Wee Lee Heng, Morad Noor Azian, Aan Goon Jo, Makpol Suzana, Wan Ngah Wan Zurinah, Mohd Yusof Yasmin Anum
Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Malaysia E-mail :
Asian Pac J Cancer Prev. 2015;16(15):6549-56. doi: 10.7314/apjcp.2015.16.15.6549.
The PI3K-Akt-mTOR, Wnt/β-catenin and apoptosis signaling pathways have been shown to be involved in genesis of colorectal cancer (CRC). The aim of this study was to elucidate whether combination of Gelam honey and ginger might have chemopreventive properties in HT29 colon cancer cells by modulating the mTOR, Wnt/β-catenin and apoptosis signaling pathways. Treatment with Gelam honey and ginger reduced the viability of the HT29 cells dose dependently with IC50 values of 88 mg/ml and 2.15 mg/ml respectively, their while the combined treatment of 2 mg/ml of ginger with 31 mg/ml of Gelam honey inhibited growth of most HT29 cells. Gelam honey, ginger and combination induced apoptosis in a dose dependent manner with the combined treatment exhibiting the highest apoptosis rate. The combined treatment downregulated the gene expressions of Akt, mTOR, Raptor, Rictor, β-catenin, Gsk3β, Tcf4 and cyclin D1 while cytochrome C and caspase 3 genes were shown to be upregulated. In conclusion, the combination of Gelam honey and ginger may serve as a potential therapy in the treatment of colorectal cancer through inhibiton of mTOR, Wnt/β catenin signaling pathways and induction of apoptosis pathway.
PI3K-Akt-mTOR、Wnt/β-连环蛋白和凋亡信号通路已被证明与结直肠癌（CRC）的发生有关。本研究的目的是通过调节mTOR、Wnt/β-连环蛋白和凋亡信号通路，阐明吉拉蜂蜜和生姜的组合是否对HT29结肠癌细胞具有化学预防特性。用吉拉蜂蜜和生姜处理可剂量依赖性地降低HT29细胞的活力，IC50值分别为88mg/ml和2.15mg/ml，而2mg/ml生姜与31mg/ml吉拉蜂蜜的联合处理可抑制大多数HT29细胞的生长。吉拉蜂蜜、生姜及其组合均以剂量依赖性方式诱导凋亡，联合处理的凋亡率最高。联合处理下调了Akt、mTOR、Raptor、Rictor、β-连环蛋白、Gsk3β、Tcf4和细胞周期蛋白D1的基因表达，而细胞色素C和半胱天冬酶3基因则被上调。总之，吉拉蜂蜜和生姜的组合可能通过抑制mTOR、Wnt/β-连环蛋白信号通路和诱导凋亡途径，成为治疗结直肠癌的潜在疗法。
