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| Piper betle leaf extract enhances the cytotoxicity effect of 5-fluorouracil in inhibiting the growth of HT29 and HCT116 colon cancer cells |
| Pek Leng Ng, Nor Fadilah Rajab, Sue Mian Then, Yasmin Anum Mohd Yusof, Wan Zurinah Wan Ngah, Kar Yong Pin, Mee Lee Looi |
| Department of Biomedical Sciences, Faculty of Allied Health, Universiti Kebangsaan Malaysia (UKM), Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia; UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia (UKM), Jalan Yaacob Latiff, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia; School of Biomedical Science, University of Nottingham Malaysia Campus, 43500 Semenyih, Selangor, Malaysia; Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM), Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia; Forest Research Institute Malaysia (FRIM), 52109 Kuala Lumpur, Kepong, Malaysia; School of Biosciences, Taylor's University, Lakeside Campus, 47500 Subang Jaya, Selangor, Malaysia |
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Abstract Objective: The combination effect of Piper betle (PB) and 5-fluorouracil (5-FU) in enhancing the cytotoxic potential of 5-FU in inhibiting the growth of colon cancer cells was investigated. Methods: HT29 and HCT116 cells were subjected to 5-FU or PB treatment. 5-FU and PB were then combined and their effects on both cell lines were observed after 24 h of treatment. PB-5-FU interaction was elucidated by isobologram analysis. Apoptosis features of the treated cells were revealed by annexin V/PI stain. High-performance liquid chromatography (HPLC) was performed to exclude any possible chemical interaction between the compounds. Results: In the presence of PB extract, the cytotoxicity of 5-FU was observed at a lower dose (IC50 12.5 µmol/L) and a shorter time (24 h) in both cell lines. Both cell lines treated with 5-FU or PB alone induced a greater apoptosis effect compared with the combination treatment. Isobologram analysis indicated that PB and 5-FU interacted synergistically and antagonistically in inhibiting the growth of HT29 and HCT116 cells, respectively. Conclusions: In the presence of PB, a lower dosage of 5-FU is required to achieve the maximum drug effect in inhibiting the growth of HT29 cells. However, PB did not significantly reduce 5-FU dosage in HCT116 cells. Our result showed that this interaction may not solely contribute to the apoptosis pathway.
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Received: 26 November 2013
Published: 05 August 2014
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