Role of endoplasmic reticulum stress induction by the plant toxin, persin, in overcoming resistance to the apoptotic effects of tamoxifen in human breast cancer cells
| Autor: | Robert Ian Nicholson, Elizabeth A. Musgrove, Ebru Boslem, Andrew Burgess, Rachael A. McCloy, Robert L. Sutherland, Julia Margaret Wendy Gee, Caroline G. Roberts, A. J. Butt, Trevor J. Biden, E. J. Shelley |
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| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
medicine.medical_specialty RM Breast Neoplasms Persin Biology RC0254 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine breast cancer Internal medicine Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols medicine Neoplasm Humans skin and connective tissue diseases persin 030304 developmental biology 0303 health sciences tamoxifen Plant Extracts Endoplasmic reticulum apoptosis Drug Synergism medicine.disease Endoplasmic Reticulum Stress 3. Good health Endocrinology Oncology chemistry Apoptosis Cell culture Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer cell Cancer research MCF-7 Cells Female Signal transduction Fatty Alcohols Translational Therapeutics Tamoxifen medicine.drug Signal Transduction |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | Background:\ud Persin is a plant toxin that displays synergistic cytotoxicity with tamoxifen in human breast cancer cell lines. Here, we examined the ability of persin to circumvent tamoxifen resistance and delineated the intracellular signalling pathways involved.\ud Methods:\ud The induction of apoptosis in tamoxifen-resistant and -sensitive breast cancer cells was measured by flow cytometry following treatment with persin±tamoxifen. Markers of endoplasmic reticulum stress (ERS) were analysed following treatment, and their causal role in mediating persin-induced apoptosis was determined using chemical inhibitors and RNA interference.\ud Results:\ud Cells that were resistant to an apoptotic concentration of tamoxifen maintained an apoptotic response to persin. Persin-induced apoptosis was associated with an increase in markers of ERS, that is, CHOP expression and XBP-1 splicing and was decreased by CHOP siRNA. The CASP-4 inhibitor Z-YVAD-FMK markedly inhibited persin-induced apoptosis in both tamoxifen-sensitive and -resistant cells.\ud Conclusion:\ud The cytotoxic effects of persin are CASP-4 dependent and mediated by CHOP-dependent and -independent ERS signalling cascades. Increased ERS signalling contributes to persin-induced reversal of tamoxifen resistance. |
| Databáze: | OpenAIRE |
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