Apoptosis of human Burkitt's lymphoma cells induced by 2-N,N-diethylaminocarbonyloxymethyl-1-diphenylmethyl-4-(3,4,5-trimethoxybenzoyl) piperazine hydrochloride (PMS-1077).
Piperazine is one of the heterocycles which are associated with diverse pharmacological activities. 2-N,N-Diethylaminocarbonyloxymethyl-1-diphenylmethyl-4-(3,4,5-trimethoxybenzoyl) piperazine hydrochloride (PMS-1077) is a trisubstituted piperazine which contains a trimethoxybenzene ring and a benzhydrylpiperazine fragment, both of which can induce cell proliferation regression by different mechanisms. We have therefore examined the effects of PMS-1077 on Human Burkitt's lymphoma cells (Raji). The viability of Raji cells was determined by MTT assay and also assessed by trypan blue dye exclusion method. The results demonstrate that PMS-1077 can suppress the proliferation of Raji cells in a dose- and timedependent manner, while inhibit colony formation ability of Raji cells merely in a dose-dependent manner in vitro. Meanwhile, morphological changes were observed using fluorescence microscope. Flow cytometric analysis through PI stains showed that PMS-1077 blocked the growth of Raji cells in the G(0)/G(1) period, and induced apoptosis of Raji cells after 48 h of incubation. Cell apoptosis induced by PMS-1077 was further confirmed by staining with Annexin-V FITC and PI. Preliminary study by molecular docking suggests that PMS-1077 may inhibit tubulin polymerization. More experiments are in progress in our laboratory to reveal the mode of action of PMS-1077 in the induction of apoptosis of Raji cells.
Wang
Wen-di
WD
Institute of Cancer Biology and Drug Screening, School of Life Sciences, Lanzhou University, Lanzhou, 730000, China.
Xu
Xi-ming
XM
Chen
Ying
Y
Jiang
Peng
P
Dong
Chang-zhi
CZ
Wang
Qin
Q
D017304:Annexin A5; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001665:Binding Sites / Q000187:drug effects; D002051:Burkitt Lymphoma / Q000188:drug therapy / Q000473:pathology*; D002219:Carbamates / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D010879:Piperazines / Q000494:pharmacology*; D011034:Podophyllotoxin / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism; D014410:Tumor Stem Cell Assay
C549421:2-N,N-diethylaminocarbonyloxymethyl-1-diphenylmethyl-4-(3,4,5-trimethoxybenzoyl)piperazine; D017304:Annexin A5; D000970:Antineoplastic Agents; D002219:Carbamates; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D010879:Piperazines; D014404:Tubulin; D016650:Fluorescein-5-isothiocyanate; D011034:Podophyllotoxin