Photodynamic inhibitory effects of three perylenequinones on human colorectal carcinoma cell line and primate embryonic stem cell line

AIM: To investigate the photodynamic inhibitory effects of Elsinochrome A (EA), Hypocrellin A (HA) and Hypocrellin B (HB) on human colorectal carcinoma Hce-8693 cells and rhesus monkey embryonic stem R366.4 cells, via inducing a poptosis. METHODS: EA, HA and HB were extracted from metabolites of Hypomyces (Fr) Tul.Sp. R366.4 cells or Hce-8693 cells were cultured with different concentrations of EA, HA or HB respectively, irradiated and incubated with fresh medium for 2 h. Cell cycle analysis was performed by flow cytometry (FCM). Data were expressed as means +/-SD and analysis of variance and Student' t-test for individual comparisons. RESULTS: The photodynamic bioactivity of EA was first reported in this study. After irradiation for 5 min, 6 min, 10 min or 20 min, photoactivated EA at lower concentrations, which were 10(-7) Mol/L, 10(-6) Mol/L, 10(-5) Mol/L respectively, had no cytotoxic effects on R366.4 ES cells. Whereas, all of the three perylenequinones could induce apoptosis with a dose-dependent manner when Hce-8693 cells were incubated with photoactivated EA, HA and HB respectively. When Hce-8693 cells were incubated with EA at 10-6 Mol/L and irradiated 5 min, 6 min, 10 min and 20 min respectively, the rates of EA-induced apoptosis were 0, 0, 13.4% and 40.5%. While the rates of HA-induced apoptosis were 29.5%, 32.0%, 40.2% and 22.6%. And the rates of HB-induced apoptosis were 0, 0, 0 and 13.7% respectively. Meanwhile, after 10-5 Mol/L treatment, the rates of EA-induced apoptosis were 32.7%, 19.3%, 26.4% and 52.7%, the rates of HA-induced apoptosis were 47.2%, 39.1%, 45.2% and 56.6%, and the rates of HB-induced apoptosis were 0, 0, 20.0% and 13.9% respectively. CONCLUSION: EA, HA and HB have significant anti-cancer activity. The order of photodynamic. inhibitory effects on tumor cells would be approximately HA>EA>HB. The molecular mechanisms of apoptosis may not be induced by reactive oxygen species and are worth further investigation.