Abstract
Previous clinical studies showed that menstruating females were better protected in melanoma than post-menopausal women and men of any age. In addition, epidemiological studies showed an increased male mortality in melanoma. But these studies did not correlate with steroid status in females. Our in-vitro study showed female sex hormone progesterone significantly inhibited human melanoma cell growth. Further in-vitro study showed that progesterone action was mediated by a specific suppression of pro-inflammatory cytokine IL-8. Our research also showed that addition of IL-8 (1 ng/ml) to melanoma cells stimulated cell growth (117%) and suppression of IL-8 by curcumin (100 μM) pre-treatment suppressed human melanoma cell growth (26%) in-vitro. This observation prompted us to check the effect of male sex hormones androstenedione (AD) and testosterone (T) on melanoma cell growth. AD and T also suppressed cell growth and IL-8 secretion, but not as significantly as that of progesterone. However, addition of progesterone (10 μM) along with androgens showed an additive effect on the inhibition of melanoma cell growth and suppression of IL-8 secretion. As steroids (P, AD, T) targeted IL-8 for their action, it was decided to check whether vitamin-D3 also targeted IL-8 secretion and cell growth. Active form of vit-D3 (25 μM) also suppressed IL-8 secretion and cell growth. But, addition of progesterone (50 μM) along with D3 significantly suppressed cell growth and IL-8 secretion. This brought IL-8 into focus as a key molecule regulating melanoma cell growth. In order to check whether IL-8 was the molecule involved in regulating melanoma cell growth, IL-8 rescue experiment after curcumin (25 μM) pre-treatment was carried out. IL-8 (100 ng/ml) was able to rescue cell growth completely after pre-treatment with curcumin, suggesting IL-8 was the molecule involved in regulating melanoma cell growth. Literature also suggested important role for IL-8 in regulating melanoma cell growth. Conditional expression of IL-8 in nude mouse by Dr. Singh et al., indicated in-vivo role of IL-8 in melanoma growth and metastasis. Conclusion: Both, in-vitro and in-vivo studies suggested an important role for IL-8 in regulating melanoma growth and metastasis. So, IL-8 could be targeted to arrest melanoma growth and metastasis in-vivo. Hence, IL-8 could be a potential target for melanoma treatment.
Induction of matrix metalloproteinase gene transcription by nitric oxide and mechanisms of MMP-1 gene induction in human melanoma cell lines
