SELEKTIVITAS DAN MEKANISME MOLEKULER ANTIKANKER EKSTRAK AKTIF RIMPANG Curcuma mangga Val

ENDANG ASTUTI,DRA.,M.SI., Prof. Dr. Retno Sunarminingsih, M.Sc, Apt.

2015 | Disertasi | S3 Bioteknologi

Kanker merupakan salah satu penyakit yang menjadi masalah kesehatan masyarakat di dunia maupun di Indonesia. Terapi penyakit kanker secara umum sering tidak efektif yang ditandai dengan sel kanker menjadi resisten, terkenanya sel normal dan memberikan efek samping. Saat ini sedang digalakkan penelitian untuk menemukan antikanker yang aman dan spesifik membunuh sel kanker. Beberapa penelitian mengungkapkan rimpang kunir putih (Curcuma mangga Val.) mengandung banyak senyawa metabolit sekunder non minyak atsiri dan minyak atsiri yang memiliki aktifitas sitotoksik terhadap sel kanker. Berdasarkan potensi antikanker rimpang C. mangga Val., maka dilakukan penelitian untuk mengetahui selektifitas antikanker dan mekanisme molekuler antikanker, yaitu antara lain: menginduksi apoptosis, menghambat proliferasi, memacu sistem kekebalan tubuh terhadap sel kanker serta menekan inflamasi dan invasi. Uji sitotoksisitas ekstrak dan maserat n-heksana, ekstrak dan maserat etanol serta minyak atsiri dari empu, cabang rimpang dan campuran rimpang C. mangga Val. dilakukan menggunakan beberapa sel kanker dan sel normal. Terhadap ekstrak, maserat atau destilat C. mangga Val. dengan aktivitas sitotoksik tertinggi dilakukan identifikasi senyawa aktif, uji TUNEL dan uji imunositokimia untuk melihat ekspresi protein p53, caspase-9, Bcl-2, H-Ras, COX-2, interleukin- 10, interleukin-12 dan GABA. Hasil penelitian menunjukkan: (1) Destilat minyak atsiri lebih toksik dibandingkan ekstrak dan maserat n-heksana dan etanol rimpang C. mangga Val.; (2) Aktivitas sitotoksik minyak atsiri rimpang C. mangga Val. bersifat selektif terhadap sel myeloma, namun tidak toksik terhadap sel Vero; (3) Komponen utama minyak atsiri rimpang C. mangga Val. adalah -mirsen dan -pinen, sedangkan aktivitas sitotoksik terhadap sel kanker disebabkan oleh sinergi antara komponenkomponen dalam minyak atsiri; (4) Mekanisme molekuler antikanker minyak atsiri rimpang C. mangga Val. terhadap sel myeloma dengan meningkatkan protein proapoptosis p53 dan caspase-9; menekan produksi protein yang memacu proliferasi Bcl-2 dan H-Ras. Minyak atsiri C. mangga Val. menekan inflamasi dengan meningkatkan ekspresi interleukin-10 dan menurunkan interleukin-12. Meningkatnya interleukin-10 juga meningkatkan sistem kekebalan. Meningkatnya COX-2 akan menekan Ras-MAPK dan Bcl-2 sehingga menekan proliferasi; namun dengan meningkatnya protein GABA memungkinkan terjadinya invasi. Disimpulkan bahwa minyak atsiri C. mangga Val meningkatkan apoptosis melalui jalur mitokondria (intrinsik). Kata kunci: Curcuma mangga Val., antikanker

Cancer is still a major health problem in the world, and so in Indonesia. The nowadays cancer therapies some are not effective due to the drug resistance and bad side effect to the body. Researches on the more effective and safe drug have been proceeded for cancer diseases. It has been found that the rhizome of kunir putih (Curcuma mangga Val.) contains some active compounds with cytotoxic activities to the cancer cells. Base on that discovery, some studies had been done to identify the active compounds, to find out their sensitivity to the several cancer cells and the molecular mechanism by studying the apoptotic induction, the proliferation inhibition, and the possibility for the reducing of inflamation and invansion of the cancer, as well as the its influences to the immune system stimulation. Cytotoxicity tests had been carried out to the several cancer (Raji, HeLa, SiHa, T47D, and Myeloma) and normal (Vero) cells which had been added with the destilate (essential oil) as well as the n-hexane and ethanol extracts and maserates, of the C. mangga Val. rhizome, branch rhizome and the mixture. The most potential cytotoxic isolate then to be identified its chemical content, as well as to be studied for the expressions of the p53, caspase-9, Bcl2, H-Ras, COX-2, interleukin-10, interleukin-12 and GABA, using TUNEL and immunocytochemistry tests. The results of the studies showed that: (1) The C. mangga Val. essential oil (which contains secondary metabolites) is more cytotoxic then the n-hexane and ethanol extracts and maserates; (2) The cytotoxic activity of the C. mangga Val. essential oil is sensitive the most to myeloma cells and non toxic to the Vero cells; (3) The main components of the C. mangga Val. essential oil are -myrcene and -pinene, but the anti-cancer activity is effected by the synergy of the whole oil contents (4) Anti-cancer molecular mechanism of C. mangga Val. essential oil to myeloma cell was determined through the increasing of the pro-apoptosis protein expression of p53 and caspase-9; the un-increasing of the protein which stimulate Bcl-2 and H-Ras proliferation as well as the reducing inflamation by increasing interleukin-10 and decreasing interleukin-12 expressions. The increasing of interleukin-10 has possibility to increase of the immune system. Moreover, the increasing of COX-2 will reduce the expressions of Ras-MAPK and Bcl-2, which in turn reduces the cancer cell proliferation. However there was no influence to cancer invansion was found due to the increasing of the GABA protein expression. It is concluded that the C. mangga Val. essential oil increases cancer cell apoptosis through the mitochondrial (intrinsic) pathway. Keywords: Curcuma mangga Val., anti-cancer

Kata Kunci : Curcuma mangga Val., antikanker; Curcuma mangga Val., anti-cancer