Anticancer activity of an extract from needles and twigs of Taxus cuspidata and its synergistic effect as a cocktail with 5-fluorouracil

Weihu Shang,Meilin Zhu,Mei Han,Jinglei Du,Wei Wang,Wei Yin,Jinping Qiao,Chenxin Gu,Weidong Lu

doi:10.1186/1472-6882-11-123

Weihu Shang, Meilin Zhu + Show 7 more

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https://doi.org/10.1186/1472-6882-11-123

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Abstract

BackgroundBotanical medicines are increasingly combined with chemotherapeutics as anticancer drug cocktails. This study aimed to assess the chemotherapeutic potential of an extract of Taxus cuspidata (TC) needles and twigs produced by artificial cuttage and its co-effects as a cocktail with 5-fluorouracil (5-FU).MethodsComponents of TC extract were identified by HPLC fingerprinting. Cytotoxicity analysis was performed by MTT assay or ATP assay. Apoptosis studies were analyzed by H & E, PI, TUNEL staining, as well as Annexin V/PI assay. Cell cycle analysis was performed by flow cytometry. 5-FU concentrations in rat plasma were determined by HPLC and the pharmacokinetic parameters were estimated using 3p87 software. Synergistic efficacy was subjected to median effect analysis with the mutually nonexclusive model using Calcusyn1 software. The significance of differences between values was estimated by using a one-way ANOVA.ResultsTC extract reached inhibition rates of 70-90% in different human cancer cell lines (HL-60, BGC-823, KB, Bel-7402, and HeLa) but only 5-7% in normal mouse T/B lymphocytes, demonstrating the broad-spectrum anticancer activity and low toxicity to normal cells of TC extract in vitro. TC extract inhibited cancer cell growth by inducing apoptosis and G2/M cell cycle arrest. Most interestingly, TC extract and 5-FU, combined as a cocktail, synergistically inhibited the growth of cancer cells in vitro, with Combination Index values (CI) ranging from 0.90 to 0.26 at different effect levels from IC50 to IC90 in MCF-7 cells, CI ranging from 0.93 to 0.13 for IC40 to IC90 in PC-3M-1E8 cells, and CI < 1 in A549 cells. In addition, the cocktail had lower cytotoxicity in normal human cell (HEL) than 5-FU used alone. Furthermore, TC extract did not affect the pharmacokinetics of 5-FU in rats.ConclusionsThe combinational use of the TC extract with 5-FU displays strong cytotoxic synergy in cancer cells and low cytotoxicity in normal cells. These findings suggest that this cocktail may have a potential role in cancer treatment.

Highlights

Botanical medicines are increasingly combined with chemotherapeutics as anticancer drug cocktails
DaKeSu, a Taxus cuspidata (TC) extract of TC needles and twigs produced by artificial cuttage, has been under preclinical and clinical investigation in China as a botanical medicinal product [17,18]
The aim of this paper is to evaluate the efficacy of the extract of TC needles and twigs produced by artificial cuttage as a source of useful anticancer agents and the co-efficacy at the cellular level of a cocktail combining TC extract and 5-FU

Summary

Introduction

Botanical medicines are increasingly combined with chemotherapeutics as anticancer drug cocktails. This study aimed to assess the chemotherapeutic potential of an extract of Taxus cuspidata (TC) needles and twigs produced by artificial cuttage and its co-effects as a cocktail with 5-fluorouracil (5-FU). Taxus cuspidata (TC), called Japanese yew, is an evergreen tree with anticancer and anti-inflammatory activities [14,15,16]. DaKeSu, a TC extract of TC needles and twigs produced by artificial cuttage, has been under preclinical and clinical investigation in China as a botanical medicinal product [17,18]. Chinese language sources have reported animalbased and preclinical studies showing DaKeSu activity against breast, lung, and digestive tract cancers [17,18], but the anticancer spectrum and mechanism of the extract have not been studied in detail

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