Efek Antikanker Pentagamavunon-0 (PGV-0) terhadap sel kanker payudara T47D yang diinduksi 17-Beta-estradiol melalui mekanisme induksi Apoptosis dan penghambatan Angiogenesis

NURULITA, Nunuk Aries, Dr. Edy Meiyanto, M.Si.,Apt

2005 | Tesis | S2 Ilmu Farmasi

Pentagamavunon-0 atau PGV-0 (2,5-bis-(4’-hidroksi-3’-metoksibenzilidin) 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 antiangiogenesis PGV-0 dibandingkan dengan kurkumin pada sel T47D yang diinduksi 17-β-estradiol (E2) 10 nM, serta mekanisme molekulernya. Uji sitotoksik dan antiproliferatif PGV-0 dilakukan dengan metode MTT. Fenomena apoptosis sel T47D yang diberi perlakuan PGV-0 dan kurkumin dilihat dengan metode double stainning dengan etidium bromida-akridin oranye. Ekspresi protein p53, Bcl-2, Bax, VEGF, dan COX-2, dilihat dengan metode immunositokimia. Hasil penelitian menunjukkan nilai IC50 PGV-0 dan kurkumin adalah 6,85 μM dan 19,83 μM. PGV-0 dan kurkumin mempunyai efek antiproliferasi dan mampu memperpanjang waktu doubling time. Efek sitotoksik dan antiproliferasi PGV-0 lebih baik dibanding kurkumin. Pengamatan apoptosis dengan double staining menggunakan etidium bromida-akridin oranye, menunjukkan PGV-0 dapat memacu apoptosis sel T47D pada konsentrasi lebih rendah dibanding kurkumin. Peningkatan ekspresi p53 dan Bax serta penurunan ekspresi Bcl-2 pada level protein diduga terlibat dalam apoptosis. Efek antiangiogenetik PGV-0 dan kurkumin ditunjukkan dengan penurunan ekspresi VEGF dan COX-2 yang ditingkatkan oleh E2. efek antiangiogenesis PGV-0 lebih baik dibanding kurkumin.

Pentagamavunon-0 or PGV-0 [2,5-bis-(4’-hydroxy-3’-methoxybenzylidene)- cyclopentanone], was determined on its cytotoxicity, antiproliferative, and antiangiogenesis effects in comparation to the effect of its analogue, curcumin (1,7- bis-(4’-hydroxy-3’-methoxyphenyl)-1,6-heptadiena-3,5-dion) against 17-β-estradiol (E2) induced human breast cancer cells T47D. MTT assay was used for measurring the cytotoxic and antiproliferative effects. Apoptotic effect of T47D cells as a result of PGV-0 and curcumin treatments could be seen by ethidium bromide-acrydin orange doublestainning method. Imunocytochemistry method was used to determine p53, Bcl-2, Bax, VEGF, and COX-2 proteins expression. The results showed that PGV-0 and curcumin possesed cytotoxicity effect againts T47D cells with IC50 6,85 μM and 19,83 μM, respectively. Both compounds showed an antiproliferative properties as indicated by the prolongation of the doubling time. PGV-0 has cytotoxic and antiproliferative properties better than curcumin. PGV-0 induced apoptosis at lower concentration than that of curcumin, as showed with ethidium bromide-acrydin orange doublestainning. The increasing of p53 and Bax and decreasing of Bcl-2 expressions, might have a relationship with apoptosis. PGV-0 have antiangiogenesis properties stronger than curcumin. It was showed by decreasing of VEGF and COX-2 expressions.

Kata Kunci : PGV-0, kurkumin, T47D, 17-β-estradiol, antiproliferatif, apoptosis, angiogenesis, PGV-0, curcumin, T47D, 17-β-estradiol, antiproliferative, apoptosis, angiogenesis