Ginger Extract (Zingiber officinale Roscoe) Triggers Apoptosis in Hepatocarcinogenesis Induced Rats
Zingiber officinale Roscoe and apoptosis
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.
Keywords :
apoptosis,
Bcl-2,
caspase-8,
ginger extract,
hepatocarcinogenesis-induced rats,
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.
Kata Kunci :
apoptosis,
Bcl-2,
ekstrak halia,
kaspase-8,
tikus teraruh kanser,
Correspondance Address
Professor Dr. Yasmin Anum Mohd Yusof, Department of Biochemistry, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur.
Tel: 603-9289 5297; Fax: 603-2693 8037. Email: anum@medic.ukm.my