α‐hederin potentiates 5‐FU antitumor activity in human colon adenocarcinoma cells

Abstract

The aim of this study was to investigate the ability of alpha-hederin to improve the efficacy of widely prescribed 5-fluorouracil (5-FU) in a human colon adenocarcinoma model. Drug combinations of alpha-hederin and 5-FU using both fixed-concentration and combination index methods were performed in vitro in HT-29 cells. The results showed that alpha-hederin at sub-IC(50) cytotoxic concentrations enhanced 5-FU cytotoxicity about 3.3-fold (p < 0.001). Simultaneous combination of alpha-hederin and 5-FU at their IC(50) ratio showed either a synergistic effect at a moderate cytotoxic range (25% of cell growth inhibition) or an antagonistic effect at a high level of growth inhibition. The data indicate therefore that it is possible to optimize colorectal cancer cell sensitivity to 5-FU with alpha-hederin.

Effects of Hedera helix L. extracts on rat prostate cancer cell proliferation and motility

“…Previously, researchers have been focused on in vitro and in vivo studies using saponins and their derivatives obtained from various parts (including, leaves or fruits) of herbal sources, and certain Hedera species (18,(28)(29)(30). Triterpenoid saponins such as α-hederin, β-hederin, δ-hederin, hederacosides A-I, hederacolchisides (A, A 1 and B) and hederagenin are the primary phytochemical components in Hedera spp.…”

“…Saponin derivatives isolated from Hedera spp. (18,28) and other plants (29,30) produce antiproliferative, antitumor and cytotoxic effects (18,28), as well a range of other biological activities [including, antimicrobial (19), antifungal (20), anthelmintic (21) and antileishmanial (22)]. In the present study, crude extracts of H. helix leaves and fruits were used.…”

“…Danloy et al (17) reported that α-hederin isolated from H. helix was cytotoxic against B16 mouse melanoma and 3T3 fibroblast cell lines. α-hederin isolated from H. helix leaves potentiated the antitumor activity of 5-fluorouracil in the HT-29 human colon adenocarcinoma cell line (28). Researchers have isolated α-hederin or hederagenin from various plants (29,30).…”

α‐Hederin induces the apoptosis of gastric cancer cells accompanied by glutathione decrement and reactive oxygen species generation via activating mitochondrial dependent pathway

“…Further researches indicated that α‐hederin could induce autophagic cell death through activation of reactive oxygen species (ROS) dependent adenosine monophosphate‐activated protein kinase/mammalian target of rapamycin signaling pathway and inhibit interleukin 6‐induced epithelial‐to‐mesenchymal transition through disruption of JAK2/STAT3 signaling pathway (Sun et al, ; Sun et al, ). Additionally, α‐hederin has been shown ability to potentiate the efficacy of widely prescribed 5‐fluorouracil in a human colon cancer cell line HT‐29, particularly for the membrane alterations as a biological membrane‐perforating saponin (Bun et al, ). The researches mentioned above although invaluably identified the antitumor activity of α‐hederin, the molecular mechanisms underlying α‐hederin‐induced apoptosis are still far from being fully elucidated.…”

Determination of α-hederin in rat plasma using liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) and its application to a pharmacokinetic study

“…4 In addition, a-hederin enhanced 5-uorouracil cytotoxicity in vitro and promoted its antitumor activity when co-prescribed with a-hederin. 5 a-Hederin induced the contraction of isolated rat stomach strips 6,7 due to the inux of calcium 8 and increased the b-adrenoceptor-mediated relaxation of airway smooth muscle. 9 It is well known that rational drug discovery requires an early appraisal of pharmacokinetic (PK) properties.…”