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Combination of metformin and paclitaxel suppresses proliferation and induces apoptosis of human prostate cancer cells via oxidative stress and targeting the mitochondria‑dependent pathway

  • Authors:
    • Yuwan Zhao
    • Xin Zeng
    • Huancheng Tang
    • Dongcai Ye
    • Jianjun Liu
  • View Affiliations / Copyright

    Affiliations: Laboratory of Urology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China
    Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4277-4284
    |
    Published online on: March 6, 2019
       https://doi.org/10.3892/ol.2019.10119
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Abstract

Previous studies have reported that metformin (MET) has anticancer activity. In combination with chemotherapeutic drugs, MET reduces the dosage of chemotherapeutic drugs required and enhances anticancer efficacy. In the present study, the combination of MET and paclitaxel (PTX) in three human prostate cancer (PCa) cell lines (22RV1, PC‑3 and LNCaP) was evaluated to investigate the effects on proliferation and apoptosis of PCa cells. The present study explored whether their effects were associated with reactive oxygen species (ROS). An MTT assay and microscopy were used to study the effect of MET + PTX on cell growth. Half maximal inhibitory concentration (IC50) values were obtained for MET (12.281±1.089 mM for 22RV1, 2.248±0.352 mM for PC‑3 cells and 3.610±0.577 mM for LNCaP cells) and PTX (13.170±1.12 nM for PC‑3 cells) at 48 h. Since the survival rate of 22RV1 and LNCaP cells did not decrease linearly with increasing PTX concentration, it is difficult to estimate accurate IC50; therefore, only IC50 values for PTX in PC‑3 cells were given. When treating the cells with 5 mM MET, the IC50 of PTX decreased to 5.423±0.734 nM for PC‑3 cells. Annexin V and propidium iodide staining was used to investigate apoptosis by flow cytometry. The apoptotic mechanisms of MET + PTX in PCa were investigated by detecting the expression of apoptosis‑related proteins, activities of caspase‑3/7, intracellular ROS accumulation, mitochondrial membrane potential, and intracellular levels of adenosine 5'‑triphosphate (ATP). MET + PTX induced PCa apoptosis and ROS accumulation, and decreased mitochondrial membrane potential and intracellular levels of ATP. Taken together, these results indicated that MET + PTX suppressed PCa cell proliferation in a dose‑ and time‑dependent manner. In addition, MET + PTX induced apoptosis by increasing ROS levels, reducing mitochondrial membrane potential, and activating mitochondrial‑dependent apoptotic pathways.
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1 

Yang Y and Wu XH: Study on the influence of metformin on castration-resistant prostate cancer PC-3 cell line biological behavior by its inhibition on PLCε gene-mediated Notch1/Hes and androgen receptor signaling pathway. Eur Rev Med Pharmacol Sci. 21:1918–1923. 2017.PubMed/NCBI

2 

Crawford ED: Epidemiology of prostate cancer. Urology. 62:3–12. 2003. View Article : Google Scholar : PubMed/NCBI

3 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Sandblom G and Varenhorst E: Incidence rate and management of prostate carcinoma. Biomed Pharmacother. 55:135–143. 2001. View Article : Google Scholar : PubMed/NCBI

5 

Zitzmann S, Mier W, Schad A, Kinscherf R, Askoxylakis V, Kramer S, Altmann A, Eisenhut M and Haberkorn U: A new prostate carcinoma binding peptide (DUP-1) for tumor imaging and therapy. Clin Cancer Res. 11:139–146. 2005.PubMed/NCBI

6 

Chi K, Hotte SJ, Joshua AM, North S, Wyatt AW, Collins LL and Saad F: Treatment of mCRPC in the AR-axis-targeted therapy-resistant state. Ann Oncol. 26:2044–2056. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Weaver BA: How Taxol/paclitacel kills cancer cells. Mol Biol Cell. 25:2677–2681. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Sobue S, Mizutani N, Aoyama Y, Kawamoto Y, Suzuki M, Nozawa Y, Ichihara M and Murate T: Mechanism of paclitaxel resistance in a human prostate cancer cell line, PC3-PR, and its sensitization by cabazitaxel. Biochem Biophys Res Commun. 479:808–813. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Yang Y, Ma Y, Sheng J, Huang Y, Zhao Y, Fang W, Hong S, Tian Y, Xue C and Zhang L: A multicenter, retrospective epidemiologic survey of the clinical features and management of bone metastatic disease in China. Chin J Cancer. 35:402016. View Article : Google Scholar : PubMed/NCBI

10 

Hatoum D and McGowan EM: Recent advances in the use of metformin: Can treating diabetes prevent breast cancer? Biomed Res Int. 2015:5484362015. View Article : Google Scholar : PubMed/NCBI

11 

Dowling RJ, Goodwin PJ and Stambolic V: Understanding the benefit of metformin use in cancer treatment. BMC Med. 9:332011. View Article : Google Scholar : PubMed/NCBI

12 

Gou S, Cui P, Li X, Shi P, Liu T and Wang C: Low concentrations of metformin selectively inhibit CD133+ cell proliferation in pancreatic cancer and have anticancer action. PLoS One. 8:e639692013. View Article : Google Scholar : PubMed/NCBI

13 

Noto H, Goto A, Tsujimoto T and Noda M: Cancer risk in diabetic patients treated with metformin: A systematic review and meta-analysis. PLoS One. 7:e334112012. View Article : Google Scholar : PubMed/NCBI

14 

Pollak MN: Investigating metformin for cancer prevention and treatment: The end of the beginning. Cancer Discov. 2:778–790. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Del Barco S, Vazquez-Martin A, Cufí S, Oliveras-Ferraros C, Bosch-Barrera J, Joven J, Martin-Castillo B and Menendez JA: Metformin: Multi-faceted protection against cancer. Oncotarget. 2:896–917. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Zakikhani M, Dowling R, Fantus IG, Sonenberg N and Pollak M: metformin Is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res. 66:10269–10273. 2006. View Article : Google Scholar : PubMed/NCBI

17 

Goodwin PJ, Ligibel JA and Stambolic V: Metformin in breast cancer: Time for action. J Clin Oncol. 27:3271–3273. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Wang LW, Li ZS, Zou DW, Jin ZD, Gao J and Xu GM: metformin induces apoptosis of pancreatic cancer cells. World J Gastroenterol. 14:7192–7198. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Shank JJ, Yang K, Ghannam J, Cabrera L, Johnston CJ, Reynolds RK and Buckanovich RJ: Metformin targets ovarian cancer stem cells in vitro and in vivo. Gynecol Oncol. 127:390–397. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Iliopoulos D, Hirsch HA and Struhl K: Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types. Cancer Res. 71:3196–3201. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Abedi H, Aghaei M, Panjehpour M and Hajiahmadi S: Mitochondrial and caspase pathways are involved in the induction of apoptosis by IB-MECA in ovarian cancer cell lines. Tumor Biol. 35:11027–11039. 2014. View Article : Google Scholar

22 

Cheng G and Lanza-Jacoby S: Metformin decreases growth of pancreatic cancer cells by decreasing reactive oxygen species: Role of NOX4. Biochem Biophys Res Commun. 465:41–46. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Ding H, Han C, Guo D, Chin YW, Ding Y, Kinghorn AD and D'Ambrosio SM: Selective induction of apoptosis of human oral cancer cell lines by avocado extracts via a ROS-mediated mechanism. Nutr Cancer. 61:348–356. 2009. View Article : Google Scholar : PubMed/NCBI

24 

Khandrika L, Kumar B, Koul S, Maroni P and Koul HK: Role of Oxidative Stress in Prostate Cancer. Cancer Lett. 282:125–136. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Harley ME, Allan LA, Sanderson HS and Clarke PR: Phosphorylation of Mcl-1 by CDK1-cyclin B1 initiates its Cdc20-dependent destruction during mitotic arrest. EMBO J. 29:2407–2420. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Castilla C, Flores ML, Medina R, Perez-Valderrama B, Romero F, Tortolero M, Japón MA and Sáez C: Prostate cancer cell response to paclitaxel is affected by abnormally expressed securin PTTG1. Mol Cancer Ther. 13:2372–2383. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Tudor G, Aguilera A, Halverson DO, Laing ND and Sausville EA: Susceptibility to drug-induced apoptosis correlates with differential modulation of Bad, Bcl-2 and Bcl-xL protein levels. Cell Death Differ. 7:574–586. 2000. View Article : Google Scholar : PubMed/NCBI

28 

Lim SJ, Choi MK, Kim MJ and Kim JK: Alpha-tocopheryl succinate potentiates the paclitaxel-induced apoptosis through enforced caspase 8 activation in human H460 lung cancer cells. Exp Mol Med. 41:737–745. 2009. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhao Y, Zeng X, Tang H, Ye D and Liu J: Combination of metformin and paclitaxel suppresses proliferation and induces apoptosis of human prostate cancer cells via oxidative stress and targeting the mitochondria‑dependent pathway. Oncol Lett 17: 4277-4284, 2019.
APA
Zhao, Y., Zeng, X., Tang, H., Ye, D., & Liu, J. (2019). Combination of metformin and paclitaxel suppresses proliferation and induces apoptosis of human prostate cancer cells via oxidative stress and targeting the mitochondria‑dependent pathway. Oncology Letters, 17, 4277-4284. https://doi.org/10.3892/ol.2019.10119
MLA
Zhao, Y., Zeng, X., Tang, H., Ye, D., Liu, J."Combination of metformin and paclitaxel suppresses proliferation and induces apoptosis of human prostate cancer cells via oxidative stress and targeting the mitochondria‑dependent pathway". Oncology Letters 17.5 (2019): 4277-4284.
Chicago
Zhao, Y., Zeng, X., Tang, H., Ye, D., Liu, J."Combination of metformin and paclitaxel suppresses proliferation and induces apoptosis of human prostate cancer cells via oxidative stress and targeting the mitochondria‑dependent pathway". Oncology Letters 17, no. 5 (2019): 4277-4284. https://doi.org/10.3892/ol.2019.10119
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao Y, Zeng X, Tang H, Ye D and Liu J: Combination of metformin and paclitaxel suppresses proliferation and induces apoptosis of human prostate cancer cells via oxidative stress and targeting the mitochondria‑dependent pathway. Oncol Lett 17: 4277-4284, 2019.
APA
Zhao, Y., Zeng, X., Tang, H., Ye, D., & Liu, J. (2019). Combination of metformin and paclitaxel suppresses proliferation and induces apoptosis of human prostate cancer cells via oxidative stress and targeting the mitochondria‑dependent pathway. Oncology Letters, 17, 4277-4284. https://doi.org/10.3892/ol.2019.10119
MLA
Zhao, Y., Zeng, X., Tang, H., Ye, D., Liu, J."Combination of metformin and paclitaxel suppresses proliferation and induces apoptosis of human prostate cancer cells via oxidative stress and targeting the mitochondria‑dependent pathway". Oncology Letters 17.5 (2019): 4277-4284.
Chicago
Zhao, Y., Zeng, X., Tang, H., Ye, D., Liu, J."Combination of metformin and paclitaxel suppresses proliferation and induces apoptosis of human prostate cancer cells via oxidative stress and targeting the mitochondria‑dependent pathway". Oncology Letters 17, no. 5 (2019): 4277-4284. https://doi.org/10.3892/ol.2019.10119
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