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Ginger Extract (Zingiber officinale Roscoe) Triggers Apoptosis in Hepatocarcinogenesis Induced Rats

Original article

Abstrak

Ekstrak halia telah dilaporkan oleh kumpulan kami sebelum ini yang ianya mempunyai kesan antikanser dan antioksidan dengan menurunkan beban tumor dan peroksidasi lipid pada tikus teraruh kanser. Kajian ini melihat pada pengekspresan protein pro-apoptosis kaspase-8 dan protein anti-apoptosis Bcl-2 pada tikus teraruh kanser. Tiga puluh ekor tikus Wistar dibahagi kepada lima kumpulan ber­dasarkan pada diet yang diberi, iaitu i) kawalan (makanan asas), ii) minyak zaitun iii) ekstrak halia (100 mg/kg berat badan) iv) diet kurang kolin + etionin dalam minuman, CDE (untuk mengaruh kanser) dan v) tikus teraruh kanser, CDE + ekstrak halia. Tikus dibunuh pada minggu ke-lapan dan tisu hepar dikeluarkan untuk pengesanan protein pro-apoptosis dan anti-apoptosis, kaspase-8 dan Bcl-2 melalui kaedah imunohistoki­mia. Pengamatan H&E menujukkan terdapat banyak sel oval yang mengesahkan ter­dapat kanser hepar pada kumpulan yang menerima diet CDE. Terdapat 91.6% (11/12) sampel dari kumpulan CDE yang menunjukkan kehadiran sel oval dan pengeksresan Bcl-2. Tetapi apabila kumpulan CDE dirawat dengan ekstrak halia, sel oval dan peng-ekspresan Bcl-2 me­nurun kepada 8.4% (1/12). Bagi kaspase-8 pula, 41.7% (5/12) sampel dari kumpulan CDE menunjukkan pewarnaan positif dan meningkat ke 100% (12/12) apabila dirawat dengan ekstrak halia. Penemuan dari kajian ini menun­jukkan ekstrak halia mempunyai kesan antikanser dengan mengaruh apoptosis melalui pe­ningkatan protein pro apop­tosis, kaspase-8, dan penurunan protein anti-apoptosis Bcl-2.

Abstract

Ginger extract has been reported previously by our group to exhibit anticancer and an­tioxidant effects by reducing tumour burden and lipid peroxidation respectively in he­patocarcinogenesis induced rats. The current study examined the expression of pro-apoptotic protein caspase-8 and anti-apoptotic protein Bcl-2 in hepatocarcinogenesis treated rats. Thirty normal male Wistar rats were divided into 5 groups based on the diet given: i) control (normal rat chow), ii) olive oil, iii) ginger extract (100mg/kg body weight), iv) choline deficient diet + ethionine, CDE (to induce liver cancer) and v) CDE+ ginger extract. Rats were killed at week 8, and liver tissues were excised for immuno­histochemical study to identify pro-apoptotic and anti-apop­totic proteins, caspase-8 and Bcl-2. The observation on H&E staining confirmed the CDE diet induced liver can­cer as indicated by the presence of numerous oval cells.Identification of Bcl-2 expres­sion showed that 91.6% (11/12) of the samples from the CDE group revealed positive staining while treatment with ginger extract however inhi­bited the expression with only 8.4% (1/12) samples showing positive staining for Bcl-2. As for caspase-8 protein, 41.7% (5/12) of the samples from CDE group showed posi­tive staining, which in­creased to 100% (12/12) with ginger extract treatment. Our findings suggest that gin­ger extract has an anticancer effect by inducing apoptosis in liver cancer cells via up-regulation of the expression of pro-apoptotic protein, caspase-8 and down-regulation of the expression of anti-apoptotic protein Bcl-2.