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. 2015 Jul 27:9:3899-909.
doi: 10.2147/DDDT.S87662. eCollection 2015.

Zinc supplementation induces apoptosis and enhances antitumor efficacy of docetaxel in non-small-cell lung cancer

Hilal Kocdor  1 , Halil Ates  2 , Suleyman Aydin  3 , Ruksan Cehreli  2 , Firat Soyarat  4 , Pinar Kemanli  4 , Duygu Harmanci  4 , Hakan Cengiz  4 , Mehmet Ali Kocdor  5
Affiliations

Zinc supplementation induces apoptosis and enhances antitumor efficacy of docetaxel in non-small-cell lung cancer

Hilal Kocdor et al. Drug Des Devel Ther. .

Abstract

Background: Exposure to exogenous zinc results in increased apoptosis, growth inhibition, and altered oxidative stress in cancer cells. Previous studies also suggested that zinc sensitizes some cancer cells to cytotoxic agents depending on the p53 status. Therefore, zinc supplementation may show anticancer efficacy solely and may increase docetaxel-induced cytotoxicity in non-small-cell lung cancer cells.

Methods: Here, we report the effects of several concentrations of zinc combined with docetaxel on p53-wild-type (A549) and p53-null (H1299) cells. We evaluated cellular viability, apoptosis, and cell cycle progression as well as oxidative stress parameters, including superoxide dismutase, glutathione peroxidase, and malondialdehyde levels.

Results: Zinc reduced the viability of A549 cells and increased the apoptotic response in both cell lines in a dose-dependent manner. Zinc also amplified the docetaxel effects and reduced its inhibitory concentration 50 (IC50) values. The superoxide dismutase levels increased in all treatment groups; however, glutathione peroxidase was slightly increased in the combination treatments. Zinc also caused malondialdehyde elevations at 50 μM and 100 μM.

Conclusion: Zinc has anticancer efficacy against non-small-cell lung cancer cells in the presence of functionally active p53 and enhances docetaxel efficacy in both p53-wild-type and p53-deficient cancer cells.

Keywords: A549; H1299; docetaxel; lung cancer; zinc.

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Figures

Figure 1
Figure 1
(A) IC50 values of A549 and H1299 cell lines for docetaxel and zinc. (B) 50 μM and 100 μM zinc pretreatment reduced docetaxel-induced IC50 values in both cell lines.
Figure 2
Figure 2
Growth inhibitory effects of zinc, docetaxel and combinations. In the graphics, horizontal lines indicate statistical significance between the groups (P<0.05, ANOVA followed by Holm–Sidak). Bar abbreviations from left, C: Control, Doc: docetaxel, Zinc: zinc 50 (50 μM), zinc 100, zinc-IC50 groups, respectively; combinations Doc + Zinc 50, Doc + Zinc 100, and Doc + Zinc IC50.
Figure 2
Figure 2
Growth inhibitory effects of zinc, docetaxel and combinations. In the graphics, horizontal lines indicate statistical significance between the groups (P<0.05, ANOVA followed by Holm–Sidak). Bar abbreviations from left, C: Control, Doc: docetaxel, Zinc: zinc 50 (50 μM), zinc 100, zinc-IC50 groups, respectively; combinations Doc + Zinc 50, Doc + Zinc 100, and Doc + Zinc IC50.
Figure 3
Figure 3
Cell cycle analysis of the study groups.
See this image and copyright information in PMC

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