**2.2 Clinical studies**

Overall survival outcome for young women (45 years of age and under) was far superior to older women (55 years of age and older) and men of any age group [20]. A 22% survival advantage and 17% 5 year disease-free interval advantage were observed in females [21]. In addition, women were found to survive longer than men after the development of stage III disease [22]. Clinical studies also suggested the involvement of hormones in the regulation of melanoma growth. So, clinical studies underlined the involvement of female sex steroid hormones in protecting menstruating females in melanoma. But, these clinical studies did not identify the exact female hormone involved in the protection. In addition, there was no statistically significant difference observed in the survival rates between controls and women diagnosed with melanoma stage I or stage II during pregnancy [23–25]. Data also showed no correlation between melanoma and oral contraceptives

**45**

*Hormonal Regulation of Cutaneous Melanoma: A Brief Review of In Vivo and In Vitro Studies…*

[26, 27]. Available data suggested no connection between exogenous hormones and

The following in vitro studies showed inhibitory effect of steroid hormones on a variety of melanoma cell lines, suggesting melanoma could be a hormone-sensitive cancer:

b.Kanda and Watanbe showed that 17-β-estradiol, progesterone, and dihydrotestosterone inhibited melanoma cell growth in a receptor-dependent manner by

c.Amelanotic strain cells grew faster in vivo in female hamsters [32], whereas

d.Glucocorticoids also showed their effect on melanoma cell growth in a

e.Another in vitro study showed that melatonin at physiological concentrations (1 nM to 10 pM) inhibited metastatic mouse melanoma (B16BL6) cell

Our lab in vitro studies showed involvement of progesterone in the regulation of

**4.1 Dose-response studies of progesterone with mouse (B16F10) and human** 

**4.2 Mechanism of inhibition of human melanoma (BLM) cell growth**

Initially four sex steroids, viz., dehydroepiandrosterone (DHEA), androstenedione (AD), testosterone (T), and progesterone (P4), were checked for their effect on mouse melanoma (B16F10) cell growth [35]. Though all four steroids showed a dose-dependent effect, progesterone showed a significant effect on the inhibition of mouse melanoma cell growth (**Figure 1**). As the initial study was carried out at high concentrations (100, 150, and 200 μM), dose-response study was carried out to rule out toxic effect of high concentrations of steroids on melanoma cell growth inhibition. Mouse (B16F10) and human melanoma (BLM) cells showed a dose-dependent cell growth inhibition [35, 36], suggesting the inhibition was not due to toxic effect

After having ruled out necrosis and apoptosis as the cause of cell growth inhibition, it was found out that autophagy was the mechanism of cell growth inhibition (**Figure 2**), using a known inducer of autophagy (spermidine) in a control experiment [36].

a.2-Methoxyestradiol (2-ME), an estrogenic metabolite, inhibited all tested melanoma cell line growth, without affecting the growth of non-tumorigenic

*DOI: http://dx.doi.org/10.5772/intechopen.86593*

the risk for malignant melanoma [28, 29].

suppressing IL-8 transcription [31].

receptor-dependent manner [33].

**4. In vitro studies from our lab**

**melanoma (BLM) cell line**

mouse and human melanoma cell growth.

at high concentration of steroids (**Figure 1**).

testosterone inhibited the cell growth in vitro.

**3. Brief review of in vitro studies**

cells [30].

growth [34].

*Hormonal Regulation of Cutaneous Melanoma: A Brief Review of In Vivo and In Vitro Studies… DOI: http://dx.doi.org/10.5772/intechopen.86593*

[26, 27]. Available data suggested no connection between exogenous hormones and the risk for malignant melanoma [28, 29].
