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

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.

Astaxanthin Sensitizes Low SOD2-Expressing GBM Cell Lines to TRAIL Treatment via Pathway Involving Mitochondrial Membrane Depolarization

“…These results show that unlike previously investigated cancer cell lines [21], the anticancer ability of AXT is restricted in GBM cell lines. This is consistent with our previous study showing that AXT has only a moderate apoptotic effect and shows beneficial effects in GBM cells [32].…”

Protopine/Gemcitabine Combination Induces Cytotoxic or Cytoprotective Effects in Cell Type-Specific and Dose-Dependent Manner on Human Cancer and Normal Cells

“…Notably, HDFs exhibited a biphasic dose response to PRO (150 μM)/GEM treatments, indicating that, similarly to other natural compounds and also to some chemotherapeutics [ 32 , 33 , 34 , 35 ], PRO in combination with GEM may induce a hormetic effect. In addition, PRO/GEM treatments caused a hormetic response in MCF-7 cancer cells, suggesting a cautious use of natural compounds as anti-cancer agents.…”

“…Hormesis is a phenomenon of biphasic dose response in which a compound usually exhibits stimulatory or beneficial effects at low doses and inhibitory or toxic effects at high doses [ 32 , 33 , 34 , 35 ]. Hormetic effect should be considered in cancer therapy in order to optimize treatment.…”

“…Our studies showed that PRO exerted a hormetic effect on PANC-1 cells, showing cytoprotection at low dose and cytotoxicity at higher doses. It is known that several tumor cell lines displayed biphasic dose responses following treatments with a wide range of agents including phytocompounds [ 33 , 34 , 35 ]; some molecular mechanisms underlying hormesis have been investigated in cultured cells and very few in animal models [ 33 , 34 , 35 ]. Our results are in line with previous studies reporting antiproliferative activity of PRO in MCF-7, cervical cancer HeLa cells, human osteosarcoma U2OS cells, prostate PC-3 and breast MDA-MB-231 cancer cells, and low or no cytotoxicity in non-tumor cells, such as HUVECs and lipopolysaccharide-activated murine macrophages (Raw 264.7 cells) [ 12 , 21 , 23 , 36 ].…”

Study on the Enhancement of Immune Function of Astaxanthin from Haematococcus pluvialis

“…It has been shown that it can inhibit lipid peroxidation and DNA damage, exerting neuroprotective effects. In addition, astaxanthin has been shown to affect the processes of tumor cell production, growth and apoptosis [16,17].…”