Down regulation of differentiated embryonic chondrocytes 1 (DEC1) is involved in 8-methoxypsoralen-induced apoptosis in HepG2 cells.
8-Methoxypsoralen (8-MOP), a naturally occurring compound, is a potent modulator of epidermal cell growth and differentiation in combination with ultraviolet light. However, there is little information on 8-MOP contribution to cell apoptosis alone. In the study, we evaluated 8-MOP, independently of its photoactivation, induced apoptosis in human hepatocellular carcinoma HepG2 cells. And we provide a molecular explanation linking 8-MOP to induce apoptosis. In HepG2 cells, treatment with 8-MOP induced the cell apoptosis in both dose-dependent and time-dependent manners. IC(50) values of 8-MOP were 8.775, 5.398 μM for 48 and 72 h, respectively. Further study showed that 8-MOP decreased the procaspase-3, procaspase-8, and procaspase-9, increased the ratio of Bax/Bcl-2 and decreased the survivin. Moreover, 8-MOP decreased differentiated embryonic chondrocyte gene1 (DEC1). Overexpression of DEC1 antagonized partially apoptosis induced by 8-MOP. And overexpression of DEC1 abolished the decrease of survivin and the activation of caspase-3 induced by 8-MOP partially. So, down regulation of DEC1 is involved in 8-MOP-induced apoptosis in HepG2 cells. Here, it is demonstrated that DEC1 possesses anti-apoptotic effects in 8-MOP-treated HepG2 cells. The findings provide more of a basis for 8-MOP as an anti-tumor agent in cancer therapy.
Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Yan
Y
Peng
Wei
W
Liu
Jing
J
Xiong
Hai Yan
HY
Gui
Xue Min
XM
Feng
Rui Ni
RN
Chen
Gang
G
Hu
Jian
J
Yang
D017209:Apoptosis / Q000187:drug effects; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D056945:Hep G2 Cells; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008730:Methoxsalen / Q000008:administration & dosage / Q000494:pharmacology*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology; D000077022:Survivin; D013997:Time Factors
D051792:Basic Helix-Loop-Helix Proteins; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D018398:Homeodomain Proteins; D051034:Inhibitor of Apoptosis Proteins; D008730:Methoxsalen; D017319:Photosensitizing Agents; D000077022:Survivin; C107989:BHLHE40 protein, human; C107489:BIRC5 protein, human