Sulforaphane in Skin Cancer Prevention: mechanisms of action and potential in vivo limitations
Introduction: Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables that is associated with the prevention of multiple cancers1. Skin cancer incidence is on the rise globally and can be resistant to treatments2,3. Studies investigating the role of SFN in skin cancer prevention have shown that SFN may help to prevent the development of skin cancer through multiple mechanisms including: Nrf2-Keap1 signaling, apoptosis induction, cell cycle arrest, and others4-7. Despite these results, questions of SFN’s effectiveness in vivo due to the influence of biological elements is an ongoing discussion. Methods: JB6 P+ mouse epidermal cells were used to study the effect of SFN pretreatment on cell colony formation upon incubation with TPA, a tumor promoting agent5. Additional studies have analyzed the effects of SFN on cell cycle arrest and induction of apoptosis utilizing human melanoma cell lines A375 and 501-MEL against control HEMa human epidermal cells6. A follow-up study utilizing A375 human melanoma cell lines looked at the effect of the biological element Nerve Growth Factor (NGF) in SFN treatment8. Results: JB6 P+ cells incubated with TPA showed a reduction in colony formation by 55% and 66% when pretreated with 2.5 and 5.0µmol of SFN respectively (p<0.05, p<0.01)5. Knockdown of Nrf2 in JPB 6+ cells showed a reduction in the inhibition of colony formation despite SFN pretreatment. These findings suggest that Nrf2 is involved in SFN’s inhibition of colony formation. In addition to cancer preventive effects via Nrf2 signaling, treatment of A375 and 501-MEL human melanoma cells with SFN for 24 or 48 hours led to an increase of apoptotic cells and to an accumulation of cells in the G2/M cell cycle phase as compared to HEMa control cells6. In a follow-up study, SFN’s protective effects in A375 cell lines were reduced in the presence of NGF8. When SFN was combined with NGF the percentage of cells in G2/M arrest and apoptotic cells declined. This finding suggests that biological elements like NGF may limit SFN’s mechanisms of action. Conclusions: Studies of sulforaphane in cancer prevention have promising results, suggesting that SFN may prevent carcinogenesis through multiple mechanisms. As skin care incidence continues to rise finding alternative methods of prevention is essential. Despite promising results, SFN’s effectiveness in vivo is not well understood and a preliminary study in A375 cell lines suggests biological elements may limit its use. Additional studies are needed to better understand SFN’s in vivo effectiveness.
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