Cytotoxic effects of N-(3-chloro-1,4-dioxo 1,4-dihydro-naphthalen-2-yl)- benzamide on androgen-dependent and -independent prostate cancer cell lines

Background: Worldwide among men, prostate cancer ranks third in cancer occurrence and sixth in cancer mortality. A number of 1, 4-naphthoquinone derivatives have been identified that possess significant pharmacological effects associated with antitumor activities. In this study, the in vitro effects of N-(3-chloro-1,4-dioxo 1,4-dihydro-naphthalen-2-yl)-benzamide (NCDDNB) were evaluated on androgen-dependent (CWR-22) and androgen-independent (PC-3, DU-145) human prostate cancer cell lines, and on a normal bone marrow cell line (HS-5). Specifically, the in vitro activity of this compound on cell cycle regulation and apoptosis was evaluated. Materials and Methods: Established methods of cell viability, cell cycle, Western blot and apoptosis were used. Results: The effect of NCDDNB on CWR-22, PC-3, DU-145 and HS-5 cells revealed significant anti-tumor activities with IC₅₀s, of 2.5, 2.5, 6.5, and 25 μM respectively. The results of cell cycle analysis showed that NCDDNB arrested PC-3, DU-145, and CWR-22 cells in the G₁-phase of the cell cycle. The compound showed no effect on the cell cycle progression in the HS-5 bone marrow cell line. These findings were further validated using Western blot analysis. NCDDNB showed the greatest amount of apoptosis in the androgen-independent PC-3 cells in a time-dependent manner with the apoptotic apex at day 5 of treatment.