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 (IC 50 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.
Background: Piper betle (PB) leaves (daun sirih in Malay language) extract has been demonstrated to have anticarcinogenic activities in the experimental systems. It has been found the PB leaves extract could enhance the cytotoxic effect of other anticancer drugs in cancer cells. The aim of this study is to investigate the combination effect of PB and 5-fluorouracil (5-FU) in enhancing the cytotoxic potential using colon cancer cell lines. Methods:We first examined the effect of PB leaves extract on colon cancer cells. Next, we examined whether PB leaves extract could increase the sensitivity of the cells to 5-FU. Isobologram analysis was carried out to elucidate PB-5FU interaction. Apoptotic features of the treated cells were then revealed by Annexin V/ PI stain. HPLC was performed to exclude any possible chemical interaction between the compounds.Result: IC50 of 5-FU treated HT 29 and HCT 116 was 130.0µM and 12.5µM, respectively at 72 hours. IC50 of PB-treated HT 29 (200.0µg/ml) and HCT 116 cells (187.5µg/ml) was observed after 36 hours of treatment. In the presence of PB extract, the cytotoxic effect of 5-FU was observed at a lower dose (12.5µM) and a shorter time (24 hours Conclusion:In the presence of PB, a lower dosage of 5-FU is required to achieve the maximum drug effect. PB works synergistically with 5-FU in controlling cancer cell growth. However our current result showed this interaction may not solely contribute to the apoptosis pathway. Further investigation should be performed to elucidate the possible mechanism.
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