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Article

Nitidine chloride inhibits proliferation, induces apoptosis via the Akt pathway and exhibits a synergistic effect with doxorubicin in ovarian cancer cells

  • Authors:
    • Feng Ding
    • Tianfeng Liu
    • Nina Yu
    • Shihong Li
    • Xiaofei Zhang
    • Guanghong Zheng
    • Chunming Lv
    • Kai Mou
    • Jia Xu
    • Bo Li
    • Surong Wang
    • Haibo Song
  • View Affiliations / Copyright

    Affiliations: Department of Gynecology and Obsterics, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China, Prenatal Diagnosis Center, Zibo Maternal and Child Health Hospital, Zibo, Shandong 255000, P.R. China, Department of Cardiology, Central Hospital of Zibo, Zibo, Shandong 255036, P.R. China
  • Pages: 2853-2859
    |
    Published online on: July 29, 2016
       https://doi.org/10.3892/mmr.2016.5577
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Abstract

Nitidine chloride (NC) exhibits anti-tumor properties in various types of tumor. However, to the best of our knowledge there is no previous evidence of NC involvement in the apoptosis or proliferation of ovarian cancer cells and the underlying molecular mechanisms. The present study aimed to investigate the influence of NC on the viability and apoptosis of ovarian cancer cells and the synergistic effect NC and doxorubicin (DOX) may have on ovarian cancer cells. The viability and proliferation of ovarian cancer cells were examined using a methyl thiazolyl tetrazolium assay and 3H-thymidine incorporation assay. The apoptotic rate of ovarian cancer cells was detected by flow cytometry. The expression of apoptosis‑associated proteins and Akt serine/threonine kinase 1 (Akt) were determined by western blot analysis following NC treatment. The inhibitory effect of NC on the proliferation of ovarian cancer cells was demonstrated in a time and dose‑dependent manner. The pro-apoptotic effect of NC on ovarian cancer cells was also observed. It was determined that NC significantly downregulated the protein expression levels of B‑cell CLL/lymphoma 2 (Bcl-2) and upregulated the expression of Bcl‑2‑associated X protein, p53, caspase‑3 and ‑9. NC suppressed Akt phosphorylation. Additionally, the present study demonstrated that the effect of NC on the proliferation and apoptosis of ovarian cancer cells was Akt‑dependent by using the phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt signaling pathway inhibitor, LY294002. NC exhibited a synergistic inhibitory effect on the viability of ovarian cancer cells when combined with DOX. The current study demonstrated that NC inhibited the proliferation and induced the apoptosis of ovarian cancer cells via the Akt signaling pathway and highlighted its potential clinical application for the treatment of ovarian cancer.
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View References

1 

Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Cohen M, Pierredon S, Wuillemin C, Delie F and Petignat P: Acellular fraction of ovarian cancer ascites induce apoptosis by activating JNK and inducing BRCA1, Fas and FasL expression in ovarian cancer cells. Oncoscience. 1:262–271. 2014. View Article : Google Scholar

4 

Sun ZL, Tang YJ, Wu WG, Xing J, He YF, Xin DM, Yu YL, Yang Y and Han P: AZD1480 can inhibit the biological behavior of ovarian cancer SKOV3 cells in vitro. Asian Pac J Cancer Prev. 14:4823–4827. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Holschneider CH and Berek JS: Ovarian cancer: Epidemiology, biology and prognostic factors. Semin Surg Oncol. 19:3–10. 2000. View Article : Google Scholar : PubMed/NCBI

6 

Vaughan S, Coward JI, Bast RC Jr, Berchuck A, Berek JS, Brenton JD, Coukos G, Crum CC, Drapkin R, Etemadmoghadam D, et al: Rethinking ovarian cancer: Recommendations for improving outcomes. Nat Reviews Cancer. 11:719–725. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Wang Z, Jiang W, Zhang Z, Qian M and Du B: Nitidine chloride inhibits LPS-induced inflammatory cytokines production via MAPK and NFkappab pathway in raw 264.7 cells. J Ethnopharmacol. 144:145–150. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Del Poeta M, Chen SF, Von Hoff D, Dykstra CC, Wani MC, Manikumar G, Heitman J, Wall ME and Perfect JR: Comparison of in vitro activities of camptothecin and nitidine derivatives against fungal and cancer cells. Antimicrob Agents Chemother. 43:2862–2868. 1999.PubMed/NCBI

9 

Fang Z, Tang Y, Jiao W, Xing Z, Guo Z, Wang W, Xu Z and Liu Z: Nitidine chloride induces apoptosis and inhibits tumor cell proliferation via suppressing ERK signaling pathway in renal cancer. Food Chem Toxicol. 66:210–216. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Chen J, Wang J, Lin L, He L, Wu Y, Zhang L, Yi Z, Chen Y, Pang X and Liu M: Inhibition of STAT3 signaling pathway by nitidine chloride suppressed the angiogenesis and growth of human gastric cancer. Mol Cancer Ther. 11:277–287. 2012. View Article : Google Scholar

11 

Liao J, Xu T, Zheng JX, Lin JM, Cai QY, Yu DB and Peng J: Nitidine chloride inhibits hepatocellular carcinoma cell growth in vivo through the suppression of the JAK1/STAT3 signaling pathway. Int J Mol Med. 32:79–84. 2013.PubMed/NCBI

12 

Sun M, Zhang N, Wang X, Cai C, Cun J, Li Y, Lv S and Yang Q: Nitidine chloride induces apoptosis, cell cycle arrest and synergistic cytotoxicity with DOX in breast cancer cells. Tumour Biol. 35:10201–10212. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Fang Z, Tang Y, Jiao W, Xing Z, Guo Z, Wang W, Shi B, Xu Z and Liu Z: Nitidine chloride inhibits renal cancer cell metastasis via suppressing AKT signaling pathway. Food Chem Toxicol. 60:246–251. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Pan X, Han H, Wang L, Yang L, Li R, Li Z, Liu J, Zhao Q, Qian M, Liu M and Du B: Nitidine chloride inhibits breast cancer cells migration and invasion by suppressing c-Src/FAK associated signaling pathway. Cancer Lett. 313:181–191. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Adams JM and Cory S: The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene. 26:1324–1337. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Cai Q, Lin J, Wei L, Zhang L, Wang L, Zhan Y, Zeng J, Xu W, Shen A, Hong Z and Peng J: Hedyotis diffusa willd inhibits colorectal cancer growth in vivo via inhibition of STAT3 signaling pathway. Int J Mol Sci. 13:6117–6128. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Surh YJ: Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer. 3:768–780. 2003. View Article : Google Scholar : PubMed/NCBI

18 

Thomasset SC, Berry DP, Garcea G, Marczylo T, Steward WP and Gescher AJ: Dietary polyphenolic phytochemicals-promising cancer chemopreventive agents in humans? A review of their clinical properties. Int J Cancer. 120:451–458. 2007. View Article : Google Scholar

19 

Zhang Y, Zhuang Z, Meng Q, Jiao Y, Xu J and Fan S: Polydatin inhibits growth of lung cancer cells by inducing apoptosis and causing cell cycle arrest. Oncology lett. 7:295–301. 2014.

20 

Reed JC: Bcl-2: Prevention of apoptosis as a mechanism of drug resistance. Hematol Oncol Clin North Am. 9:451–473. 1995.PubMed/NCBI

21 

Antonsson B: Bax and other pro-apoptotic Bcl-2 family 'killer-proteins' and their victim the mitochondrion. Cell Tissue Res. 306:347–361. 2001. View Article : Google Scholar : PubMed/NCBI

22 

Crompton M: Bax, Bid and the permeabilization of the mitochondrial outer membrane in apoptosis. Curr Opin Cell Biol. 12:414–419. 2000. View Article : Google Scholar : PubMed/NCBI

23 

Baffy G, Miyashita T, Williamson JR and Reed JC: Apoptosis induced by withdrawal of interleukin-3 (IL-3) from an IL-3-dependent hematopoietic cell line is associated with repartitioning of intracellular calcium and is blocked by enforced Bcl-2 oncoprotein production. J Biol Chem. 268:6511–6519. 1993.PubMed/NCBI

24 

Precht TA, Phelps RA, Linseman DA, Butts BD, Le SS, Laessig TA, Bouchard RJ and Heidenreich KA: The permeability transition pore triggers Bax translocation to mitochondria during neuronal apoptosis. Cell Death Differ. 12:255–265. 2005. View Article : Google Scholar : PubMed/NCBI

25 

Yu Q: Restoring p53-mediated apoptosis in cancer cells: New opportunities for cancer therapy. Drug Resist Updat. 9:19–25. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Somanath PR, Vijai J, Kichina JV, Byzova T and Kandel ES: The role of PAK-1 in activation of MAP kinase cascade and oncogenic transformation by Akt. Oncogene. 28:2365–2369. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Datta SR, Brunet A and Greenberg ME: Cellular survival: A play in three Akts. Genes Dev. 13:2905–2927. 1999. View Article : Google Scholar : PubMed/NCBI

28 

Gardai SJ, Hildeman DA, Frankel SK, Whitlock BB, Frasch SC, Borregaard N, Marrack P, Bratton DL and Henson PM: Phosphorylation of Bax Ser184 by Akt regulates its activity and apoptosis in neutrophils. J Biol Chem. 279:21085–21095. 2004. View Article : Google Scholar : PubMed/NCBI

29 

Khan KH, Blanco-Codesido M and Molife LR: Cancer therapeutics: Targeting the apoptotic pathway. Crit Rev Oncol Hematol. 90:200–219. 2014. View Article : Google Scholar : PubMed/NCBI

30 

Octavia Y, Tocchetti CG, Gabrielson KL, Janssens S, Crijns HJ and Moens AL: DOX-induced cardiomyopathy: From molecular mechanisms to therapeutic strategies. J Mol Cell Cardiol. 52:1213–1225. 2012. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Ding F, Liu T, Yu N, Li S, Zhang X, Zheng G, Lv C, Mou K, Xu J, Li B, Li B, et al: Nitidine chloride inhibits proliferation, induces apoptosis via the Akt pathway and exhibits a synergistic effect with doxorubicin in ovarian cancer cells. Mol Med Rep 14: 2853-2859, 2016.
APA
Ding, F., Liu, T., Yu, N., Li, S., Zhang, X., Zheng, G. ... Song, H. (2016). Nitidine chloride inhibits proliferation, induces apoptosis via the Akt pathway and exhibits a synergistic effect with doxorubicin in ovarian cancer cells. Molecular Medicine Reports, 14, 2853-2859. https://doi.org/10.3892/mmr.2016.5577
MLA
Ding, F., Liu, T., Yu, N., Li, S., Zhang, X., Zheng, G., Lv, C., Mou, K., Xu, J., Li, B., Wang, S., Song, H."Nitidine chloride inhibits proliferation, induces apoptosis via the Akt pathway and exhibits a synergistic effect with doxorubicin in ovarian cancer cells". Molecular Medicine Reports 14.3 (2016): 2853-2859.
Chicago
Ding, F., Liu, T., Yu, N., Li, S., Zhang, X., Zheng, G., Lv, C., Mou, K., Xu, J., Li, B., Wang, S., Song, H."Nitidine chloride inhibits proliferation, induces apoptosis via the Akt pathway and exhibits a synergistic effect with doxorubicin in ovarian cancer cells". Molecular Medicine Reports 14, no. 3 (2016): 2853-2859. https://doi.org/10.3892/mmr.2016.5577
Copy and paste a formatted citation
x
Spandidos Publications style
Ding F, Liu T, Yu N, Li S, Zhang X, Zheng G, Lv C, Mou K, Xu J, Li B, Li B, et al: Nitidine chloride inhibits proliferation, induces apoptosis via the Akt pathway and exhibits a synergistic effect with doxorubicin in ovarian cancer cells. Mol Med Rep 14: 2853-2859, 2016.
APA
Ding, F., Liu, T., Yu, N., Li, S., Zhang, X., Zheng, G. ... Song, H. (2016). Nitidine chloride inhibits proliferation, induces apoptosis via the Akt pathway and exhibits a synergistic effect with doxorubicin in ovarian cancer cells. Molecular Medicine Reports, 14, 2853-2859. https://doi.org/10.3892/mmr.2016.5577
MLA
Ding, F., Liu, T., Yu, N., Li, S., Zhang, X., Zheng, G., Lv, C., Mou, K., Xu, J., Li, B., Wang, S., Song, H."Nitidine chloride inhibits proliferation, induces apoptosis via the Akt pathway and exhibits a synergistic effect with doxorubicin in ovarian cancer cells". Molecular Medicine Reports 14.3 (2016): 2853-2859.
Chicago
Ding, F., Liu, T., Yu, N., Li, S., Zhang, X., Zheng, G., Lv, C., Mou, K., Xu, J., Li, B., Wang, S., Song, H."Nitidine chloride inhibits proliferation, induces apoptosis via the Akt pathway and exhibits a synergistic effect with doxorubicin in ovarian cancer cells". Molecular Medicine Reports 14, no. 3 (2016): 2853-2859. https://doi.org/10.3892/mmr.2016.5577
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