Docetaxel induces Bcl-2- and pro-apoptotic caspase-independent death of human prostate cancer DU145 cells

Ogura,Takeharu; Tanaka,Yoshiyuki; Tamaki,Hiroki; Harada,Mamoru

doi:10.3892/ijo.2016.3482

Docetaxel induces Bcl-2- and pro-apoptotic caspase-independent death of human prostate cancer DU145 cells

Authors:
- Takeharu Ogura
- Yoshiyuki Tanaka
- Hiroki Tamaki
- Mamoru Harada
View Affiliations

Affiliations: Biological Research Department, Sawai Pharmaceutical Co., Ltd., Osaka, Japan, Department of Pharmacy, Shimane University Hospital, Shimane, Japan, Department of Immunology, Shimane University Faculty of Medicine, Shimane, Japan
Published online on: April 8, 2016 https://doi.org/10.3892/ijo.2016.3482
Pages: 2330-2338
Copyright: © Ogura et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Docetaxel is a useful chemotherapeutic agent for the first-line treatment of hormone-refractory prostate cancer. Abnormal expression of Bcl-2 is commonly found in cancer cells, which increases their anti-apoptotic potency and chemoresistance. We investigated the effects of Bcl-2 expression status on the susceptibility of DU145 cells, an androgen-independent human prostate cancer cell line, to docetaxel and other anticancer agents. A panel of Bcl-2-expressing DU145 cell lines was established. Bcl-2 expression levels were unrelated to the susceptibility of DU145 cells to docetaxel. The sensitivity of DU145 cells to cisplatin fluctuated, and the sensitivity to tumor necrosis factor (TNF)-α was decreased by Bcl-2 overexpression. In a xenograft mouse model, overexpression of Bcl-2 drastically decreased the sensitivity of DU145 cells to cisplatin and TNF-α; however, there was no change in the response to docetaxel. Fluorescent microscopy revealed that Bcl-2-overexpression had no effect on the docetaxel-induced death of DU145 cells, but significantly decreased DU145 cell death induced by cisplatin or TNF-α. Interestingly, docetaxel hardly induced caspase-3/7 activation in control or Bcl-2-overexpressing DU145 cells, but did at a low level in LNCaP cells, another prostate cancer cell line. Moreover, in contrast to LNCaP cells, the reduced viabilities of docetaxel-treated control and Bcl-2-overexpressing DU145 cells were not restored by the addition of either a Bid inhibitor or a panel of pro-apoptotic caspase inhibitors. These findings indicate that the antitumor effects of docetaxel on DU145 cells are independent of both Bcl-2 and pro-apoptotic caspases.

View Figures

View References

1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Siegel R, Ward E, Brawley O and Jemal A: Cancer statistics, 2011: The impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 61:212–236. 2011. View Article : Google Scholar : PubMed/NCBI
3	Morgentaler A: Testosterone and prostate cancer: An historical perspective on a modern myth. Eur Urol. 50:935–939. 2006. View Article : Google Scholar : PubMed/NCBI
4	Huggins C and Hodges CV: Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. 1941. CA Cancer J Clin. 22:232–240. 1972. View Article : Google Scholar : PubMed/NCBI
5	Miyamoto H, Messing EM and Chang C: Androgen deprivation therapy for prostate cancer: Current status and future prospects. Prostate. 61:332–353. 2004. View Article : Google Scholar : PubMed/NCBI
6	Hammerer P and Madersbacher S: Landmarks in hormonal therapy for prostate cancer. BJU Int. 110(Suppl 1): 23–29. 2012. View Article : Google Scholar : PubMed/NCBI
7	Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Théodore C, James ND, Turesson I, et al: Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 351:1502–1512. 2004. View Article : Google Scholar : PubMed/NCBI
8	Petrylak DP, Tangen CM, Hussain MHA, Lara PNJ Jr, Jones JA, Taplin ME, Burch PA, Berry D, Moinpour C, Kohli M, et al: Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 351:1513–1520. 2004. View Article : Google Scholar : PubMed/NCBI
9	Sinibaldi VJ: Docetaxel treatment in the elderly patient with hormone refractory prostate cancer. Clin Interv Aging. 2:555–560. 2007.
10	Merseburger AS, Bellmunt J, Jenkins C, Parker C and Fitzpatrick JM; European Treatment Practices Group. Perspectives on treatment of metastatic castration-resistant prostate cancer. Oncologist. 18:558–567. 2013. View Article : Google Scholar : PubMed/NCBI
11	Sweeney CJ and Chamberlain D: Insights into E3805: The CHAARTED trial. Future Oncol. 11:897–899. 2015. View Article : Google Scholar : PubMed/NCBI
12	Fulda S and Debatin K-M: Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene. 25:4798–4811. 2006. View Article : Google Scholar : PubMed/NCBI
13	Pienta KJ: Preclinical mechanisms of action of docetaxel and docetaxel combinations in prostate cancer. Semin Oncol. 28(Suppl 15): 3–7. 2001. View Article : Google Scholar : PubMed/NCBI
14	Stein CA: Mechanisms of action of taxanes in prostate cancer. Semin Oncol. 26(Suppl 17): 3–7. 1999.PubMed/NCBI
15	Ganansia-Leymarie V, Bischoff P, Bergerat J-P and Holl V: Signal transduction pathways of taxanes-induced apoptosis. Curr Med Chem Anticancer Agents. 3:291–306. 2003. View Article : Google Scholar : PubMed/NCBI
16	Noguchi K, Shakuto S, Sakairi T and Yoshida Y: Decrease in prostate specific antigen secretion correlated with docetaxel-induced growth inhibition and apoptosis in human prostate tumor cells. Gan To Kagaku Ryoho. 36:1863–1870. 2009.PubMed/NCBI
17	Green DR: Apoptotic pathways: Paper wraps stone blunts scissors. Cell. 102:1–4. 2000. View Article : Google Scholar : PubMed/NCBI
18	Kuwana T, Smith JJ, Muzio M, Dixit V, Newmeyer DD and Kornbluth S: Apoptosis induction by caspase-8 is amplified through the mitochondrial release of cytochrome c. J Biol Chem. 273:16589–16594. 1998. View Article : Google Scholar : PubMed/NCBI
19	Green DR: Apoptotic pathways: The roads to ruin. Cell. 94:695–698. 1998. View Article : Google Scholar : PubMed/NCBI
20	Scaffidi C, Fulda S, Srinivasan A, Friesen C, Li F, Tomaselli KJ, Debatin KM, Krammer PH and Peter ME: Two CD95 (APO-1/ Fas) signaling pathways. EMBO J. 17:1675–1687. 1998. View Article : Google Scholar : PubMed/NCBI
21	Luo X, Budihardjo I, Zou H, Slaughter C and Wang X: Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell. 94:481–490. 1998. View Article : Google Scholar : PubMed/NCBI
22	Li H, Zhu H, Xu CJ and Yuan J: Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell. 94:491–501. 1998. View Article : Google Scholar : PubMed/NCBI
23	Gross A, McDonnell JM and Korsmeyer SJ: BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 13:1899–1911. 1999. View Article : Google Scholar : PubMed/NCBI
24	Yip KW and Reed JC: Bcl-2 family proteins and cancer. Oncogene. 27:6398–6406. 2008. View Article : Google Scholar : PubMed/NCBI
25	Johnson MI, Robinson MC, Marsh C, Robson CN, Neal DE and Hamdy FC: Expression of Bcl-2, Bax, and p53 in high-grade prostatic intraepithelial neoplasia and localized prostate cancer: Relationship with apoptosis and proliferation. Prostate. 37:223–229. 1998. View Article : Google Scholar : PubMed/NCBI
26	Bubendorf L, Sauter G, Moch H, Jordan P, Blöchlinger A, Gasser TC and Mihatsch MJ: Prognostic significance of Bcl-2 in clinically localized prostate cancer. Am J Pathol. 148:1557–1565. 1996.PubMed/NCBI
27	Brown JM and Wilson G: Apoptosis genes and resistance to cancer therapy: What does the experimental and clinical data tell us? Cancer Biol Ther. 2:477–490. 2003. View Article : Google Scholar : PubMed/NCBI
28	Srivastava RK, Sasaki CY, Hardwick JM and Longo DL: Bcl-2-mediated drug resistance: Inhibition of apoptosis by blocking nuclear factor of activated T lymphocytes (NFAT)-induced Fas ligand transcription. J Exp Med. 190:253–265. 1999. View Article : Google Scholar : PubMed/NCBI
29	Inoue Y, Gika M, Abiko T, Oyama T, Saitoh Y, Yamazaki H, Nakamura M, Abe Y, Kawamura M and Kobayashi K: Bcl-2 overexpression enhances in vitro sensitivity against docetaxel in non-small cell lung cancer. Oncol Rep. 13:259–264. 2005.PubMed/NCBI
30	Losert D, Pratscher B, Soutschek J, Geick A, Vornlocher H-P, Müller M and Wacheck V: Bcl-2 downregulation sensitizes nonsmall cell lung cancer cells to cisplatin, but not to docetaxel. Anticancer Drugs. 18:755–761. 2007. View Article : Google Scholar : PubMed/NCBI
31	Noguchi S: Predictive factors for response to docetaxel in human breast cancers. Cancer Sci. 97:813–820. 2006. View Article : Google Scholar : PubMed/NCBI
32	Liu C, Zhu Y, Lou W, Nadiminty N, Chen X, Zhou Q, Shi XB, deVere White RW and Gao AC: Functional p53 determines docetaxel sensitivity in prostate cancer cells. Prostate. 73:418–427. 2013. View Article : Google Scholar
33	Gurova KV, Rokhlin OW, Budanov AV, Burdelya LG, Chumakov PM, Cohen MB and Gudkov AV: Cooperation of two mutant p53 alleles contributes to Fas resistance of prostate carcinoma cells. Cancer Res. 63:2905–2912. 2003.PubMed/NCBI
34	Tamaki H, Harashima N, Hiraki M, Arichi N, Nishimura N, Shiina H, Naora K and Harada M: Bcl-2 family inhibition sensitizes human prostate cancer cells to docetaxel and promotes unexpected apoptosis under caspase-9 inhibition. Oncotarget. 5:11399–11412. 2014. View Article : Google Scholar : PubMed/NCBI
35	Mediavilla-Varela M, Pacheco FJ, Almaguel F, Perez J, Sahakian E, Daniels TR, Leoh LS, Padilla A, Wall NR, Lilly MB, et al: Docetaxel-induced prostate cancer cell death involves concomitant activation of caspase and lysosomal pathways and is attenuated by LEDGF/p75. Mol Cancer. 8:682009. View Article : Google Scholar : PubMed/NCBI
36	Chwieralski CE, Welte T and Bühling F: Cathepsin-regulated apoptosis. Apoptosis. 11:143–149. 2006. View Article : Google Scholar : PubMed/NCBI
37	Delavallée L, Cabon L, Galán-Malo P, Lorenzo HK and Susin SA: AIF-mediated caspase-independent necroptosis: A new chance for targeted therapeutics. IUBMB Life. 63:221–232. 2011. View Article : Google Scholar : PubMed/NCBI
38	Yang ZJ, Chee CE, Huang S and Sinicrope FA: The role of autophagy in cancer: Therapeutic implications. Mol Cancer Ther. 10:1533–1541. 2011. View Article : Google Scholar : PubMed/NCBI
39	Liao P-C, Tan S-K, Lieu C-H and Jung H-K: Involvement of endoplasmic reticulum in paclitaxel-induced apoptosis. J Cell Biochem. 104:1509–1523. 2008. View Article : Google Scholar : PubMed/NCBI
40	Jang M-S, Lee S-J, Kang NS and Kim E: Cooperative phosphorylation of FADD by Aur-A and Plk1 in response to taxol triggers both apoptotic and necrotic cell death. Cancer Res. 71:7207–7215. 2011. View Article : Google Scholar : PubMed/NCBI
41	Kumar Biswas S, Huang J, Persaud S and Basu A: Down-regulation of Bcl-2 is associated with cisplatin resistance in human small cell lung cancer H69 cells. Mol Cancer Ther. 3:327–334. 2004.PubMed/NCBI
42	Savry A, Carre M, Berges R, Rovini A, Pobel I, Chacon C, Braguer D and Bourgarel-Rey V: Bcl-2-enhanced efficacy of microtubule-targeting chemotherapy through Bim overexpression: Implications for cancer treatment. Neoplasia. 15:49–60. 2013. View Article : Google Scholar : PubMed/NCBI