Low Dose Astaxanthin Treatments Trigger the Hormesis of Human Astroglioma Cells by Up-Regulating the Cyclin-Dependent Kinase and Down-Regulated the Tumor Suppressor Protein P53.

Juhyun Shin,Ramesh Kumar Saini,Jae-Wook Oh

doi:10.3390/biomedicines8100434

Abstract

Astaxanthin (AXT) is a xanthophyll carotenoid known to have potent anti-cancer effects via upregulation of the intracellular reactive oxygen species (ROS) levels, which triggers apoptosis of cancer cells. While several studies have shown that AXT has potential as an anti-cancer drug, its effects in glioblastoma multiforme cells remain relatively unknown. In this study, we investigated the effects of AXT in the astroglioma cell lines U251-MG, T98G, and CRT-MG. We found that the response to AXT varied between cell lines. Moreover, U251-MG cells showed a specific hormetic response to AXT. At high concentrations (20–40 μM), AXT triggered apoptosis in U251-MG cells, as it has been previously shown in other cancer cell lines. However, low concentrations (4–8 μM) of AXT were found to upregulate the proliferative cell cycle. Furthermore, at low concentrations, AXT did not affect the intracellular ROS levels, while the superoxide dismutase activity increased moderately. Western blot analysis showed that treatment with a low concentration of AXT upregulated cyclin-dependent kinase (Cdk) 2 and p-Cdk2/3 levels and downregulated the expression of tumor protein p53. Thus, our results showed that AXT has a hormetic effect in the astroglioma cell line U251-MG.

Highlights

Astaxanthin (3, 30 -dihydroxy-β, β0 -carotene-4, 40 -dione, AXT) is a xanthophyll carotenoid that was first identified in lobsters and can be found in various marine organisms [1], including the microalgaeHaematococcus pluvialis, which is one of the major commercial sources of AXT [2]
In vivo and in vitro studies of its effects on cancer suggest that administration of high doses of AXT leads to cell cycle arrest and that it has pro-apoptotic properties; these effects are highly dependent on the cell line analyzed (IC50 ranging from 39 to 720 μM depending on the cell line)
The effect of AXT in the three astroglioma cell lines U251-MG, CRT-MG, and T98G were assayed via the 4-[3-(4-Iodophenyl)-2-(4-nitro-phenyl)-2H-5-tetrazolio]-1,3-benzene sulfonate-1 (WST-1) assay (Figure 1A)

Summary

Introduction

Astaxanthin (3, 30 -dihydroxy-β, β0 -carotene-4, 40 -dione, AXT) is a xanthophyll carotenoid that was first identified in lobsters and can be found in various marine organisms [1], including the microalgaeHaematococcus pluvialis, which is one of the major commercial sources of AXT [2]. In vivo and in vitro studies of its effects on cancer suggest that administration of high doses of AXT leads to cell cycle arrest and that it has pro-apoptotic properties; these effects are highly dependent on the cell line analyzed (IC50 ranging from 39 to 720 μM depending on the cell line). This indicates that AXT could potentially be used as an anti-cancer agent [8].

Methods

Results

Conclusion