Hormones dictate the state and functionality of everyone’s body. One type of hormone is progesterone. Dr. Meharvarn Singh worked with progesterone regarding menopausal women. When women experience menopause, estrogen suffers an extreme loss. He found that following the loss of estrogen, cognitive discussion becomes harder. This laid the groundwork for understanding what is typically considered “sex hormones,” which can be involved outside of sex functions. Additionally, Dr. Singh explored whether progesterone can partially restore and/or protect estrogen during menopause. Combining it with the androgen testosterone, he found that certain mixtures of androgen receptors, the cancer drug Temozolomide, and other components protected estrogen while others constituted cell death.
Dr. Mariangela Tamburello and colleagues further researched progesterone’s protective capabilities through Adrenocortical Carcinoma (ACC). Previous research indicated that an increase in progesterone inhibited the proliferation of breast cancer cells. They completed another study and proved the previous finding by using abiraterone acetate therapeutically. Using their previous success as a basis, they drove to expand and understand how progesterone affects ACC metastatic cell lines of MUC-1 and TVBF-7. Furthermore, they sought to understand if progesterone influenced ACC cell growth alongside invasive and metastasis formation in vitro and in vivo. Finally, they desired to map out the molecular mechanism regarding the cytotoxic effect or cell damage.
To determine the cytotoxic effect, they injected either 6.25 or 12.5 µM of progesterone into mice embryos with NCI-2H95R, MUC-1, and TVBF-7. They found that progesterone was able to reduce tumor mass when given the 6.25µM dose in all three. Strikingly, the injection of 12.5µM resulted in high mortality rates with MUC-1. Despite that, MUC-1’s alarmingly fast spread rate slowed significantly with the administration of progesterone. NCI-2H95R, on the other hand, showed a slow spread rate and a lack of modification due to progesterone.
Dr. Tamburello and colleagues additionally researched the relationship between Metalloproteases or MMPs. This is the factor that allows for the spread of cancer cells. At first, they were unable to observe anything significant, so they did a western blot analysis. They found that progesterone significantly reduced MMP2 levels when compared to untreated cells. Ultimately, no significant differences could be observed in NCI-2H95R cells after treatment. This is concerning NCI-2H95R’s inability to spread the cancer cells.
Finally, they studied the effects of progesterone during treatment withdrawal. They treated the cells for 4 days and then let them sit in a drug-free medium for 10 days. They found that NCI-2H95R cells maintained the effects of progesterone for 2 days. After that, the cultures began to resemble that of an untreated cell. MUC-1 cells suffered from damage, causing viability to decrease during the duration. Furthermore, TVBF-7 cells did not suffer a decline. The cells slowly recovered but were still victims to a loss of viability. This concludes that progesterone caused an influx of damaged cells as the drug continued to remain absent.
References
Singh M, Krishnamoorthy VR, Kim S, Khurana S and LaPorte HM (2024) Brain-derived neuerotrophic factor and related mechanisms that mediate and influence progesterone-induced neuroprotection. Front. Endocrinol. 15:1286066. doi: 10.3389/fendo.2024.1286066
Tamburello, M.; Abate, A.; Rossini, E.; Basnet, R.M.; Zizioli, D.; Cosentini, D.; Hantel, C.; Laganà, M.; Tiberio, G.A.M.; Grisanti, S.; et al. Preclinical Evidence of Progesterone as a New Pharmacological Strategy in Human Adrenocortical Carcinoma Cell Lines. Int. J. Mol. Sci. 2023, 24, 6829. https://doi.org/10.3390/ijms24076829
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