Secalonic acid D induced leukemia cell apoptosis and cell cycle arrest of G(1) with involvement of GSK-3beta/beta-catenin/c-Myc pathway.
The anticancer activities of secalonic acid D separated from the secondary metabolites of the mangrove endophytic fungus No. ZSU44 were investigated in this study. Secalonic acid D showed potent cytotoxicity to HL60 and K562 cells, and the IC(50) values were 0.38 and 0.43 mumol/L, respectively. Annexin V-FITC/PI assay and western blot indicated that secalonic acid D induced apoptosis in HL60 and K562 cells. In addition, secalonic acid D led to cell cycle arrest of G(1) phase related to downregulation of c-Myc. Moreover, our data indicated that downregulation of c-Myc and cell cycle arrest of G(1) phase were caused not by formation of G-quadruplex structures but by activation of GSK-3beta followed by degradation of beta-catenin.
Zhang
Jian-ye
JY
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou 510060, PR China.
Tao
Li-yang
LY
Liang
Yong-ju
YJ
Yan
Yan-yan
YY
Dai
Chun-ling
CL
Xia
Xue-kui
XK
She
Zhi-gang
ZG
Lin
Yong-cheng
YC
Fu
Li-wu
LW
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D016193:G1 Phase / Q000187:drug effects / Q000502:physiology; D038362:Glycogen Synthase Kinase 3 / Q000187:drug effects / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D018922:HL-60 Cells; D006801:Humans; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D044004:Xanthones / Q000494:pharmacology* / Q000633:toxicity; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000970:Antineoplastic Agents; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D044004:Xanthones; D051176:beta Catenin; C009218:secalonic acid; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3