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
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 conta...
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Published in | Neuro-oncology (Charlottesville, Va.) Vol. 20; no. suppl_3; p. iii297 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
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Oxford University Press
19.09.2018
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Abstract | 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. |
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AbstractList | 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. |
Author | Ozpinar, A Baskan, O Bilir, A Elmaci, I Altinoz, M A |
AuthorAffiliation | 2 Histology and Embryology, Aydin University, Istanbul, Turkey 4 Dept of Radiology, Memorial Hospital, Istanbul, Turkey 1 Dept of Neurosurgery, Memorial Hospital, Istanbul, Turkey 3 Dept of Biochemistry, Acibadem University, Istanbul, Turkey |
AuthorAffiliation_xml | – name: 1 Dept of Neurosurgery, Memorial Hospital, Istanbul, Turkey – name: 2 Histology and Embryology, Aydin University, Istanbul, Turkey – name: 4 Dept of Radiology, Memorial Hospital, Istanbul, Turkey – name: 3 Dept of Biochemistry, Acibadem University, Istanbul, Turkey |
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Copyright | The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2018 |
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Risk of high-grade gliomas is lower in young females and its incidence enhances after menopause suggesting a likely protective role of... |
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Title | 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 |
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