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


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.


CONCLUSIONS
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.
Ma
Lan
L
Graduate School of the Chinese Acedemy of Sciencees, Beijing 100871, China. wji@mail.kiz.ac.cn
Tai
Hong
H
Li
Cong
C
Zhang
Yu
Y
Wang
Ze-Hua
ZH
Ji
Wei-Zhi
WZ
D000818:Animals; D002277:Carcinoma / Q000188:drug therapy*; D002460:Cell Line; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004622:Embryo, Mammalian; D006801:Humans; D008253:Macaca mulatta; D010569:Perylene / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D019800:Phenol; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011809:Quinones / Q000627:therapeutic use*; D013234:Stem Cells / Q000187:drug effects*
D017319:Photosensitizing Agents; D011809:Quinones; C062775:elsinochrome A; D019800:Phenol; D010569:Perylene; C048388:hypocrellin A; C064522:hypocrellin B