Effects of isocamptothecin, a novel camptothecin analogue, on proliferation, apoptosis and telomerase activity in HaCaT cells.
Camptothecin is a topoisomerase I inhibitor with definite anti-psoriatic effect. As it is limited in clinical application because of serious side effects and toxicity, many researchers are striving hard to develop derivatives or analogues of camptothecin with higher effects and less toxicity. To explore the anti-psoriatic potential of isocamptothecin, a novel camptothecin analogue, its effects on proliferation, apoptosis and telomerase activity were investigated in the human keratinocyte cell line HaCaT. Incubation with isocamptothecin resulted in a time- and concentration-dependent inhibition of HaCaT cell proliferation. However, isocamptothecin showed larger inhibitory concentration at 50% than camptothecin, suggesting far less cytotoxicity. In addition, isocamptothecin induced apoptosis in a concentration-dependent manner and induced typical morphologic features of apoptosis in HaCaT cells. Moreover, isocamptothecin downregulated the telomerase activity of HaCaT cells not only at concentrations of apoptosis induction but also at concentration insufficient to induce apoptosis, providing additional mechanisms that further account for its ability to inhibit keratinocytes proliferation and induce apoptosis. These results indicate that isocamptothecin possesses similar effects on keratinocytes with camptothecin, but shows far less cytotoxicity, it may probably become a promising agent for psoriasis therapy.
Lin
Jingrong
J
Department of Dermatology, the first affiliated hospital of Dalian Medical University, Dalian, China.
Liu
Xiaoming
X
Bao
Yongming
Y
Hou
Suchun
S
An
Lijia
L
Lin
Xiran
X
D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects*; D029769:Camptotheca / Q000737:chemistry; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D004247:DNA / Q000032:analysis; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006131:Growth Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007536:Isomerism; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D016133:Polymerase Chain Reaction; D011565:Psoriasis / Q000188:drug therapy; D019098:Telomerase / Q000187:drug effects* / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles
D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D013778:Tetrazolium Salts; D013844:Thiazoles; C530145:isocamptothecin A; C530146:isocamptothecin B; D004247:DNA; D019098:Telomerase; C022616:thiazolyl blue; D002166:Camptothecin