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β-Elemene inhibits 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate-induced skin tumorigenesis through suppression of NF-κB-associated signaling events in the mouse skin model.
Journal of Biochemical and Molecular Toxicology ( IF 3.6 ) Pub Date : 2020-07-14 , DOI: 10.1002/jbt.22550
Xing Hu 1 , Liang Wang 2 , Lili Zhang 3 , Tao Zhang 4
Affiliation  

β‐Elemene (1‐methyl‐1‐vinyl‐2,4‐diisopropenyl‐cyclohexane), a natural sesquiterpene‐derived curcumae radix, exhibits a variety of pharmacologic properties including anticancer. However, the molecular action of β‐elemene in chemical‐induced skin carcinogenesis remains unclear. Therefore, the present study executes to investigate a possible effect of β‐elemene in the 7,12‐dimethylbenz(a)anthracene (DMBA)/12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐promoted skin tumor model. The experimental mice were subjected to execute two‐stage skin carcinogenesis and it has been initiated by the addition of DMBA on the dorsal portion of the mouse skin. One week after, for chemical carcinogen of mice, topical exposure of DMBA has been induced following with TPA (5 nmol) in acetone (200 μL) given weekly twice for 20 weeks respectively. After completion of the experimental period, we noticed that 100% of tumor incidence, histopathological changes, decreased lipid peroxidation (LPO), and decreased antioxidant levels in DMBA/TPA‐promoted skin carcinogenesis. Furthermore, enhanced activity of inflammatory protein markers (nuclear factor [NF]‐κB, tumor necrosis factor‐α, interleukin‐6, cyclooxygenase‐2, and nitric oxide synthase) and cell‐proliferative messenger RNA markers (PCNA, cyclin D1), and increased antiapoptotic protein Bcl‐2; decreased proapoptotic protein marker events Bax and caspase 3 and 9 expressions were noticed in DMBA/TPA promoted skin tissue. In this study, we noticed that β‐elemene noticeably reversed the histopathological changes and antioxidant levels in tumor‐bearing mice. Conversely, β‐elemene effectively inhibits inflammation, cell proliferation events, and enhances proapoptotic factors, by suppression of NF‐κB transcriptional activation in DMBA/TPA animals. Thus, we concluded that β‐elemene prevents DMBA/TPA promoted skin carcinogenesis through its antioxidant and abate inflammation markers and cell‐proliferative markers also activating proapoptotic molecules.

中文翻译:

β-榄香烯通过抑制小鼠皮肤模型中与NF-κB相关的信号传导事件,抑制了7,12-二甲基苯并(a)蒽/ 12-O-十四烷酰phorbol-13-乙酸盐诱导的皮肤肿瘤发生。

β-榄香烯(1-甲基-1-乙烯基-2,4-二异丙烯基-环己烷)是一种天然的倍半萜烯衍生的姜黄基,具有多种药理特性,包括抗癌性。然而,β-榄香烯在化学诱导的皮肤癌变中的分子作用仍不清楚。因此,本研究旨在研究β-榄香烯在7,12-二甲基苯并(a)蒽(DMBA)/ 12-o-十四烷酰佛波-13-乙酸(TPA)促进的皮肤肿瘤模型中的可能作用。实验小鼠经历了两阶段的皮肤癌变,这是通过在小鼠皮肤的背部添加DMBA来引发的。一周后,对于小鼠的化学致癌物,在丙酮(200μL)中的TPA(5 nmol)每周两次分别给药20周后,已引起DMBA局部暴露。实验期结束后,我们注意到DMBA / TPA促进皮肤癌变的100%肿瘤发生率,组织病理学变化,脂质过氧化(LPO)降低和抗氧化剂水平降低。此外,炎症蛋白标记(核因子[NF]-κB,肿瘤坏死因子-α,白介素-6,环氧合酶-2和一氧化氮合酶)和细胞增殖信使RNA标记(PCNA,细胞周期蛋白D1)的活性增强,并增加抗凋亡蛋白Bcl-2;在DMBA / TPA促进的皮肤组织中发现了促凋亡蛋白标记物事件的降低Bax和caspase 3和9表达。在这项研究中,我们注意到β-榄香烯明显逆转了荷瘤小鼠的组织病理学变化和抗氧化剂水平。相反,β-榄香烯有效抑制炎症,细胞增殖事件,通过抑制DMBA / TPA动物中的NF-κB转录激活来增强凋亡因子。因此,我们得出结论,β-榄香烯通过其抗氧化剂和减轻的炎症标志物以及还可以激活促凋亡分子的细胞增殖标志物来阻止DMBA / TPA促进皮肤癌发生。
更新日期:2020-07-14
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