JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B 2014 Vol.15 No.8 P.692-700

Piper betle leaf extract enhances the cytotoxicity effect of 5-fluorouracil in inhibiting the growth of HT29 and HCT116 colon cancer cells*

Author(s): Pek Leng Ng¹, Nor Fadilah Rajab¹, Sue Mian Then^2,3, Yasmin Anum Mohd Yusof⁴, Wan Zurinah Wan Ngah^2,4, Kar Yong Pin⁵, Mee Lee Looi⁶
Affiliation(s): 1. Department of Biomedical Sciences, Faculty of Allied Health, Universiti Kebangsaan Malaysia (UKM), Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia; more
Corresponding email(s): MeeLee.Looi@taylors.edu.my
Key Words: Piperaceae , Piper betle L., 5-Fluorouracil, Isobologram analysis, Herb-drug interaction

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Pek Leng Ng, Nor Fadilah Rajab, Sue Mian Then, Yasmin Anum Mohd Yusof, Wan Zurinah Wan Ngah, Kar Yong Pin, Mee Lee Looi. Piper betle leaf extract enhances the cytotoxicity effect of 5-fluorouracil in inhibiting the growth of HT29 and HCT116 colon cancer cells[J]. Journal of Zhejiang University Science B, 2014, 15(8): 692-700.

@article{title="Piper betle leaf extract enhances the cytotoxicity effect of 5-fluorouracil in inhibiting the growth of HT29 and HCT116 colon cancer cells",
author="Pek Leng Ng, Nor Fadilah Rajab, Sue Mian Then, Yasmin Anum Mohd Yusof, Wan Zurinah Wan Ngah, Kar Yong Pin, Mee Lee Looi",
journal="Journal of Zhejiang University Science B",
volume="15",
number="8",
pages="692-700",
year="2014",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1300303"
}

%0 Journal Article
%T Piper betle leaf extract enhances the cytotoxicity effect of 5-fluorouracil in inhibiting the growth of HT29 and HCT116 colon cancer cells
%A Pek Leng Ng
%A Nor Fadilah Rajab
%A Sue Mian Then
%A Yasmin Anum Mohd Yusof
%A Wan Zurinah Wan Ngah
%A Kar Yong Pin
%A Mee Lee Looi
%J Journal of Zhejiang University SCIENCE B
%V 15
%N 8
%P 692-700
%@ 1673-1581
%D 2014
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1300303

TY - JOUR
T1 - Piper betle leaf extract enhances the cytotoxicity effect of 5-fluorouracil in inhibiting the growth of HT29 and HCT116 colon cancer cells
A1 - Pek Leng Ng
A1 - Nor Fadilah Rajab
A1 - Sue Mian Then
A1 - Yasmin Anum Mohd Yusof
A1 - Wan Zurinah Wan Ngah
A1 - Kar Yong Pin
A1 - Mee Lee Looi
J0 - Journal of Zhejiang University Science B
VL - 15
IS - 8
SP - 692
EP - 700
%@ 1673-1581
Y1 - 2014
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1300303

Abstract
Chinese Summary
Academic Network
Reviewer Comment

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.

蒌叶提取物增强5-氟尿嘧啶对结肠癌细胞HT29和HCT116的生长抑制作用

研究目的：探讨蒌叶（PB）提取物对5-氟尿嘧啶（5-FU）抑制结肠癌细胞HT29和HCT116生长的影响。
研究方法：HT29和HCT116细胞分别给予PB、5-FU以及两种药物联合治疗24小时，应用等效线图法分析PB和5-FU的药效学相互作用，AnnexinV/PI染色法检测HT29和HCT116细胞的凋亡情况，高效液相色谱法排除PB和5-FU间任何可能的相互化学作用。
重要结论：联合PB，低剂量5-FU可以在短时间内起到细胞毒作用，而单独应用PB或5-FU治疗较联合治疗可以诱导更多细胞发生凋亡。进一步采用等效线图法分析显示PB和5-FU的联合作用在抑制结肠癌细胞HT29和HCT116的生长中分别体现出协同和拮抗作用。因此可以认为在HT29细胞中，PB使得较低剂量5-FU发挥最大抑制结肠癌细胞生长效果，然而在HCT116细胞中，PB没有显著降低5-FU的药物浓度，说明PB和5-FU的相互作用不仅仅体现在诱导细胞凋亡方面。
胡椒科；蒌叶；5-氟尿嘧啶；等效线图法；草药-药物相互作用

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蒌叶提取物增强5-氟尿嘧啶对结肠癌细胞HT29和HCT116的生长抑制作用

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