Vanadium compounds induce stronger growth suppression in PTEN-deficient prostate cancer cells by ROS-mediated mechanism

doi:10.5246/jcps.2017.06.047

Abstract

Abstract:

In the present study, we investigated the antiproliferative effect and the underlying mechanism of three antidiabetic vanadium compounds, metavanadate, VO(acac)₂ and VO(ma)₂, in human prostate cancer cells (PC-3 and DU-145). The results showed that vanadium compounds caused cell cycle arrest at G2/M phase evidenced by the elevation of phosphorylated Cdc2 at tyr-15. Moreover, the results revealed that vanadium compounds induced reactive oxygen species (ROS) elevation in the two cell lines. The decreased level of Cdc25C could be rescued by the antioxidant, N-acetylcysteine, indicating that vanadium compounds-induced G2/M arrest was mediated by ROS. Additionally, the three vanadium compounds exerted more potent growth inhibitory effect on PC-3 cells which are PTEN-deficient and with higher level of basal ROS. It suggested that PTEN protein might serve as a biomarker for the selectivity of antitumor therapy using ROS-generating agents. Since the studied vanadium compounds have been shown the antidiabetic activities in the previous studies, there may be additional benefits in the potential application of vanadium compounds to suppress the growth of prostate cancer cells.

Key words: Vanadium compounds, Reactive oxygen species, PTEN, Prostate cancer, Diabetes

CLC Number:

R962.1

Supporting:

Yihua Hong, Tongtong Liu, Yanjun Liu, Jingxuan Wu, Xiaogai Yang. Vanadium compounds induce stronger growth suppression in PTEN-deficient prostate cancer cells by ROS-mediated mechanism[J]. Journal of Chinese Pharmaceutical Sciences, 2017, 26(6): 432-439.

References

[1] Siegel, R.; Ward, E.; Brawley, O.; Jemal, A. CA Cancer J. Clin. 2011, 61, 212–236.

[2] Siegel, R.L.; Miller, K.D.; Jemal, A. CA Cancer J. Clin. 2015, 65, 5–29.

[3] Kintzel, P.E.; Chase, S.L.; Schultz, L.M.; O’Rourke, T.J. Pharmacotherapy. 2008, 28, 1511–1522.

[4] Bishayee, A.; Waghray, A.; Patel, M.A.; Chatterjee, M. Cancer Lett. 2010, 294, 1–12.

[5] Rehder, D. Future Med. Chem. 2016, 8, 325–338.

[6] Wu, J.X.; Hong, Y.H.; Yang, X.G. J. Biol. Inorg. Chem. 2016, 21, 919–929.

[7] Liu, T.T.; Liu, Y.J.; Wang, Q.; Yang, X.G.; Wang, K. J. Biol. Inorg. Chem. 2012, 17, 311–320.

[8] Wang, Q.; Liu, T.T.; Fu, Y.; Wang, K.; Yang, X.G. J. Biol. Inorg. Chem. 2010, 15, 1087–1097.

[9] Trachootham, D.; Alexandre, J.; Huang, P. Nat. Rev. Drug Discov. 2009, 8, 579–591.

[10] Nogueira, V.; Hay, N. Clin. Cancer Res. 2013, 19, 4309–4314.

[11] Fang, J.; Ding, M.; Yang, L.; Liu, L.Z.; Jiang, B.H. Cellular Signalling. 2007, 19, 2487–2497.

[12] Aressy, B.; Ducommun, B. Anti-Cancer Agents Med. Chem. 2008, 8, 818–824.

[13] Liu, T.T.; Liu, Y.J.; Yang, X.G. J. Chin. Pharm. Sci. 2012, 21, 57–61.

[14] Burhans, W.C.; Heintz, N.H. Free Radic. Biol. Med. 2009, 47, 1282–1293.

[15] Nogueira, V.; Park, Y.; Chen, C.C.; Xu, P.Z.; Chen, M.L.; Tonic, I.; Unterman, T.; Hay, N. Cancer Cell. 2008, 14, 458–470.

[16] Mcmenamin, M.E.; Soung, P.; Perera, S.; Kaplan, I.; Loda, M.; Sellers, W.R. Cancer Res. 1999, 59, 4291–4296.

[17] Huang, H.; Cheville, J.C.; Pan, Y.Q.; Roche, P.C.; Schmidt, L.J.; Tindall, D.J. J. Biol. Chem. 2001, 276, 38830–38836.

[18] Khandrika, L.; Kumar, B.; Koul, S.; Maroni, P.; Koul, H.K. Cancer Lett. 2009, 282, 125–136.

[19] Hua, F.; Yu, J.J.; Hu, Z.W. Cancer Lett. 2016, 374, 54–61.

[20] Kasper, J.S.; Giovannucci, E. Cancer Epidemiol. Biomarkers Prev. 2006, 15, 2056–2062.
[21] Abdollah, F.; Briganti, A.; Suardi, N.; Gallina, A.; Capitanio, U.; Salonia, A.; Cestari, A.; Guazzoni, G.; Rigatti, P.; Montorsi, F. Prostate Cancer Prostatic Dis. 2011, 14, 74–78.