Autophagy and Nuclear Changes in FM3A Breast Tumor Cells after Epirubicin, Medroxyprogesterone and Tamoxifen Treatment in vitroBilir A.a · Altinoz M.A.a · Erkan M.c · Ozmen V.b · Aydiner A.d
Departments of aHistology and Embryology and bSurgery, Istanbul Medical Faculty, cDepartment of Biology, Faculty of Science, dOncology Institute, Istanbul University, Istanbul, Turkey
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Objective: Autophagy is a form of physiological programmed cell death which is observable after hormonal withdrawal. In this study, the FM3A murine breast tumor cell line was treated with epirubicin alone and with medroxyprogesterone acetate (MPA) or tamoxifen, to determine if structural and kinetic signs of autophagy may also occur in an enhanced manner during epirubicin sensitization via hormonal agents. Methods: One-week soft agar colony growth, 96-hour values of plating and pulse thymidine labeling and electron microscopical examinations were performed following treatment with MPA and tamoxifen alone or with epirubicin. Results: Tamoxifen induced signs of autophagy, which was enhanced when it was combined with MPA. Epirubicin also induced autophagy of secretory granules, which coalesced to form an intracytoplasmic lumen. Combining MPA with epirubicin enhanced the formation of apoptotic blebs and chromatin fragmentation. When epirubicin was combined with tamoxifen, peculiar nuclear structures were formed. Conclusions: Hormonal agents may modulate anthracycline activity towards specific patterns in eliciting cell death, via autophagy and/or as yet unknown nucleolus-specific interactions.
© 2002 S. Karger AG, Basel
- Xue L, Fletcher GC, Tolkovsky AM: Autophagy is activated by apoptotic signalling in sympathetic neurons: An alternative mechanism of death execution. Mol Cell Neurosci 1999;14:180–198.
- Berciano MT, Fernandez R, Pena E, Calle E, Villagra NT, Lafarga M: Necrosis of Schwann cells during tellurium-induced primary demyelination: DNA fragmentation, reorganization of splicing machinery, and formation of intranuclear rods of actin. J Neuropathol Exp Neurol 1999;58:1234–1243.
- Chi S, Kitanaka C, Noguchi K, Mochizuki T, Nagashima Y, Shirouzu M, Fujita H, Yoshida M, Chen W, Asai A, Himeno M, Yokoyama S, Kuchino Y: Oncogenic ras triggers cell suicide through the activation of a caspase-independent cell death program in human cancer cells. Oncogene 1999;18:2281–2290.
Bruchovsky N, Van Doorn E: Steroid receptor proteins and regulation of growth in mammary tumors. Recent results. Cancer Res 1976;57:121–142.
- Bursch W, Hochegger K, Torok L, Marian B, Ellinger A, Herrmann RS: Autophagic and apoptotic types of programmed cell death exhibit different fates of cytoskeletal filaments. J Cell Sci 2000;113:1189–1198.
- Wilson MJ, Whitaker JN, Sinha AA: Immunocytochemical localization of cathepsin D in rat ventral prostate: Evidence for castration-induced expression of cathepsin D in basal cells. Anat Rec 1991;229:321–333.
- Lupulescu A: Chemoprotective effect of progesterone on carcinoma formation in mice and rats. J Natl Cancer Inst 1985;74:499–507.
- Butler R, Mitchell SH, Tindall DJ, Young CY: Nonapoptotic cell death associated with S-phase arrest of prostate cancer cells via the peroxisome proliferator-activated receptor γ ligand 15-deoxy-delta12,14-prostaglandin J2. Cell Growth Differ 2000;11:49–61.
- Serafino A, Sinibaldi-Vallebona P, Pierimarchi P, Bernard P, Gaudiano G, Massa C, Rasi G, Ranagnan G: Induction of apoptosis in neoplastic cells by anthracycline antitumor drugs: Nuclear and cytoplasmic triggering? Anticancer Res 1999;19:1909–1918.
- Fornari FA Jr, Jarvis WD, Grant S, Orr MS, Randolph JK, White FK, Mumaw VR, Lovings ET, Freeman RH, Gewirtz DA: Induction of differentiation and growth arrest associated with nascent (nonoligosomal) DNA fragmentation and reduced c-myc expression in MCF-7 human breast tumor cells after continuous exposure to a sublethal concentration of doxorubucin. Cell Growth Differ 1994;5:723–733.
- Moulton BC, Koenig BB: Progestin increases cathepsin D synthesis in uterine luminal epithelial cells. Am J Physiol 1983;244:E442–E446.
- Kester HA, van der Leede BM, van der Saag PT, van der Burg B: Novel progesterone target genes identified by an improved differential display technique suggest that progestin-induced growth inhibition of breast cancer cells coincides with enhancement of differentiation. J Biol Chem 1997;272:16637–16643.
- Gard DL: Ectopic spindle assembly during maturation of Xenopus oocytes: Evidence for functional polarization of the oocyte nucleus. Dev Biol 1993;159:298–310.
- Long BH, Willis CE, Prestayko AW, Crooke ST: Effect of anthracycline analogues on the appearance of newly synthesized total RNA and messenger RNA in the cytoplasm of erythroleukemia cells. Mol Pharmacol 1982;22:152–157.
- Dantchev D, Balercia G, Bourut C, Anjo A, Maral R, Mathe G: Comparative microscopic study of cardiotoxicity and skin toxicity of anthracycline analogs. Biomed Pharmacother 1984;38:322–328.
- Solaini G, Ronca G, Bertelli A: Inhibitory effects of several anthracyclines on mitochondrial respiration and coenzyme Q10 protection. Drugs Exp Clin Res 1985;11:533–537.
- Merski JA, Daskal I, Busch I: Effects of adriamycin on ultrastructure of nucleoli in the heart and liver cells of the rat. Cancer Res 1976;36:1580–1584.
- Lambertenghi-Deliliers G, Zanon PL, Pozzoli EF, Bellini O: Myocardial injury induced by a single dose of adriamycin: An electron microscopic study. Tumori 1976;62:517–528.
- Merski J, Daskal Y, Busch H: Comparison of adriamycin-induced nucleolar segregation in skeletal muscle, cardiac muscle and liver cells. Cancer Treat Rep 1978;62:771–778.
- Lampidis TJ, Henderson IC, Israel M, Canellos GP: Structural and functional effects of adriamycin on cardiac cells in vitro. Cancer Res 1980;40:3901–3909.
- Daskal Y, Woodard C, Crooke ST, Busch H: Comparative ultrastructural studies of nucleoli of tumor cells treated with adriamycin and the newer anthracyclines, carminomycin and marcellomycin. Cancer Res 1978;38:467–473.
- Cavanagh JB, Tomiwa K, Munro PMG: Nuclear and nucleolar damage in adriamycin-induced toxicity to rat sensory ganglion cells. Neuropathol Appl Neurobiol 1987;13:23–38.
- Vaidyanathan S, Borojuerdi M: Effect of tamoxifen pretreatment on the pharmacokinetics, metabolism and cardiotoxicity of doxorubicin in female rats. Cancer Chemother Pharmacol 2000;46:185–192.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.