P04.75 Tibolone, an estrogenic progestin of hormone replacement therapy reduces colony formation and 3-dimensional spheroid S-phase in C6 rat glioma in vitro

• Published in: Neuro-oncology (Charlottesville, Va.) Vol. 20; no. suppl_3; p. iii297
• Main Authors: Altinoz, M A, Bilir, A, Ozpinar, A, Baskan, O, Elmaci, I
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 19.09.2018
• Subjects: Poster Presentations
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/noy139.309

Abstract Background Risk of high-grade gliomas is lower in young females and its incidence enhances after menopause suggesting a likely protective role of female hormones. Hormone replacement therapy (HRT) is being employed to treat osteoporosis and some epidemiological studies showed that HRT containing progesterone analogs decrease the risk of glial tumors. Tibolone is a unique progesterone analog used in HRT with tissue-specific estrogenic effects. According to some studies, tibolone may enhance the risk of mammary and female reproductive cancers; but peculiarly, there exist several basic scientific data that it acts antitumoral at higher concentrations than which can be achieved in HRT. This feature resembles to another progesterone analog, medroxyprogesterone acetate (MPA). MPA enhances risk of breast cancer in HRT protocols; nonetheless, at high dosages, it can cause regression of far advanced breast, endometrium and renal cancers. Moreover, molecular studies have shown that MPA and tibolone induce very similar gene expression patterns. Since tibolone’s pro-estrogenic effects occur particularly in bone and brain, we have hypothesized that high dose tibolone with both progestagenic and estrogenic actions may block glioma growth alone and/or in synergy with MPA or temozolomide. Material and Methods Soft agar colony assay, 3H-thymidine test to determine the S-phase (DNA synthesis phase) and transmission electron microscopy were performed to determine the effects of tibolone on C6 rat glioma. Results Tibolone dose-dependently blocked soft agar colony growth of C6 glioma. Tibolone potentiated MPA-induced growth inhibition in soft agar colonies. Tibolone potentiated temozolomide’s effect in reducing colony growth. Tibolone inhibited DNA synthesis in C6 rat glioma spheroids (as assessed by BrdU-labeling index) to similar levels which can be achieved with temozolomide. Transmission electron microscopical analyses revealed that mutual interactions between tibolone, MPA and temozolomide involve mitochondrial condensation, mitophagy and autophagy. Conclusion Tibolone merits to be studied in further models of glioblastoma in vitro and in vivo.