Vitamin C effect on mitoxantrone-induced cytotoxicity in human breast cancer cell lines.

Angela Sorice,Susan Costantini,Francesca Capone,Giuseppe Castello,Eliana Guerriero,Gabriella Storti,Ying-Jan Wang,Virginia Napolitano,Giovanni Colonna

doi:10.1371/journal.pone.0115287

Abstract

In recent years the use of natural dietary antioxidants to minimize the cytotoxicity and the damage induced in normal tissues by antitumor agents is gaining consideration. In literature, it is reported that vitamin C exhibits some degree of antineoplastic activity whereas Mitoxantrone (MTZ) is a synthetic anti-cancer drug with significant clinical effectiveness in the treatment of human malignancies but with severe side effects. Therefore, we have investigated the effect of vitamin C alone or combined with MTZ on MDA-MB231 and MCF7 human breast cancer cell lines to analyze their dose-effect on the tumor cellular growth, cellular death, cell cycle and cell signaling. Our results have evidenced that there is a dose-dependence on the inhibition of the breast carcinoma cell lines, MCF7 and MDA-MB231, treated with vitamin C and MTZ. Moreover, their combination induces: i) a cytotoxic effect by apoptotic death, ii) a mild G2/M elongation and iii) H2AX and mild PI3K activation. Hence, the formulation of vitamin C with MTZ induces a higher cytotoxicity level on tumor cells compared to a disjointed treatment. We have also found that the vitamin C enhances the MTZ effect allowing the utilization of lower chemotherapic concentrations in comparison to the single treatments.

Highlights

Breast cancer is the most common cause of cancer death among women (522.000 deaths in 2012) and the most frequently diagnosed cancer in 140 of 184 countriesPLOS ONE | DOI:10.1371/journal.pone.0115287 December 22, 2014Vitamin C Effect on Mitoxantrone-Induced Cytotoxicity worldwide [1]
MTZ and vit C cytotoxic effects were evaluated on MCF7 and MDA-MB231 cell lines by Sulforhodamine B (SRB) assay to identify the concentrations at which the cell growth was inhibited by 50%
After 48 h of treatment with MTZ and vit C, compared to non treated cells, MCF7 reached an inhibition corresponding to IC50 at 1.17 mM and 1.5 mM dose, whereas MDA-MB23 reached the same condition at 1.2 mM and 1 mM dose, respectively (Figs. 1 and 2)

Summary

Introduction

Breast cancer is the most common cause of cancer death among women (522.000 deaths in 2012) and the most frequently diagnosed cancer in 140 of 184 countriesPLOS ONE | DOI:10.1371/journal.pone.0115287 December 22, 2014Vitamin C Effect on Mitoxantrone-Induced Cytotoxicity worldwide [1]. The use of natural dietary antioxidants to minimize cytotoxicity and tissue damage by antitumor agents is gaining consideration [17] Some natural substances, such as ascorbic acid (vitamin C or vit C), have been shown to improve the antineoplastic activity of some chemotherapeutic drugs [18]. Our results show that combined supplementations of vit C and MTZ have cytotoxic effect by apoptotic death, a mild G2/M elongation and activation of H2AX and mild PI3K pathways, and, can be really useful for improving the chemotherapy treatments on breast cancer

Methods

Results

Conclusion