Can Interleukin‐8 Alone be Responsible for Regulating Melanoma Growth & Metastasis? In‐vitro studies based on treatments of human melanoma cell lines (BLM and 1205Lu) with sex steroids, IL‐8, curcumin and active vitamin‐D3

Abstract

Previous clinical studies indicated that menstruating females were better protected in melanoma than post‐menopausal women and men of any age. But, the mechanism responsible for protection in menstruating females was not investigated. In addition, epidemiological data showed an increased male mortality in melanoma. Our in‐vitro study showed female sex hormone progesterone significantly inhibited human melanoma cell growth. Elisarray showed that progesterone action was mediated by a specific suppression of pro‐inflammatory cytokine IL‐8. So, the effect of male sex hormones androstenedione (AD) and testosterone (T) on melanoma cell growth was checked. AD and T also suppressed cell growth and IL‐8 secretion. But, addition of progesterone (10μM) along with androgens showed an additive effect on the inhibition of melanoma cell growth and IL‐8 suppression. This observation gave the idea of protective function of progesterone in melanoma, which was experimentally observed by a significant decrease in in‐vitro migration and adhesion functions. As steroids (P, AD, T) targeted IL‐8 for their actions, effect of vit‐D3 on melanoma cells was checked. Active form of vitamin‐D3 (25 μM) also targeted IL‐8 and decreased cell growth, suggesting IL‐8 could be regulating melanoma cell growth. In order to check whether IL‐8 regulated melanoma cell growth, IL‐8 was directly added to melanoma cells and endogenous IL‐8 was suppressed by 2 hrs pre‐treatment with curcumin. Addition of IL‐8 (1 ng/ml) to 1205Lu melanoma cells stimulated cell growth to 117%, whereas suppression of IL‐8 by curcumin (100 μM) pre‐treatment decreased cell growth to 24%. Similar results were obtained with BLM cells. This brought IL‐8 into focus as an important molecule regulating melanoma cell growth. Further in‐vitro experiments to restore curcumin (25 μM) pre‐treated melanoma cell growth (71.5%) by the addition of IL‐8 (100 ng/ml) resulted in a near complete restoration of cell growth (95.3%) in 1205Lu melanoma cells, suggesting IL‐8 could be the molecule regulating melanoma cell growth. Similar results were observed with BLM cells. In addition, in‐vivo conditional expression of IL‐8 in nude mouse by Dr. Singh et al., indicated involvement of IL‐8 in melanoma growth and metastasis.ConclusionBoth in‐vitro and in‐vivo studies indicated that IL‐8 alone could be responsible for regulating melanoma growth and metastasis. Hence, IL‐8 could be targeted to arrest melanoma growth and metastasis in‐vivo.