ApoG2 induces cell cycle arrest of nasopharyngeal carcinoma cells by suppressing the c-Myc signaling pathway.
BACKGROUND
apogossypolone (ApoG2) is a novel derivate of gossypol. We previously have reported that ApoG2 is a promising compound that kills nasopharyngeal carcinoma (NPC) cells by inhibiting the antiapoptotic function of Bcl-2 proteins. However, some researchers demonstrate that the antiproliferative effect of gossypol on breast cancer cells is mediated by induction of cell cycle arrest. So this study was aimed to investigate the effect of ApoG2 on cell cycle proliferation in NPC cells.


RESULTS
We found that ApoG2 significantly suppressed the expression of c-Myc in NPC cells and induced arrest at the DNA synthesis (S) phase in a large percentage of NPC cells. Immunoblot analysis showed that expression of c-Myc protein was significantly downregulated by ApoG2 and that the expression of c-Myc's downstream molecules cyclin D1 and cyclin E were inhibited whereas p21 was induced. To further identify the cause-effect relationship between the suppression of c-Myc signaling pathway and induction of cell cycle arrest, the expression of c-Myc was interfered by siRNA. The results of cell cycle analysis showed that the downregulation of c-Myc signaling pathway by siRNA interference could cause a significant arrest of NPC cell at S phase of the cell cycle. In CNE-2 xenografts, ApoG2 significantly downregulated the expression of c-Myc and suppressed tumor growth in vivo.


CONCLUSIONS
Our findings indicated that ApoG2 could potently disturb the proliferation of NPC cells by suppressing c-Myc signaling pathway. This data suggested that the inhibitory effect of ApoG2 on NPC cell cycle proliferation might contribute to its use in anticancer therapy.
Hu
Zhe-Yu
ZY
State Key Laboratory of Oncology in South China and Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, PR China. huzheyu24@gmail.com
Sun
Jian
J
Zhu
Xiao-Feng
XF
Yang
Dajun
D
Zeng
Yi-Xin
YX
D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D006072:Gossypol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D015394:Molecular Structure; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D009368:Neoplasm Transplantation; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D014183:Transplantation, Heterologous
D050759:Cyclin-Dependent Kinase Inhibitor p21; D016271:Proto-Oncogene Proteins c-myc; C534401:apogossypolone; D006072:Gossypol
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