Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi-110062, India.
J Appl Toxicol. 2013 Aug;33(8):828-37. doi: 10.1002/jat.2739. Epub 2012 Jul 4.
Geraniol (GOH), a naturally occurring monoterpene, has been shown to have antiproliferative, cell cycle arrest and apoptosis-inducing effects, and represents a promising cancer chemopreventive agent. In the present study, we investigated the chemopreventive potential of GOH (50 and 100 mg kg(-1) body weight) against 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol 13-acetate (TPA)-mediated skin tumorigenesis in Swiss albino mice. The topical treatment of GOH, 30 min prior to TPA (2 µg per 200 µl of acetone) treatment significantly inhibited TPA-induced skin edema, hyperplasia, COX-2 induction and oxidative stress response. The GOH treatment also resulted in reduction of TPA-induced ornithine decarboxylase activity and [(3) H] thymidine incorporation by 53% (P < 0.001) and 41% (P < 0.001), respectively. We found that GOH treatment significantly inhibited the tumor incidence and number of tumors (P < 0.001) and extended the latency period from 4 weeks in DMBA/TPA treatment group to 10 weeks in GOH-pretreated mice. Furthermore, we observed that GOH treatment significantly suppressed the Ras/Raf/ERK1/2 signaling pathway in skin tumor. Consistently, GOH-treated skin tumors showed reduced expression of Bcl-2 and increased expression of Bax in these lesions. Thus, it was concluded that GOH inhibits DMBA/TPA-mediated skin tumorigenesis by attenuating the Ras proliferation pathway and inducing pro-apoptotic state via inhibition of oxidative stress response and inflammation.
香叶醇（GOH）是一种天然存在的单萜烯，已被证明具有抗增殖、细胞周期停滞和诱导细胞凋亡的作用，是一种有前途的癌症化学预防剂。在本研究中，我们研究了 GOH（50 和 100mg/kg 体重）对 7,12-二甲基苯并[a]蒽（DMBA）/12-O-十四烷酰佛波醇 13-乙酸酯（TPA）介导的瑞士白化小鼠皮肤肿瘤发生的化学预防潜力。GOH 的局部治疗，在 TPA（2μl 丙酮中的 200μl）处理前 30 分钟，显著抑制了 TPA 诱导的皮肤水肿、增生、COX-2 诱导和氧化应激反应。GOH 处理还导致 TPA 诱导的鸟氨酸脱羧酶活性和[（3）H]胸苷掺入分别减少 53%（P<0.001）和 41%（P<0.001）。我们发现 GOH 处理显著抑制肿瘤发生率和肿瘤数量（P<0.001），并将潜伏期从 DMBA/TPA 处理组的 4 周延长至 GOH 预处理小鼠的 10 周。此外，我们观察到 GOH 处理显著抑制了皮肤肿瘤中的 Ras/Raf/ERK1/2 信号通路。一致地，GOH 处理的皮肤肿瘤显示出 Bcl-2 表达减少和 Bax 表达增加。因此，我们得出结论，GOH 通过抑制 Ras 增殖途径和通过抑制氧化应激反应和炎症诱导促凋亡状态来抑制 DMBA/TPA 介导的皮肤肿瘤发生。
