T47D cells with IC50 values 3,16 μM. This was more cytotoxic compared to curcumin (IC50 = 19,05 μM). Both compounds possesed an antiproliferative properties as indicated by the prolongation of the doubling time. PGV-1 had prolongation effect at 0,5 μM and better than curcumin at 15 μM to the cells. These results indicate that the cytotoxic and antiproliferative properties of PGV-1 are better than curcumin. Doublestainning with ethidium bromide–acridyne orange showed that PGV-1 induced T47D cells apoptosis at lower concentrations than curcumin. The increase of p53 and Bax as well as the decrease of Bcl-2 expression at the protein level which examined by immunocytochemistry methode probably induced apoptosis. PGV-1 5 μM and curcumin 20 μM could inhibit angiogenesis showed by the decerease of VEGF expression at the protein level which increase by 17β-estradiol 10-8 M. Both compounds also decereased COX-2 expression.

Kata Kunci : Obat Antikanker,PGV,1 dan Kurkumin, PGV-1, curcumin, T47D, 17β-estradiol, apoptosis, angiogenesis