Chalcones enhance TRAIL-induced apoptosis in prostate cancer cells

Abstract

Chalcones exhibit chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a naturally occurring anticancer agent that induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effect of five chalcones in combination with TRAIL on prostate cancer cells. The cytotoxicity was evaluated by the MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC. Our study showed that all five tested chalcones: chalcone, licochalcone-A, isobavachalcone, xanthohumol, butein markedly augmented TRAIL-mediated apoptosis and cytotoxicity in prostate cancer cells and confirmed the significant role of chalcones in chemoprevention of prostate cancer.

Keywords: TRAIL (tumor necrosis factor-related apoptosis-inducing ligand); apoptosis; chalcones; chemoprevention; prostate cancer.

Figure 1.

Chemical structures of the studied chalcones.

Figure 2.

Cytotoxic and apoptotic effects of chalcones on LNCaP prostate cancer cells. The cancer cells were incubated for 48 hours with five chalcones: chalcone, licochalcone-A, isobavachalcone, xanthohumol and butein at the concentrations of 20 μM and 50 μM. The values represent mean ± SD of three independent experiments performed in quadruplicate (n = 12) for cytototoxicity, or in duplicate (n = 6) for apoptosis (p < 0.05). (A) Cytotoxic activity of chalcones in LNCaP cells. The percentage of cell death was measured by MTT cytotoxicity assay. (B) Chalcone-induced apoptosis in LNCaP cells. Detection of apoptotic cell death by annexin V-FITC staining using flow cytometry.

Figure 3.

Cytotoxic and apoptotic effect of TRAIL on LNCaP prostate cancer cells. The cancer cells were incubated for 48 hours with TRAIL at the concentrations of 20–200 ng/mL. The values represent mean ± SD of three independent experiments performed in quadruplicate (n = 12) for cytototoxicity, or in duplicate (n = 6) for apoptosis (p < 0.05). (A) Cytotoxic activity of TRAIL in LNCaP cells. The percentage of cell death was measured by MTT cytotoxicity assay. (B) TRAIL-induced apoptosis in LNCaP cells. Detection of apoptotic cell death by annexin V-FITC staining using flow cytometry.

Figure 4.

Cytotoxic activity of TRAIL in combination with chalcones in LNCaP prostate cancer cells. The cancer cells were incubated for 48 hours with TRAIL at the concentrations of 20–100 ng/mL and chalcones: (A) chalcone, (B) licochalcone-A, (C) isobavachalcone, (D) xanthohumol and (E) butein at the at the concentrations of 20 μM and 50 μM. The percentage of cell death was measured by MTT cytotoxicity assay. The values represent mean ± SD of three independent experiments performed in quadruplicate (n = 12) (p < 0.05).

Figure 5.

TRAIL induced apoptosis in combination with chalcones in LNCaP prostate cancer cells. The cancer cells were incubated for 48 hours with TRAIL at the concentrations of 50 ng/ml and 100 ng/mL and chalcones: (A) chalcone, (B) licochalcone-A, (C) isobavachalcone, (D) xanthohumol and (E) butein at the concentrations of 20 μM and 50 μM. Detection of apoptotic cell death by annexin V-FITC staining using flow cytometry. The values represent mean ± SD of three independent experiments performed in duplicate (n = 6) (p < 0.05).