From epidemiology and neurodevelopment to antineoplasticity. Medroxyprogesterone reduces human glial tumor growth in vitro and C6 glioma in rat brain in vivo

Altinöz, Meriç A.; Nalbantoglu, Joséphine; Özpınar, Aysel; Özcan, Muhammed Emin; Maestro, Rolando F. Del; Elmacı, İlhan

doi:10.1016/j.clineuro.2018.07.012

Cited by 11 publications

(14 citation statements)

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“…P4 hormone and its analogs are highly safe at very large doses and act anti-neoplastic via different mechanisms than cytotoxic chemotherapeutics. 1,2 Therefore, hormone-sensitizing agents can be developed to enhance the antineoplastic of P4 even further. Fortunately, there exist many preclinical and even clinical data that showed agents capable to enhance the antineoplastic of P4 analogs including MPA.…”

Section: Discussionmentioning

confidence: 99%

“…Glioblastoma multiforme (GBM) has an extremely grave prognosis with approximately 15 months of overall survival despite the golden standard of care. 1,2 Therefore, the proposal for innovative treatment regimes is of crucial importance. Despite some controversies, many available studies demonstrate that female gender, parity, and hormone replacement treatment reduce the risk of GBMs, while the reverse is true for meningiomas.…”

Section: Introductionmentioning

confidence: 99%

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Progesterone at high doses reduces the growth of U87 and A172 glioblastoma cells: Proteomic changes regarding metabolism and immunity

et al. 2020

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While pregnancy may accelerate glioblastoma multiforme (GBM) growth, parity and progesterone (P4) containing treatments (ie, hormone replacement therapy) reduce the risk of GBM development. In parallel, low and high doses of P4 exert stimulating and inhibitory actions on GBM growth, respectively. The mechanisms behind the high‐dose P4‐suppression of GBM growth is unknown. In the present study, we assessed the changes in growth and proteomic profiles when high‐dose P4 (100 and 300 µM) was administered in human U87 and A172 GBM cell lines. The xCELLigence system was used to examine cell growth when different concentrations of P4 (20, 50, 100, and 300 µM) was administered. The protein profiles were determined by two‐dimensional gel electrophoresis in both cell lines when 100 and 300 µM P4 were administered. Finally, the pathways enriched by the differentially expressed proteins were assessed using bioinformatic tools. Increasing doses of P4 blocked the growth of both GBM cells. We identified 26 and 51 differentially expressed proteins (fc > 2) in A172 and U87 cell lines treated with P4, respectively. Only the pro‐tumorigenic mitochondrial ornithine aminotransferase and anti‐apoptotic mitochondrial 60 kDa heat shock protein were downregulated in A172 cell line and U87 cell line when treated with P4, respectively. Detoxification of reactive oxygen species, cellular response to stress, glucose metabolism, and immunity‐related proteins were altered in P4‐treated GBM cell lines. The paradox on the effect of low and high doses of P4 on GBM growth is gaining attention. The mechanism related to the high dose of P4 on GBM growth can be explained by the alterations in detoxification mechanisms, stress, and immune response and glucose metabolism. P4 suppresses GBM growth and as it is nontoxic in comparison to classical chemotherapeutics, it can be used as a new strategy in GBM treatment in the future.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Progesterone at high doses reduces the growth of U87 and A172 glioblastoma cells: Proteomic changes regarding metabolism and immunity

et al. 2020

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“…A recent proteomic analysis, conducted by Altinoz and cols suggests that suppressive actions of high doses of P4 on glioblastoma are induced by changes in detoxification mechanisms, stress, immune response, and glucose metabolism [13]. High doses of medroxyprogesterone acetate, a synthetic variant of P4, have also shown antiproliferative effects on glioblastoma-derived cell lines such as C6 and U87 [72].…”

Section: Gonadal Steroid Hormones In Prevalence and Progression In Glioblastoma: P4mentioning

confidence: 99%

Impact of sex in the prevalence and progression of glioblastomas: the role of gonadal steroid hormones

Bello-Álvarez

2021

Biol Sex Differ

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Background As in other types of cancers, sex is an essential factor in the origin and progression of glioblastomas. Research in the field of endocrinology and cancer suggests that gonadal steroid hormones play an important role in the progression and prevalence of glioblastomas. In the present review, we aim to discuss the actions and mechanism triggered by gonadal steroid hormones in glioblastomas. Main body Glioblastoma is the most common malignant primary brain tumor. According to the epidemiological data, glioblastomas are more frequent in men than in women in a 1.6/1 proportion both in children and adults. This evidence, and the knowledge about sex influence over the prevalence of countless diseases, suggest that male gonadal steroid hormones, such as testosterone, promote glioblastomas growth. In contrast, a protective role of female gonadal steroid hormones (estradiol and progesterone) against glioblastomas has been questioned. Several pieces of evidence demonstrate a variety of effects induced by female and male gonadal steroid hormones in glioblastomas. Several studies indicate that pregnancy, a physiological state with the highest progesterone and estradiol levels, accelerates the progression of low-grade astrocytomas to glioblastomas and increases the symptoms associated with these tumors. In vitro studies have demonstrated that progesterone has a dual role in glioblastoma cells: physiological concentrations promote cell proliferation, migration, and invasion while very high doses (out physiological range) reduce cell proliferation and increases cell death. Conclusion Gonadal steroid hormones can stimulate the progression of glioblastomas through the increase in proliferation, migration, and invasion. However, the effects mentioned above depend on the concentrations of these hormones and the receptor involved in hormone actions. Estradiol and progesterone can exert promoter or protective effects while the role of testosterone has been always associated to glioblastomas progression.

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“…Uzun yıllardır tedavi seçenekleri ile ilgili çok sayıda klinik ve deneysel çalışmalar yapılmış olmasına rağmen, standart tedavisinde ciddi bir değişiklik olmamıştır (5)(6)(7)(8). Bu hâliyle GBM'in birincil tedavisi hâlen, tümörün mümkün olan geniş ve güvenli şekilde rezeksiyonudur (9,10).…”

Section: Introductionunclassified

Epidemiology, Treatment Options and Survival Analysis of Glioblastoma Multiforme: A Retrospective Single Center Study

Keskin

Elmas

Aydin

et al. 2021

Batı Karadeniz Tıp Dergisi

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ÖZAmaç: Glioblastoma multiforme (GBM), primer beyin tümörlerinin en sık görülenidir. Tedavisi ile ilgili çok sayıda klinik ve deneysel çalışma yapılmasına rağmen; GBM'in tedavi seçenekleri çok fazla değişmemiştir. Çalışmamız, GBM'li hastaların epidemiyolojisi, tedavi seçenekleri ve sağkalım süreleri arasındaki ilişkiyi incelemek amacıyla planlandı.Gereç ve Yöntemler: Bu çalışmada, 2017-2019 yılları arasında Zonguldak Bülent Ecevit Üniversitesi Tıp Fakültesi Beyin ve Sinir Cerrahisi Anabilim Dalı'nda GBM tanısı alan 72 hasta retrospektif olarak değerlendirilmiştir. Bu hastaların tedavi modaliteleri, epidemiyolojileri ve sağkalım süreleri incelenmiştir. Bulgular: Hastaların 28'i kadın, 44'ü erkek olup, %55,6'sı 60 yaş üstüdür. Cinsiyet ile sağkalım süresi arasındaki fark istatistiksel olarak anlamlı değildir (p=0,303>0,05). Yaş arttıkça sağkalım süresinde %28,9 oranında azalış olduğu görülmüştür. GBM lokalizasyon olarak en sık temporopariyatel yerleşimli olduğu gözlenirken, tümör lokalizasyonu ile sağkalım süresi arasında anlamlı fark görülmedi.Sonuç: Çalışmamızın sonucunda GBM'li hastalarda, yaşın ve kombine tedavi seçeneğinin önemli bir prognostik faktörler olduğu görülmüştür.

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From epidemiology and neurodevelopment to antineoplasticity. Medroxyprogesterone reduces human glial tumor growth in vitro and C6 glioma in rat brain in vivo

Cited by 11 publications

References 65 publications

Progesterone at high doses reduces the growth of U87 and A172 glioblastoma cells: Proteomic changes regarding metabolism and immunity

Progesterone at high doses reduces the growth of U87 and A172 glioblastoma cells: Proteomic changes regarding metabolism and immunity

Impact of sex in the prevalence and progression of glioblastomas: the role of gonadal steroid hormones

Epidemiology, Treatment Options and Survival Analysis of Glioblastoma Multiforme: A Retrospective Single Center Study

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