Gamma-tocotrienol and hydroxy-chavicol synergistically inhibits growth and induces apoptosis of human glioma cells

BMC Complementary and Alternative Medicine

Wan Zurinah Wan Ngah¹  Norfilza Mohd Mokhtar²  Roslan Harun²  A Rahman A Jamal²  Amirah Abdul Rahman¹ 

[1] Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia;UKM Medical Molecular Biology Institute (UMBI), UKM Medical Center, Jalan Ya’acob, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia

关键词: Glioma;    Apoptosis;    Cytotoxicity;    Synergism;    Hydroxy-chavicol;    Gamma-tocotrienol;   

Others  :  830022
DOI  :  10.1186/1472-6882-14-213

 received in 2014-01-27, accepted in 2014-06-20,  发布年份 2014

【 摘 要 】

Background

Gamma-tocotrienol (GTT), an isomer of vitamin E and hydroxy-chavicol (HC), a major bioactive compound in Piper betle, has been reported to possess anti-carcinogenic properties by modulating different cellular signaling events. One possible strategy to overcome multi-drug resistance and high toxic doses of treatment is by applying combinational therapy especially using natural bioactives in cancer treatment.

Methods

In this study, we investigated the interaction of GTT and HC and its mode of cell death on glioma cell lines. GTT or HC alone and in combination were tested for cytotoxicity on glioma cell lines 1321N1 (Grade II), SW1783 (Grade III) and LN18 (Grade IV) by [3-(4,5-dimethylthiazol-2- yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)- 2H- tetrazolium, inner salt] MTS assay. The interactions of each combination were evaluated by using the combination index (CI) obtained from an isobologram.

Results

Individually, GTT or HC displayed mild growth inhibitory effects against glioma cancer cell lines at concentration values ranging from 42–100 μg/ml and 75–119 μg/ml respectively. However, the combination of sub-lethal doses of GTT + HC dramatically enhanced the inhibition of glioma cancer cell proliferation and exhibited a strong synergistic effect on 1321N1 with CI of 0.55, and CI = 0.54 for SW1783. While in LN18 cells, moderate synergistic interaction of GTT + HC was observed with CI value of 0.73. Exposure of grade II, III and IV cells to combined treatments for 24 hours led to increased apoptosis as determined by annexin-V FITC/PI staining and caspase-3 apoptosis assay, showing caspase-3 activation of 27%, 7.1% and 79% respectively.

Conclusion

In conclusion, combined treatments with sub-effective doses of GTT and HC resulted in synergistic inhibition of cell proliferation through the induction of apoptosis of human glioma cells in vitro.

【 授权许可】

   
2014 Abdul Rahman et al.; licensee BioMed Central Ltd.

【 图 表 】

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