Original ContributionSafe and targeted anticancer efficacy of a novel class of antioxidant-conjugated difluorodiarylidenyl piperidones: Differential cytotoxicity in healthy and cancer cells
Section snippets
Chemicals
Superoxide dismutase (SOD), 6-carboxy-2′,7′-dichlorodihydrofluorescein diacetate, diacetoxymethyl ester (H2DCF-DA), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and antibodies against actin were obtained from Sigma (St. Louis, MO, USA). 5-Diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide (DEPMPO) was from Radical Vision (Jerome-Marseille, France). Cell culture medium (RPMI 1640), fetal bovine serum (FBS), antibiotics, sodium pyruvate, trypsin, and phosphate-buffered saline
Cytotoxicity of DAPs to cancer cells
The cytotoxicity of DAPs (H-4073, HO-3867, H-4318, HO-4200) to established human cancer cell lines, namely A27820, A2780R, MCF-7, HCT-116, PC-3, HepG2, A549, and SCC4, was evaluated by exposing the cells to 10 μM concentration of the compounds for 24 h. All four compounds induced a substantial loss of cell viability in all the human cancer cell lines tested (Fig. 1). In particular, H-4073 and H-4318 exhibited higher toxicity compared to HO-3867 or HO-4200. The results further indicated that the
Discussion
The development of smart anticancer agents that selectively destroy cancer cells while sparing the surrounding healthy tissues/cells is the main goal of cancer therapy. The results of this study show that all four DAPs induce potential cytotoxicity in cancer cells. The N-hydroxypyrroline-conjugated DAPs, HO-3867 and HO-4200, although equally toxic to cancer cells, are significantly less toxic to noncancerous (healthy) cells. The differential cytotoxicity is mediated through inhibition of STAT3
Acknowledgments
This work was supported by National Institutes of Health Grant CA102264 (P.K.), a Kaleidoscope of Hope Foundation grant (K.S.), and Hungarian Research Fund Grant OTKA K81123 (K.H.).
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