Mintie Charlotte A, Musarra Anna K, Singh Chandra K, Ndiaye Mary A, Sullivan Ruth, Eickhoff Jens C, Ahmad Nihal
Department of Dermatology, University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USA.
Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53706, USA.
Cancers (Basel). 2020 Jul 1;12(7):1751. doi: 10.3390/cancers12071751.
Non-melanoma skin cancers (NMSCs) are the most diagnosed cancers in the US and occur more frequently in males. We previously demonstrated chemoprotective effects of dietary grape powder (GP) against UVB-mediated skin tumorigenesis in female SKH-1 mice. To expand on this, here, we determined the effects of GP in a short-term UVB exposure protocol (0 or 5% GP, followed by UVB every other day for 2 weeks) in male and female SKH-1 mice, as well as explored any sex-related differences in UVB carcinogenesis via male SKH-1 mice (0, 3, or 5% GP; UVB twice weekly for 28 weeks). In the short-term study, we found that GP protects against early-stage epithelial hyperplasia and mast cell infiltration in both sexes. In the long term, GP markedly reduced tumor counts and malignant conversion, along with significant decreases in mast cell infiltration, serum IgE and Eotaxin. We also found inhibition of P38 phosphorylation and reduced PCNA, Ki67 and BCL2 levels, suggesting that the anti-inflammatory effects of GP inhibits P38, acting as an upstream regulator to inhibit proliferation and reduce tumor cell survival. Together, GP appears to protect against UVB-mediated skin damage and carcinogenesis in SKH-1 mice and should be explored further as a supplement for NMSC prevention.
非黑色素瘤皮肤癌(NMSCs)是美国诊断出的最常见癌症,且在男性中更为频发。我们之前证明了膳食葡萄粉(GP)对雌性SKH-1小鼠紫外线B(UVB)介导的皮肤肿瘤发生具有化学保护作用。在此基础上进行拓展,我们在此确定了GP在雄性和雌性SKH-1小鼠短期UVB暴露方案(0%或5% GP,每隔一天进行UVB照射,持续2周)中的作用,并且通过雄性SKH-1小鼠(0%、3%或5% GP;每周进行两次UVB照射,持续28周)探究了UVB致癌过程中任何与性别相关的差异。在短期研究中,我们发现GP对两性的早期上皮增生和肥大细胞浸润均有保护作用。长期来看,GP显著减少了肿瘤数量和恶性转化,同时肥大细胞浸润、血清免疫球蛋白E(IgE)和嗜酸性粒细胞趋化因子也显著降低。我们还发现GP抑制了P38磷酸化,并降低了增殖细胞核抗原(PCNA)、Ki67和B细胞淋巴瘤2(BCL2)的水平,这表明GP的抗炎作用抑制了P38,作为上游调节因子抑制细胞增殖并降低肿瘤细胞存活率。总之,GP似乎对SKH-1小鼠UVB介导的皮肤损伤和致癌作用具有保护作用,应进一步探索其作为预防NMSCs补充剂的可能性。