Novel Approaches to Chemoprevention of Skin Cancer
Novel Approaches to Chemoprevention of Skin Cancer
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DOI：
10.1111/j.1346-8138.2000.tb02259.x
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发表时间：
2000-11
期刊：
影响因子：
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通讯作者：
D. Bickers;M. Athar
中科院分区：
文献类型：
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作者：
D. Bickers;M. Athar
防止阳光引起的损伤导致皮肤光致癌是一个非常理想的目标。在各种策略中，利用无毒药物预防癌前病变或其替代标志物发生的化学预防方法具有潜在的吸引力。流行病学和实验研究提供的证据表明，人类饮食中的一些天然化学物质可以降低癌症风险。除了水，茶是世界上最常见的饮料。红茶占茶叶总产量的近80%。红茶和绿色茶来自同一种植物，山茶花。绿色茶含有称为黄烷醇的单体多酚，红茶含有二聚黄烷醇和称为茶黄素（TF）和茶红素（TR）的聚合多酚。在过去的15年里，我们的实验室一直在探索使用茶及其成分作为预防皮肤癌方法的可行性。我们证明了绿色茶、红茶和成分多酚可以防止化学和紫外线B（UVB）诱导的致癌作用，并减少皮肤中已建立肿瘤的生长。我们还显示了绿色和红茶提取物对UVB和peptide+紫外线A（PUVA）诱导的皮肤早期损伤的功效。虽然PUVA在治疗某些皮肤疾病方面非常有效，但对患者队列的仔细随访研究表明，与UVB类似，PUVA治疗会增加皮肤鳞状细胞癌和黑色素瘤的风险。我们发现，在SKH-1小鼠治疗前和治疗期间口服标准化绿色茶提取物（SGTE）可减少PUVA诱导的皮肤增生和角化过度。SGTE处理还抑制PUVA诱导的c-fos和p53蛋白蓄积以及上皮过度增殖。PUVA治疗后局部应用和口服SGTE均可减少皮肤炎症和细胞过度增殖。在PUVA治疗前将SGTE局部应用于人皮肤可抑制延迟性皮肤炎症反应。同样，口服和局部给予标准化红茶提取物（SBTE）及其两种主要的多酚亚组分可保护SKH-1小鼠免受UVB诱导的红斑。此外，将茶提取物局部应用于人类志愿者可防止UVB诱导的红斑。总之，这些研究表明，茶提取物可有效减少UVB和PUVA介导的DNA损伤，早期反应基因的表达和皮肤的早期炎症变化。这些研究验证了采用天然膳食成分作为癌症化学预防方法的概念原理。
Protection against sun‐induced damage leading to photocarcinogenesis in skin is a highly desirable goal. Among various strategies, chemopreventive approaches utilizing non‐toxic agents to prevent the occurrence of precancerous lesions or their surrogate markers are potentially attractive. Epidemiological and experimental studies provide evidence that some naturally occurring chemical agents in the human diet can diminish cancer risk. Aside from water, tea is the most common beverage consumed worldwide. Black tea accounts for nearly 80% of total tea production. Black tea and green tea are derived from the same plant, Camelia sinensis. Green tea contains monomeric polyphenols known as flavanols and black tea contains dimeric flavanols and polymeric polyphenols known as theaflavins (TFs) and thearubigins (TRs). Over the past fifteen years our laboratory has been exploring the feasibility of using tea and its constituents as an approach to skin cancer prevention. We demonstrated that green tea, black tea and constituent polyphenols protect against chemical‐ and ultraviolet B (UVB)‐induced carcinogenesis and reduce the growth of established tumors in skin. We have also shown the efficacy of green and black tea extracts against UVB and psoralen + ultraviolet A (PUVA)‐induced early damage in skin. Although PUVA is highly effective in treating certain skin diseases, careful follow‐up studies of cohorts of patients have shown that similar to UVB, PUVA treatment increases the risk for cutaneous squamous cell carcinoma and melanoma. We have found that oral administration of a standardized green tea extract (SGTE) prior to and during treatment of SKH‐1 mice diminished PUVA‐induced skin hyperplasia and hyperkeratosis. SGTE‐treatment also inhibited PUVA‐induced accumulation of c‐fos and p53 proteins and epithelial hyperproliferation. Both topical application and oral administration of SGTE after PUVA‐treatment reduced skin inflammation and cell hyperproliferation. Topical application of SGTE to human skin prior to PUVA‐treatment inhibited the delayed skin inflammatory response. Similarly, oral and topical administration of standardized black tea extract (SBTE) and its two major polyphenolic sub‐fractions protect against UVB‐induced erythema in SKH‐1 mice. Furthermore, topical application of tea extracts to human volunteers protects against UVB‐induced erythema. In summary, these studies indicate that tea extracts are effective in reducing UVB‐ and PUVA‐mediated DNA damage, expression of early response genes and early inflammatory changes in skin. These studies verify a conceptual rationale for employing naturally occurring dietary constituents as an approach to cancer chemoprevention.