Skip to main content
Top
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

Inhibition of autophagy enhances the cytotoxic effect of PA-MSHA in breast cancer

Authors: Wen-Huan Xu, Zhe-Bin Liu, Yi-Feng Hou, Qi Hong, Da-Li Hu, Zhi-Ming Shao

Published in: BMC Cancer | Issue 1/2014

Login to get access

Abstract

Background

PA-MSHA, a genetically engineered Pseudomonas aeruginosa (PA) strain, is currently under investigation as a new anti-cancer drug. It can induce cell cycle arrest and apoptosis in different human cancer cells, including hormone receptor negative breast cancer cells. However, the underlying mechanism of tumor lethality mediated by PA-MSHA remains to be fully investigated.

Methods

The effect of PA-MSHA on human hormone receptor negative breast cancer cells was analyzed by morphological measurement, western blot, cell proliferation assay and mouse xenograft model.

Results

PA-MSHA was found to induce endoplasmic reticulum (ER) stress in breast cancer cell lines through the IRE1 signaling pathway. Inhibiting autophagy potentiated the cytotoxic effect of PA-MSHA while treating breast cancer cell lines. In mouse xenograft model, PA-MSHA produced more pronounced tumor suppression in mice inoculated with IRE1 gene knockdown. MDA-MB-231HM cells.

Conclusions

These findings demonstrated inhibiting autophagy together with PA-MSHA might be a promising therapeutic strategy in treating hormone receptor negative breast cancer cells.
Appendix
Available only for authorised users
Literature
1.
go back to reference Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D: Molecular portraits of human breast tumors. Nature. 2000, 406: 747-752. 10.1038/35021093.CrossRefPubMed Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D: Molecular portraits of human breast tumors. Nature. 2000, 406: 747-752. 10.1038/35021093.CrossRefPubMed
2.
go back to reference Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Lønning PE, Børresen-Dale AL: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001, 98: 10869-10874. 10.1073/pnas.191367098.CrossRefPubMedPubMedCentral Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Lønning PE, Børresen-Dale AL: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001, 98: 10869-10874. 10.1073/pnas.191367098.CrossRefPubMedPubMedCentral
3.
go back to reference Li Z, Hao D, Zhang H, Ren L, Yang Y, Li L, Chai J, Zhou X, Fu L: A clinical study of PA-MSHA vaccine used for adjuvant therapy of lymphoma and lung cancer. Hua Xi Yi Ke Da Xue Xue Bao. 2000, 15: 334-337. Li Z, Hao D, Zhang H, Ren L, Yang Y, Li L, Chai J, Zhou X, Fu L: A clinical study of PA-MSHA vaccine used for adjuvant therapy of lymphoma and lung cancer. Hua Xi Yi Ke Da Xue Xue Bao. 2000, 15: 334-337.
4.
go back to reference Liu ZB, Hou YF, Min-Dong Di GH, Wu J, Shen ZZ, Shao ZM: PA-MSHA inhibits proliferation and induces apoptosis through the up-regulation and activation of caspases in the human breast cancer cell lines. J Cell Biochem. 2009, 108: 195-206. 10.1002/jcb.22241.CrossRefPubMed Liu ZB, Hou YF, Min-Dong Di GH, Wu J, Shen ZZ, Shao ZM: PA-MSHA inhibits proliferation and induces apoptosis through the up-regulation and activation of caspases in the human breast cancer cell lines. J Cell Biochem. 2009, 108: 195-206. 10.1002/jcb.22241.CrossRefPubMed
5.
go back to reference Cao Z, Shi L, Li Y, Wang J, Wang D, Wang G, Sun B, Mu L, Yang M, Li H: Pseudomonas aeruginosa: mannose sensitive hemagglutinin inhibits the growth of human hepatocarcinoma cells via mannose-mediated apoptosis. Dig Dis Sci. 2009, 54: 2118-2127. 10.1007/s10620-008-0603-5.CrossRefPubMed Cao Z, Shi L, Li Y, Wang J, Wang D, Wang G, Sun B, Mu L, Yang M, Li H: Pseudomonas aeruginosa: mannose sensitive hemagglutinin inhibits the growth of human hepatocarcinoma cells via mannose-mediated apoptosis. Dig Dis Sci. 2009, 54: 2118-2127. 10.1007/s10620-008-0603-5.CrossRefPubMed
6.
go back to reference Boyce M, Yuan J: Cellular response to endoplasmic reticulum stress: a matter of life or death. Cell Death Differ. 2006, 13: 363-373. 10.1038/sj.cdd.4401817.CrossRefPubMed Boyce M, Yuan J: Cellular response to endoplasmic reticulum stress: a matter of life or death. Cell Death Differ. 2006, 13: 363-373. 10.1038/sj.cdd.4401817.CrossRefPubMed
7.
8.
go back to reference Bernales S, Papa FR, Walter P: Intracellular signaling by the unfolded protein response. Annu Rev Cell Dev Biol. 2006, 22: 487-508. 10.1146/annurev.cellbio.21.122303.120200.CrossRefPubMed Bernales S, Papa FR, Walter P: Intracellular signaling by the unfolded protein response. Annu Rev Cell Dev Biol. 2006, 22: 487-508. 10.1146/annurev.cellbio.21.122303.120200.CrossRefPubMed
9.
go back to reference Momoi T: Conformational diseases and ER stress-mediated cell death: apoptotic cell death and autophagic cell death. Curr Mol Med. 2006, 6: 111-118. 10.2174/156652406775574596.CrossRefPubMed Momoi T: Conformational diseases and ER stress-mediated cell death: apoptotic cell death and autophagic cell death. Curr Mol Med. 2006, 6: 111-118. 10.2174/156652406775574596.CrossRefPubMed
10.
go back to reference Criollo A, Maiuri MC, Tasdemir E, Vitale I, Fiebig AA, Andrews D, Molgó J, Díaz J, Lavandero S, Harper F, Pierron G, di Stefano D, Rizzuto R, Szabadkai G, Kroemer G: Regulation of autophagy by the inositol trisphosphate receptor. Cell Death Differ. 2007, 14: 1029-1039.PubMed Criollo A, Maiuri MC, Tasdemir E, Vitale I, Fiebig AA, Andrews D, Molgó J, Díaz J, Lavandero S, Harper F, Pierron G, di Stefano D, Rizzuto R, Szabadkai G, Kroemer G: Regulation of autophagy by the inositol trisphosphate receptor. Cell Death Differ. 2007, 14: 1029-1039.PubMed
11.
go back to reference Ding WX, Ni HM, Gao W, Hou YF, Melan MA, Chen X, Stolz DB, Shao ZM, Yin XM: Differential effects of endoplasmic reticulum stress-induced autophagy on cell survival. J Biol Chem. 2007, 282: 4702-4710. 10.1074/jbc.M609267200.CrossRefPubMed Ding WX, Ni HM, Gao W, Hou YF, Melan MA, Chen X, Stolz DB, Shao ZM, Yin XM: Differential effects of endoplasmic reticulum stress-induced autophagy on cell survival. J Biol Chem. 2007, 282: 4702-4710. 10.1074/jbc.M609267200.CrossRefPubMed
12.
go back to reference Høyer-Hansen M, Bastholm L, Szyniarowski P, Campanella M, Szabadkai G, Farkas T, Bianchi K, Fehrenbacher N, Elling F, Rizzuto R, Mathiasen IS, Jäättelä M: Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-b, and Bcl-2. Mol Cell. 2007, 25: 193-205. 10.1016/j.molcel.2006.12.009.CrossRefPubMed Høyer-Hansen M, Bastholm L, Szyniarowski P, Campanella M, Szabadkai G, Farkas T, Bianchi K, Fehrenbacher N, Elling F, Rizzuto R, Mathiasen IS, Jäättelä M: Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-b, and Bcl-2. Mol Cell. 2007, 25: 193-205. 10.1016/j.molcel.2006.12.009.CrossRefPubMed
13.
go back to reference Levine B, Klionsky DJ: Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell. 2004, 6: 463-477. 10.1016/S1534-5807(04)00099-1.CrossRefPubMed Levine B, Klionsky DJ: Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell. 2004, 6: 463-477. 10.1016/S1534-5807(04)00099-1.CrossRefPubMed
14.
go back to reference Kondo Y, Kanzawa T, Sawaya R, Kondo S: The role of autophagy in cancer development and response to therapy. Nat Rev Cancer. 2005, 5: 726-734. 10.1038/nrc1692.CrossRefPubMed Kondo Y, Kanzawa T, Sawaya R, Kondo S: The role of autophagy in cancer development and response to therapy. Nat Rev Cancer. 2005, 5: 726-734. 10.1038/nrc1692.CrossRefPubMed
15.
go back to reference Li JY, Ou ZL, Yu SJ, Gu XL, Yang C, Chen AX, Di GH, Shen ZZ, Shao ZM: The chemokine receptor CCR4 promotes tumor growth and lung metastasis in breast cancer. Breast Cancer Res Treat. 2012, 131: 837-848. 10.1007/s10549-011-1502-6.CrossRefPubMed Li JY, Ou ZL, Yu SJ, Gu XL, Yang C, Chen AX, Di GH, Shen ZZ, Shao ZM: The chemokine receptor CCR4 promotes tumor growth and lung metastasis in breast cancer. Breast Cancer Res Treat. 2012, 131: 837-848. 10.1007/s10549-011-1502-6.CrossRefPubMed
16.
go back to reference Watkins SC, Cullen MJ: A qualitative and quantitative study of the ultrastructure of regenerating muscle fibres in Duchenne muscular dystrophy and polymyositis. J Neurol Sci. 1987, 82: 181-192. 10.1016/0022-510X(87)90017-7.CrossRefPubMed Watkins SC, Cullen MJ: A qualitative and quantitative study of the ultrastructure of regenerating muscle fibres in Duchenne muscular dystrophy and polymyositis. J Neurol Sci. 1987, 82: 181-192. 10.1016/0022-510X(87)90017-7.CrossRefPubMed
17.
go back to reference Wang JS, Wang FB, Zhang QG, Shen ZZ, Shao ZM: Enhanced expression of Rab27A gene by breast cancer cells promoting invasiveness and the metastasis potential by secretion of insulin-like growth factor-II. Mol Cancer Res. 2008, 6: 372-382. 10.1158/1541-7786.MCR-07-0162.CrossRefPubMed Wang JS, Wang FB, Zhang QG, Shen ZZ, Shao ZM: Enhanced expression of Rab27A gene by breast cancer cells promoting invasiveness and the metastasis potential by secretion of insulin-like growth factor-II. Mol Cancer Res. 2008, 6: 372-382. 10.1158/1541-7786.MCR-07-0162.CrossRefPubMed
18.
go back to reference Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T: LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 2000, 19: 5720-5728. 10.1093/emboj/19.21.5720.CrossRefPubMedPubMedCentral Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T: LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 2000, 19: 5720-5728. 10.1093/emboj/19.21.5720.CrossRefPubMedPubMedCentral
19.
go back to reference Tasdemir E, Galluzzi L, Maiuri MC, Criollo A, Vitale I, Hangen E, Modjtahedi N, Kroemer G: Methods for assessing autophagy and autophagic cell death. Methods Mol Biol. 2008, 445: 29-76. 10.1007/978-1-59745-157-4_3.CrossRefPubMed Tasdemir E, Galluzzi L, Maiuri MC, Criollo A, Vitale I, Hangen E, Modjtahedi N, Kroemer G: Methods for assessing autophagy and autophagic cell death. Methods Mol Biol. 2008, 445: 29-76. 10.1007/978-1-59745-157-4_3.CrossRefPubMed
20.
go back to reference Mu XY: Success in establishing the MSHA-positive Pseudomonas aeruginosa fimbrial strain. Wei Sheng Wu Xue Bao. 1986, 26: 176-179.PubMed Mu XY: Success in establishing the MSHA-positive Pseudomonas aeruginosa fimbrial strain. Wei Sheng Wu Xue Bao. 1986, 26: 176-179.PubMed
21.
go back to reference Sun WL, Chen J, Wang YP, Zheng H: Autophagy protects breast cancer cells from epirubicin-induced apoptosis and facilitates epirubicin-resistance development. Autophagy. 2011, 7: 1035-1044. 10.4161/auto.7.9.16521.CrossRefPubMed Sun WL, Chen J, Wang YP, Zheng H: Autophagy protects breast cancer cells from epirubicin-induced apoptosis and facilitates epirubicin-resistance development. Autophagy. 2011, 7: 1035-1044. 10.4161/auto.7.9.16521.CrossRefPubMed
22.
go back to reference Bellodi C, Lidonnici MR, Hamilton A, Helgason GV, Soliera AR, Ronchetti M, Galavotti S, Young KW, Selmi T, Yacobi R, Van Etten RA, Donato N, Hunter A, Dinsdale D, Tirrò E, Vigneri P, Nicotera P, Dyer MJ, Holyoake T, Salomoni P, Calabretta B: Targeting autophagy potentiates tyrosine kinase inhibitor-induced cell death in Philadelphia chromosome-positive cells, including primary CML stem cells. J Clin Invest. 2009, 119: 1109-1123. 10.1172/JCI35660.CrossRefPubMedPubMedCentral Bellodi C, Lidonnici MR, Hamilton A, Helgason GV, Soliera AR, Ronchetti M, Galavotti S, Young KW, Selmi T, Yacobi R, Van Etten RA, Donato N, Hunter A, Dinsdale D, Tirrò E, Vigneri P, Nicotera P, Dyer MJ, Holyoake T, Salomoni P, Calabretta B: Targeting autophagy potentiates tyrosine kinase inhibitor-induced cell death in Philadelphia chromosome-positive cells, including primary CML stem cells. J Clin Invest. 2009, 119: 1109-1123. 10.1172/JCI35660.CrossRefPubMedPubMedCentral
23.
go back to reference Ramakrishnan S, Nguyen TM, Subramanian IV, Kelekar A: Autophagy and angiogenesis inhibition. Autophagy. 2007, 3: 512-515.CrossRefPubMed Ramakrishnan S, Nguyen TM, Subramanian IV, Kelekar A: Autophagy and angiogenesis inhibition. Autophagy. 2007, 3: 512-515.CrossRefPubMed
24.
go back to reference Harding HP, Calfon M, Urano F, Novoa I, Ron D: Transcriptional and translational control in the Mammalian unfolded protein response. Annu Rev Cell Dev Biol. 2002, 18: 575-799. 10.1146/annurev.cellbio.18.011402.160624.CrossRefPubMed Harding HP, Calfon M, Urano F, Novoa I, Ron D: Transcriptional and translational control in the Mammalian unfolded protein response. Annu Rev Cell Dev Biol. 2002, 18: 575-799. 10.1146/annurev.cellbio.18.011402.160624.CrossRefPubMed
25.
go back to reference Qin L, Wang Z, Tao L, Wang Y: ER stress negatively regulates AKT/TSC/mTOR pathway to enhance autophagy. Autophagy. 2010, 6: 239-247. 10.4161/auto.6.2.11062.CrossRefPubMed Qin L, Wang Z, Tao L, Wang Y: ER stress negatively regulates AKT/TSC/mTOR pathway to enhance autophagy. Autophagy. 2010, 6: 239-247. 10.4161/auto.6.2.11062.CrossRefPubMed
Metadata
Title
Inhibition of autophagy enhances the cytotoxic effect of PA-MSHA in breast cancer
Authors
Wen-Huan Xu
Zhe-Bin Liu
Yi-Feng Hou
Qi Hong
Da-Li Hu
Zhi-Ming Shao
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-273

Other articles of this Issue 1/2014

BMC Cancer 1/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine