The role of individual caspases in cell death induction by taxanes in breast cancer cells

Cancer Cell International

Jan Kovář¹  Iwao Ojima²  Ilaria Zanardi²  Jitka Stančíková¹  Jan Šrámek¹  Vlasta Němcová-Fürstová¹  Martina Schmiedlová¹  Kamila Balušíková¹  Michael Jelínek¹ 

[1] Department of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague, Czech Republic;Institute of Chemical Biology and Drug Discovery, State University of New York at Stony Brook, Stony Brook, NY, USA

关键词: Cell death;    Caspases;    Breast cancer;    Taxanes;   

Others  :  1171062
DOI  :  10.1186/s12935-015-0155-7

 received in 2014-01-29, accepted in 2014-12-31,  发布年份 2015

【 摘 要 】

Background

In previous study we showed that caspase-2 plays the role of an apical caspase in cell death induction by taxanes in breast cancer cells. This study deals with the role of other caspases. We tested breast cancer cell lines SK-BR-3 (functional caspase-3) and MCF-7 (nonfunctional caspase-3).

Methods and results

Using western blot analysis we demonstrated the activation of initiator caspase-8 and -9 as well as executioner caspase-6 and -7 in both tested cell lines after application of taxanes (paclitaxel, SB-T-1216) at death-inducing concentrations. Caspase-3 activation was also found in SK-BR-3 cells. Employing specific siRNAs after taxane application, suppression of caspase-3 expression significantly increased the number of surviving SK-BR-3 cells. Inhibition of caspase-7 expression also increased the number of surviving SK-BR-3 and MCF-7 cells. On the other hand, suppression of caspase-8 and caspase-9 expression had no significant effect on cell survival. However, caspase-9 seemed to be involved in the activation of caspase-3 and caspase-7. Caspase-3 and caspase-7 appeared to activate mutually. Furthermore, we observed a significant decrease in mitochondrial membrane potential (flow cytometric analysis) and cytochrome c release (confocal microscopy, western blot after cell fractionation) from mitochondria in SK-BR-3 cells. No such changes were observed in MCF-7 cells after taxane treatment.

Conclusion

We conclude that the activation of apical caspase-2 results in the activation of caspase-3 and -7 without the involvement of mitochondria. Caspase-9 can be activated directly via caspase-2 or alternatively after cytochrome c release from mitochondria. Subsequently, caspase-9 activation can also lead to caspase-3 and -7 activations. Caspase-3 and caspase-7 activate mutually. It seems that there is also a parallel pathway involving mitochondria that can cooperate in taxane-induced cell death in breast cancer cells.

【 授权许可】

   
2015 Jelínek et al.; licensee BioMed Central.

【 图 表 】

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【 参考文献 】

• [1]Bedard PL, Di Leo A, Piccart-Gebhart MJ: Taxanes: optimizing adjutant chemotherapy for early-stage breast cancer. Nat Rev Clin Oncol 2010, 7:22-36.
• [2]Ojima I, Slater JC, Michaud E, Kuduk SD, Bounaud PY, Vrignaud P, et al.: Syntheses and structure-activity relationships of the second-generation antitumor taxoids: exceptional activity against drug-resistant cancer cells. J Med Chem 1996, 39:3889-96.
• [3]Ferlini C, Raspaglio G, Mozzetti S, Cicchillitti L, Filippetti F, Gallo D, et al.: The seco-taxane IDN5390 is able to target class III beta-tubulin and to overcome paclitaxel resistance. Cancer Res 2005, 65:2397-405.
• [4]Galletti E, Magnani M, Renzulli ML, Botta M: Paclitaxel and docetaxel resistance: molecular mechanisms and development of new generation taxanes. Chem Med Chem 2007, 2:920-42.
• [5]Ehrlichová M, Koc M, Truksa J, Naďová Z, Václavíková R, Kovář J: Cell death induced by taxanes in breast cancer cells: cytochrome C is released in resistant but not in sensitive cells. Anticancer Res 2005, 25:4215-24.
• [6]Ojima I, Chen J, Sun L, Borella CP, Wang T, Miller ML, et al.: Design, synthesis, and biological evaluation of new-generation taxoids. J Med Chem 2008, 51:3203-21.
• [7]Orr GA, Verdier-Pinard P, McDaid H, Horwitz SB: Mechanisms of Taxol resistance related to microtubules. Oncogene 2003, 22:7280-95.
• [8]Xiao H, Verdier-Pinard P, Fernandez-Fuentes N, Burd B, Angeletti R, Fiser A, et al.: Insights into the mechanism of microtubule stabilization by Taxol. Proc Natl Acad Sci U S A 2006, 103:10166-73.
• [9]Yuan SY, Hsu SL, Tsai KJ, Yang CR: Involvement of mitochondrial pathway in Taxol-induced apoptosis of human T24 bladder cancer cells. Urol Res 2002, 30:282-8.
• [10]Morse DL, Gray H, Payne CM, Gillies RJ: Docetaxel induces cell death through mitotic catastrophe in human breast cancer cells. Mol Cancer Ther 2005, 4:1495-504.
• [11]Mediavilla-Varela M, Pacheco FJ, Almaguel F, Perez J, Sahakian E, Daniels TR, et al.: Docetaxel-induced prostate cancer cell death involves concomitant activation of caspase and lysosomal pathways and is attenuated by LEDGF/p75. Mol Cancer 2009, 8:68. BioMed Central Full Text
• [12]Vobořilová J, Němcová-Fürstová V, Neubauerová J, Ojima I, Zanardi I, Gut I, et al.: Cell death induced by novel fluorinated taxanes in drug-sensitive and drug-resistant cancer cells. Invest New Drugs 2011, 29:411-23.
• [13]Mhaidat NM, Wang Y, Kejda KA, Zhang XD, Hersey P: Docetaxel-induced apoptosis in melanoma cells is dependent on activation of caspase-2. Mol Cancer Ther 2007, 6:752-61.
• [14]Kovář J, Ehrlichová M, Smejkalová B, Zanardi I, Ojima I, Gut I: Comparison of cell death-inducing effect of novel taxane SB-T-1216 and paclitaxel in breast cancer cells. Anticancer Res 2009, 29:2951-60.
• [15]von Haefen C, Wieder T, Essmann F, Schulze-Osthoff K, Dörken B, Daniel PT: Paclitaxel-induced apoptosis in BJAB cells proceeds via a death receptor-independent, caspases-3/-8-driven mitochondrial amplification loop. Oncogene 2003, 22:2236-47.
• [16]Liao PC, Tan SK, Lieu CH, Jung HK: Involvement of endoplasmic reticulum in paclitaxel-induced apoptosis. J Cell Biochem 2008, 104:1509-23.
• [17]Park SJ, Wu CH, Gordon JD, Zhong X, Emami A, Safa AR: Taxol induces caspase-10-dependent apoptosis. J Biol Chem 2004, 279:51057-67.
• [18]Zhivotovsky B, Orrenius S: Caspase-2 function in response to DNA damage. Biochem Biophys Res Commun 2005, 331:859-67.
• [19]Tinel A, Janssens S, Lippens S, Cuenin S, Logette E, Jaccard B, et al.: Autoproteolysis of PIDD marks the bifurcation between pro-death caspase-2 and pro-survival NF-kappaB pathway. EMBO J 2007, 26:197-208.
• [20]Jelínek M, Balušíková K, Kopperová D, Němcová-Fürstová V, Šrámek J, Fiedlerová J, et al.: Caspase-2 is involved in cell death induction by taxanes in breast cancer cells. Cancer Cell Int 2013, 13:42. BioMed Central Full Text
• [21]Ho LH, Read SH, Dorstyn L, Lambrusco L, Kumar S: Caspase-2 is required for cell death induced by cytoskeletal disruption. Oncogene 2008, 27:3393-404.
• [22]Wang YF, Chen CY, Chung SF, Chiou YH, Lo HR: Involvement of oxidative stress and caspase activation in paclitaxel-induced apoptosis of primary effusion lymphoma cells. Cancer Chemother Pharmacol 2004, 54:322-30.
• [23]Janssen K, Pohlmann S, Jänicke RU, Schulze-Osthoff K, Fischer U: Apaf-1 and caspase-9 deficiency prevents apoptosis in a Bax-controlled pathway and promotes clonogenic survival during paclitaxel treatment. Blood 2007, 110:3662-72.
• [24]Drago-Ferrante R, Santulli A, Di Fjord R, Giuliano M, Calvaruso G, Tesoriere G, et al.: Low doses of paclitaxel potently induce apoptosis in human retinoblastoma Y79 cells by up-regulating E2F1. Int J Oncol 2008, 33:677-87.
• [25]André N, Carré M, Brasseur G, Pourroy B, Kovacic H, Briand C, et al.: Paclitaxel targets mitochondria upstream of caspase activation in intact human neuroblastoma cells. FEBS Lett 2002, 532:256-60.
• [26]Luo Y, Ling Y, Guo W, Pang J, Liu W, Fang Y, et al.: Docetaxel loaded oleic acid-coated hydroxyapatite nanoparticles enhance the docetaxel-induced apoptosis through activation of caspase-2 in androgen independent prostate cancer cells. J Control Release 2010, 147:278-88.
• [27]Mhaidat NM, Zhang XD, Jiang CC, Hersey P: Docetaxel-induced apoptosis of human melanoma is mediated by activation of c-Jun NH2-terminal kinase and inhibited by the mitogen-activated protein kinase extracellular signal-regulated kinase 1/2 pathway. Clin Cancer Res 2007, 13:1308-14.
• [28]Kim JY, Chung JY, Lee SG, Kim YJ, Park JE, Yoo KS, et al.: Nuclear interaction of Smac/DIABLO with Survivin at G2/M arrest prompts docetaxel-induced apoptosis in DU145 prostate cancer cells. Biochem Biophys Res Commun 2006, 350:949-54.
• [29]Chadderton A, Villeneuve DJ, Gluck S, Kirwan-Rhude AF, Gannon BR, Blair DE, et al.: Role of specific apoptotic pathways in the restoration of paclitaxel-induced apoptosis by valspodar in doxorubicin-resistant MCF-7 breast cancer cells. Breast Cancer Res Treat 2000, 59:231-44.
• [30]Flores ML, Castilla C, Ávila R, Ruiz-Borrego M, Sáez C, Japón MA: Paclitaxel sensitivity of breast cancer cells requires efficient mitotic arrest and disruption of Bcl-xL/Bak interaction. Breast Cancer Res Treat 2012, 133:917-28.
• [31]Sarkar S, Mazumdar A, Dash R, Sarkar D, Fisher PB, Mandal M: ZD6474 enhances paclitaxel antiproliferative and apoptotic effects in breast carcinoma cells. J Cell Physiol 2011, 226:375-84.
• [32]Friedrich K, Wieder T, Von Haefen C, Radetzki S, Jänicke R, Schulze-Osthoff K, et al.: Overexpression of caspase-3 restores sensitivity for drug-induced apoptosis in breast cancer cell lines with acquired drug resistance. Oncogene 2001, 20:2749-60.
• [33]Perchellet EM, Crow KR, Gakhar G, Nguyen TA, Shi A, Hua DH, et al.: Bioactivity and molecular targets of novel substituted quinolines in murine and human tumor cell lines in vitro. Int J Oncol 2010, 36:673-88.
• [34]Li Y, Xing D, Chen Q: Dynamic monitoring of apoptosis in chemotherapies with multiple fluorescence reporters. Mol Imaging Biol 2009, 11:213-22.
• [35]Yang YI, Lee KT, Park HJ, Kim TJ, Choi YS, Shih IM, et al.: Tectorigenin sensitizes paclitaxel-resistant human ovarian cancer cells through downregulation of the Akt and NFκB pathway. Carcinogenesis 2012, 33:2488-98.
• [36]Ofir R, Seidman R, Rabinski T, Krup M, Yavelsky V, Weinstein Y, et al.: Taxol induced apoptosis in human SKOV3 ovarian and MCF7 breast carcinoma cells is caspase-3 and caspase-9 independent. Cell Death Differ 2002, 9:636-42.
• [37]Mao HL, Liu PS, Zheng JF, Zhang PH, Zhou LG, Xin G, et al.: Transfection of Smac/DIABLO sensitizes drug-resistant tumor cells to TRAIL or paclitaxel-induced apoptosis in vitro. Pharmacol Res 2007, 56:483-92.
• [38]Fabbri F, Amadori D, Carloni S, Brigliadori G, Tesei A, Ulivi P, et al.: Mitotic catastrophe and apoptosis induced by docetaxel in hormone-refractory prostate cancer cells. J Cell Physiol 2008, 217:494-501.
• [39]Almubarak H, Jones A, Chaisuparat R, Zhang M, Meiller TF, Scheper MA: Zoledronic acid directly suppresses cell proliferation and induces apoptosis in highly tumorigenic prostate and breast cancers. J Carcinog 2011, 10:2.
• [40]Ajabnoor GM, Crook T, Coley HM: Paclitaxel resistance is associated with switch from apoptotic to autophagic cell death in MCF-7 breast cancer cells. Cell Death Dis 2012, 3:260.
• [41]Brentnall M, Rodriguez-Menocal L, De Guevara RL, Cepero E, Boise LH: Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis. BMC Cell Biol 2013, 14:32. BioMed Central Full Text
• [42]Musílková J, Kovář J: Additive stimulatory effect of extracellular calcium and potassium on non-transferrin ferric iron uptake by HeLa and K562 cells. Biochim Biophys Acta 2001, 1514:117-26.
• [43]Koc M, Nad’ová Z, Truksa J, Ehrlichová M, Kovář J: Iron deprivation induces apoptosis via mitochondrial changes related to Bax translocation. Apoptosis 2005, 10:381-93.