3'-羟基紫檀芪抑制 7,12-二甲基苯并[a]蒽（DMBA）/12-O-十四烷酰佛波醇-13-乙酸酯（TPA）诱导的小鼠皮肤癌变。
3'-Hydroxypterostilbene Inhibits 7,12-Dimethylbenz[a]anthracene (DMBA)/12-O-Tetradecanoylphorbol-13-Acetate (TPA)-Induced Mouse Skin Carcinogenesis.
机构信息
Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan.
Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan; Tsinghua Berkeley Shenzhen Institute (TBSI), Tsinghua University, Shenzhen, China.
出版信息
Phytomedicine. 2021 Jan;81:153432. doi: 10.1016/j.phymed.2020.153432. Epub 2020 Dec 3.
BACKGROUND
A natural pterostilbene analogue isolated from the herb Sphaerophysa salsula, 3'-hydroxypterostilbene (HPSB), exhibits antiproliferative activity in several cancer cell lines; however, the inhibitory effects of HPSB on skin carcinogenesis remains unclear.
PURPOSE
The aim of this study was to evaluate the inhibitory effects of HPSB on two-stage skin carcinogenesis in mice and its potential mechanism.
STUDY DESIGN AND METHODS
This study investigated the anti-inflammatory and anti-tumor effects of HPSB in the 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated acute skin inflammation and 7,12-dimethylbenz[a]anthracene (DMBA)/TPA-induced two-stage skin carcinogenesis model. In addition, the effects of HPSB on the modulation of the phase I and phase II metabolizing enzymes in the DMBA-induced HaCaT cell model were investigated.
RESULTS
The results provide evidence that topical treatment with HPSB significantly inhibits TPA-induced epidermal hyperplasia and leukocyte infiltration through the down-regulation of cyclooxygenase-2 (COX-2), matrix metalloprotein-9 (MMP-9), and ornithine decarboxylase (ODC) protein expression in mouse skin. Furthermore, HPSB suppresses DMBA/TPA-induced skin tumor incidence and multiplicity via the inhibition of proliferating cell nuclear antigen (PCNA), Cyclin B1 and cyclin-dependent kinase 1 (CDK1) expression in the two-stage skin carcinogenesis model. In addition, pretreatment with HPSB markedly reduces DMBA-induced cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1B1 (CYP1B1) gene expression in human keratinocytes; however, HPSB does not significantly affect the gene expression of the phase II enzymes.
CONCLUSION
This is the first study to show that topical treatment with HPSB prevents mouse skin tumorigenesis. Overall, our study suggests that natural HPSB may serve as a novel chemopreventive agent capable of preventing carcinogen activation and inflammation-associated tumorigenesis.
背景
从鳞球茎卷柏中分离出的天然白藜芦醇类似物 3'-羟基白藜芦醇（HPSB）在几种癌细胞系中表现出抗增殖活性；然而，HPSB 对皮肤癌变的抑制作用尚不清楚。
目的
本研究旨在评估 HPSB 对小鼠二阶段皮肤癌变的抑制作用及其潜在机制。
研究设计与方法
本研究调查了 HPSB 在 12-O-十四烷酰佛波醇-13-乙酸酯（TPA）刺激的急性皮肤炎症和 7,12-二甲基苯并[a]蒽（DMBA）/TPA 诱导的二阶段皮肤癌变模型中的抗炎和抗肿瘤作用。此外，还研究了 HPSB 对 DMBA 诱导的 HaCaT 细胞模型中 I 相和 II 相代谢酶调节的影响。
结果
研究结果表明，HPSB 局部治疗可通过下调环氧合酶-2（COX-2）、基质金属蛋白酶-9（MMP-9）和鸟氨酸脱羧酶（ODC）蛋白表达，显著抑制 TPA 诱导的小鼠皮肤表皮增生和白细胞浸润。此外，HPSB 通过抑制增殖细胞核抗原（PCNA）、细胞周期蛋白 B1 和细胞周期蛋白依赖性激酶 1（CDK1）在二阶段皮肤癌变模型中的表达，抑制 DMBA/TPA 诱导的皮肤肿瘤发生率和多发性。此外，HPSB 预处理可显著降低 DMBA 诱导的人角质细胞中细胞色素 P450 1A1（CYP1A1）和细胞色素 P450 1B1（CYP1B1）基因表达；然而，HPSB 对 II 相酶的基因表达没有显著影响。
结论
这是第一项表明局部使用 HPSB 可预防小鼠皮肤肿瘤发生的研究。总体而言，我们的研究表明，天然 HPSB 可能作为一种新型化学预防剂，能够预防致癌物激活和炎症相关的肿瘤发生。
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