Biochemical Basis of Steroid Hormones Inhibition of Human Melanoma Cell Growth In‐Vitro & Its Implication on Melanoma Treatment

Abstract

Skin, as an endocrine organ produced various hypothalamic, pituitary, adrenal and sex steroids. Steroids were not only important for healthy skin, but were also shown to influence locally and systemically. This raised the question whether melanoma was a hormone‐dependent cancer. But to the contrary, clinical study showed that menstruating females were better protected in melanoma than post‐menopausal women and men of any age. Literature showed that progesterone (P) level varied in menstruating females between 1000 to 1500 ng/dL. Whereas in post‐menopausal women, progesterone ranged between 20 to 100 ng/dL and in males between 27 – 90 ng/dL. In addition, our in‐vitro research showed that progesterone significantly inhibited human melanoma (BLM) cell growth. So, it was hypothesized that progesterone could be protecting menstruating females in melanoma. Further research showed that androgens (androstenedione, AD and testosterone, T) also inhibited human melanoma cell growth in‐vitro, but only at high concentrations (100 μM and 200 μM). Co‐incubation of AD and T separately with P showed an additive effect on BLM cell growth inhibition, suggesting the protective function of P. In order to find out the biochemical basis of steroid hormones action, Elisarray was carried out on the supernatants. There was a specific suppression of IL‐8 cytokine in the supernatants of AD, P and AD+P co‐incubated cells compared to untreated control BLM cells. Same experiments were repeated on another human melanoma (1205Lu) cell line, which also showed a specific suppression of IL‐8 cytokine. The decrease in IL‐8 was quantitated by Elisa, which correlated with the decrease in melanoma cell growth. To further confirm, experiments with T, P and T+P were carried out on BLM and 1205Lu cell lines, which also showed a specific suppression of IL‐8 by Elisarray. In addition, Kanda and Watanabe already showed that dihydrotestosterone and estrogen also suppressed IL‐8 in melanoma cells.ConclusionSuppression of IL‐8 resulting in the suppression of melanoma cell growth, implied the important role of IL‐8 in regulating melanoma growth. But suppression of IL‐8 in turn by various steroids, indicated the local regulation by the steroids. Local regulation in turn indicated the role of steroids in regulating melanoma growth. Hence, balancing or restoring local steroid hormones along with targeted or immuno therapy could be an ideal treatment for melanoma.Support or Funding Information1) Start‐up grant to PR2) Biomedical Sciences research grant3) Warner/Fermaturo research grantThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.