Abstract
Backgroundapogossypolone (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.ResultsWe 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.ConclusionOur 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.
Highlights
Nasopharyngeal carcinoma (NPC) is an epithelial squamous cell carcinoma endemic in Southeast Asia and parts of Mediterranean and northern Africa [1]
We previously showed that ApoG2 in particular could potently kill NPC cells and had a synergic effect with cisplatin to induce cell death [5]
MTT Assay NPC cell viability was assessed using an MTT assay based on mitochondrial conversion of MTT from soluble tetrazolium salt to an insoluble colored formazan precipitate, which was dissolved in dimethyl sulfoxide (DMSO) and quantitated using a spectrophotometer
Summary
Nasopharyngeal carcinoma (NPC) is an epithelial squamous cell carcinoma endemic in Southeast Asia and parts of Mediterranean and northern Africa [1]. Radiotherapy alone cures more than 90% of cases of stage I NPC; patients with advanced disease tend to experience therapy failure. Several groups have shown that the 5-year survival rate for concurrent chemotherapy and radiotherapy is higher than that for radiotherapy alone in patients with advanced disease [2,3]. Cisplatin combined with 5-fluorouracil is the first-line chemotherapeutic regimen for NPC. This regimen has manageable toxic effects and has yielded response rates ranging from 65% to 75% [4], an urgent need for inpa-. We previously showed that ApoG2 in particular could potently kill NPC cells and had a synergic effect with cisplatin to induce cell death [5]. We further investigated the effect of ApoG2 on cell cycle regulator proteins and cell cycle progression
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
