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ApoG2 induces cell cycle arrest of nasopharyngeal carcinoma cells by suppressing the c-Myc signaling pathway.

Hu ZY, Sun J, Zhu XF, Yang D, Zeng YX - J Transl Med (2009)

Bottom Line: 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.This data suggested that the inhibitory effect of ApoG2 on NPC cell cycle proliferation might contribute to its use in anticancer therapy.

View Article: PubMed Central - HTML - PubMed

Affiliation: 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

ABSTRACT

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.

Conclusion: 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.

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ApoG2 and its inhibitory effect on CNE-2 cell proliferation. (A) The chemical structure of ApoG2. (B) Effect of ApoG2 on NPC cell survival. Cells were exposed to 5, 10, and 20 μM ApoG2 for 24, 48, and 72 h. Compared to control cells (treated with 0.1% DMSO), percentage of viable cells in treated samples was measured using an MTT assay (mean ± standard deviation for three experiments). (C) The inhibitory effect of ApoG2 on four NPC cell lines (HONE-1, CNE-2, CNE-1 and C666-1) was compared after 72-hr treatment. Points, average of three experiments; bars, SD.
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Figure 1: ApoG2 and its inhibitory effect on CNE-2 cell proliferation. (A) The chemical structure of ApoG2. (B) Effect of ApoG2 on NPC cell survival. Cells were exposed to 5, 10, and 20 μM ApoG2 for 24, 48, and 72 h. Compared to control cells (treated with 0.1% DMSO), percentage of viable cells in treated samples was measured using an MTT assay (mean ± standard deviation for three experiments). (C) The inhibitory effect of ApoG2 on four NPC cell lines (HONE-1, CNE-2, CNE-1 and C666-1) was compared after 72-hr treatment. Points, average of three experiments; bars, SD.

Mentions: Our previous work demonstrated that ApoG2 (Fig. 1A, the chemical structure of ApoG2) could significantly kill NPC cells and suppress the growth of NPC xenografts in nude mice. In this study, we reevaluated the antiproliferative effect of ApoG2 on CNE-2 cells using an MTT assay. We treated CNE-2 cells with 5, 10 and 20 μM ApoG2 for 24, 48 and 72 h. This treatment resulted in dose- and time-dependent inhibition of cell proliferation (Fig. 1B). At 10 and 20 μM, ApoG2 inhibited about 60% and 90% of the cell growth, respectively, at 72 h.


ApoG2 induces cell cycle arrest of nasopharyngeal carcinoma cells by suppressing the c-Myc signaling pathway.

Hu ZY, Sun J, Zhu XF, Yang D, Zeng YX - J Transl Med (2009)

ApoG2 and its inhibitory effect on CNE-2 cell proliferation. (A) The chemical structure of ApoG2. (B) Effect of ApoG2 on NPC cell survival. Cells were exposed to 5, 10, and 20 μM ApoG2 for 24, 48, and 72 h. Compared to control cells (treated with 0.1% DMSO), percentage of viable cells in treated samples was measured using an MTT assay (mean ± standard deviation for three experiments). (C) The inhibitory effect of ApoG2 on four NPC cell lines (HONE-1, CNE-2, CNE-1 and C666-1) was compared after 72-hr treatment. Points, average of three experiments; bars, SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2742515&req=5

Figure 1: ApoG2 and its inhibitory effect on CNE-2 cell proliferation. (A) The chemical structure of ApoG2. (B) Effect of ApoG2 on NPC cell survival. Cells were exposed to 5, 10, and 20 μM ApoG2 for 24, 48, and 72 h. Compared to control cells (treated with 0.1% DMSO), percentage of viable cells in treated samples was measured using an MTT assay (mean ± standard deviation for three experiments). (C) The inhibitory effect of ApoG2 on four NPC cell lines (HONE-1, CNE-2, CNE-1 and C666-1) was compared after 72-hr treatment. Points, average of three experiments; bars, SD.
Mentions: Our previous work demonstrated that ApoG2 (Fig. 1A, the chemical structure of ApoG2) could significantly kill NPC cells and suppress the growth of NPC xenografts in nude mice. In this study, we reevaluated the antiproliferative effect of ApoG2 on CNE-2 cells using an MTT assay. We treated CNE-2 cells with 5, 10 and 20 μM ApoG2 for 24, 48 and 72 h. This treatment resulted in dose- and time-dependent inhibition of cell proliferation (Fig. 1B). At 10 and 20 μM, ApoG2 inhibited about 60% and 90% of the cell growth, respectively, at 72 h.

Bottom Line: 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.This data suggested that the inhibitory effect of ApoG2 on NPC cell cycle proliferation might contribute to its use in anticancer therapy.

View Article: PubMed Central - HTML - PubMed

Affiliation: 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

ABSTRACT

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus