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Abstrak :
Latar Belakang. Endometriosis ditandai dengan pertumbuhan jaringan endometrium di luar uterus, salah satunya disebabkan oleh disregulasi apoptosis sel yang memicu ketahanan sel ektopik. Asam galat dan turunannya pada beberapa penelitian mampu menghambat karsinogenesis pada beberapa cell line kanker. Penelitian kami terdahulu membuktikan asam galat dan turunannya dapat menekan proliferasi sel dan meningkatkan apoptosis sel endometriosis in vitro, namun efeknya terhadap mekanisme jalur apoptosis instrinsik belum di buktikan. Metode. Sel endometriosis berasal dari jaringan endometrium pasien laparaskopi, diisolasi secara enzimatis dan dikultur primer. Sel kultur diberi perlakuan asam galat, heptil galat, oktil galat dengan dosis 51,2 μg/ml, 102,4 μg/ml dan 153,6 μg/ml selama 48 jam, dilanjutkan induksi 10 ng/ml LPS selama 24 jam . Kelompok kontrol hanya di induksi LPS tanpa perlakuan. Ekspresi relatif mRNA Bax, Bcl-2, dan Caspase-3 dinilai dengan qRT-PCR. Hasil. Peningkatan tertinggi ekspresi mRNA Bax dan penekanan tertinggi ekspresi mRNA Bcl-2 pada oktil galat dosis 153,6 μg/ml. Peningkatan ekspresi mRNA Bax, dan penurunan ekspresi mRNA Bcl-2 akan di ikuti dengan peningkatan ekspresi mRNA Caspase-3. Secara statistik tidak terdapat perbedaan bermakna antara kelompok perlakuan dengan ekspresi mRNA Bax, Bcl-2, dan Caspase-3 (p > 0,05). Kesimpulan. Oktil galat, asam galat, dan heptil galat memiliki efek potensial pada mekanisme apoptosis intrinsik. ......Background. Endomeriosis characterized by the presence of extrauterine endometrial tissue, one of which caused by disregulation of apoptosis that contribute of endometrial ectopic survival. Our previous research has proven that gallic acid and its derivatives can suppress proliferation and induce apoptosis endometriosis cell in vitro. However, the effect of gallic acid and its derivatives on apoptosis intrinsic pathway mechanism is not proven yet. Method. Endometriosis cell from endometriosis patiens who had undergone laparascopy surgery were isolated by enzimatic reaction and primary cultured. Cultured cells treated by gallic acid, heptyl gallate and octyl gallate each with dosage 51.2 μg/ml, 102.4 μg/ml, 153.6μg/ml for 48 hours, than induced by LPS 10 ng/ml for 24 hours. Parameter research was assessed by qRT-PCR for mRNA expression of Bax, Bcl-2, Caspase-3. Result. Octyl gallate showed more effect to induce apoptosis intrinsic . Endometriosis cell were treated with octyl gallate shown increases of Bax and Caspase3 mRNA expression than decrease of Bcl-2 mRNA expression. Statistically, mean differences are not significant between treatment groups and mRNA expression (p > 0.05). Conclusion. This study exhibited that octyl gallate has a more potential effect on apoptosis intrinsic in endometriosis cell cultures followed by gallic acid and heptyl gallate and their potency as treatment for endometriosis.

Abstrak :
Pendahuluan: Asam galat adalah salah satu senyawa aktif yang dapat menyebabkan apoptosis pada sel kanker paru manusia. Aktivitas antikanker paru yang mengesankan dari asam galat mendorong dilakukannya penelitian untuk menguji aktivitas sitotoksik senyawa turunan asam galat (alkil amida galat) terhadap sel kanker paru A549. Metode: Enam senyawa alkil amida galat hasil sintesis, yaitu Senyawa metil amida galat, etil amida galat, butil amida galat, sek-butil amida galat, ters-butil amida galat, dan heksil amida galat diuji aktivitas sitotoksiknya terhadap sel kanker paru A549 dengan metode MTT Proliferation assay. Data yang dihasilkan dianalisa menggunakan analisis regresi linear untuk mendapatkan nilai IC50. Hasil uji aktivitas sitotoksik senyawa alkil amida galat hasil sintesis dibandingkan dengan hasil uji aktivitas sitotoksik asam galat sebagai senyawa asli dan doxorubicin selaku kontrol positif. Hasil: Jika dibandingkan dengan asam galat (IC50: 23.2 μM) dan doxorubicin (IC50: 31.1 μM), keenam senyawa alkil amida galat, yaitu metil amida galat, etil amida galat, butil amida galat, sek-butil amida galat, ters-butil amida galat, dan heksil amida galat memperlihatkan sitotoksisitas yang lebih kuat terhadap sel kanker paru A549 dengan nilai IC50 berkisar dari 5.4 μM hingga 30.0 μM. Kesimpulan: Enam senyawa alkil amida galat berpotensi dikembangkan lebih lanjut sebagai agen antikanker paru. ......Objective: Gallic acid has shown its potential to induce apoptosis in lung cancer cells. Its impressive anti-lung cancer agent prompted us to conduct research that is aimed to evaluate six alkyl amide derivatives of gallic acid against lung cancer A549 cells. Methods: six synthesized compounds of alkyl amide gallate, which are methyl amide gallate, ethyl amide gallate, butyl amide gallate, sec-butyl gallate, ters-butyl gallate and hexyl amide gallate, will be evaluated their cytotoxicities agains lung A549 cells by MTT Proliferation assay. Linear regression analysis is used to analyzed the data to generate IC50 value. Cytotoxicity results of alkyl amide gallates will be compared with cytotoxicity result of gallic acid as an original compound and with doxorubicin as positive control. Results: Compared with gallic acid (IC50 23.2 μM) and doxorubicin (IC50 31.1 μM), six derivatives of aklyl amide gallates (methyl-, butyl-, sec-butyl-, ters- butyl, and hexyl amide gallate) shows better cytotoxic activity against lung A549 cells, with IC50 value range from 5.4 μM to 30.0 μM. Conclusion: Six compounds of Alkyl amide gallate could be further developed as anti-lung cancer agent.