title: Piper betle leaf extract enhances the cytotoxicity effect of 5-fluorouracil in inhibiting the growth of HT29 and HCT116 colon cancer cells.
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.
authors.affiliation: 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.
authors.forename: Pek Leng
authors.initials: PL
authors.lastname: Ng
authors.forename: Nor Fadilah
authors.initials: NF
authors.lastname: Rajab
authors.forename: Sue Mian
authors.initials: SM
authors.lastname: Then
authors.forename: Yasmin Anum
authors.initials: YA
authors.lastname: Mohd Yusof
authors.forename: Wan Zurinah
authors.initials: WZ
authors.lastname: Wan Ngah
authors.forename: Kar Yong
authors.initials: KY
authors.lastname: Pin
authors.forename: Mee Lee
authors.initials: ML
authors.lastname: Looi
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000008:administration & dosage*; D045325:HCT116 Cells; D019073:HT29 Cells; D041743:Herb-Drug Interactions; D006801:Humans; D008296:Malaysia; D008517:Phytotherapy; D031721:Piper betle; D010936:Plant Extracts / Q000008:administration & dosage; D018515:Plant Leaves
chemical_list: D010936:Plant Extracts; D005472:Fluorouracil
keywords: 5-Fluorouracil; Herb-drug interaction; Isobologram analysis; Piper betle L.; Piperaceae
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