Department of Physiology and Pharmacology, Sapienza University, 00185 Rome, Italy.
Mutat Res. 2010 Jun 17;699(1-2):23-8. doi: 10.1016/j.mrgentox.2010.04.008. Epub 2010 Apr 14.
beta-Caryophyllene is a bi-cyclic sesquiterpene that occurs in essential oils from several plants. A variety of biological activities have been ascribed to this compound. In particular, it seems to possess anti-carcinogenic properties, due to its capability to induce detoxifying enzymes or to enhance, in vitro and in vivo, the natural killer cell-induced cytotoxicity against tumours. Conversely, the knowledge on the DNA-damaging activity of the substance and its modulation is scanty. Therefore, in this study, we aimed at evaluating the capability of beta-caryophyllene to protect cultured human lymphocytes from the genotoxic damage induced by ethyl methanesulfonate (EMS) and colcemid (COL) in the micronucleus assay. To investigate the mechanisms of action of this sesquiterpene, the cultures were treated with the compound before (pre-treatment), during (co-treatment) and after (post-treatment) treatment with the mutagens. Up to 100 microg/ml, beta-caryophyllene by itself did not produce any cytotoxic and genotoxic effect, as shown by the value of the nuclear division index (NDI) and the frequency of micronuclei (MN). The test compound (0.1-100 microg/ml) significantly reduced the MN frequency induced by EMS in pre- and co-treatment protocols (up to 64.4% and 87% reduction, respectively). In the post-treatment protocol, beta-caryophyllene was not effective as an antimutagen. No significant reduction of COL-induced MN frequency was found. The antigenotoxic activity of beta-caryophyllene observed here suggests that this compound could act by chemical interaction with the mutagen in the growth medium (co-treatment) or in the cytoplasm of lymphocytes (pre-treatment), so acting as a desmutagen. These data encourage further studies to investigate the mode of action and the potential use of this compound as a chemopreventive agent.
β-石竹烯是一种双环倍半萜烯，存在于几种植物的精油中。该化合物具有多种生物活性。特别是，它似乎具有抗癌特性，因为它能够诱导解毒酶，或体外和体内增强自然杀伤细胞对肿瘤的细胞毒性。相反，关于该物质的致DNA 损伤活性及其调节的知识很少。因此，在这项研究中，我们旨在评估β-石竹烯在微核试验中保护培养的人淋巴细胞免受乙基甲磺酸（EMS）和秋水仙素（COL）诱导的遗传毒性损伤的能力。为了研究该倍半萜烯的作用机制，在处理诱变剂之前（预处理）、期间（共同处理）和之后（后处理）用该化合物处理培养物。β-石竹烯本身在高达 100μg/ml 的浓度下不会产生任何细胞毒性和遗传毒性作用，这可以通过核分裂指数（NDI）和微核（MN）的频率值来证明。该测试化合物（0.1-100μg/ml）在预处理和共同处理方案中显著降低了 EMS 诱导的 MN 频率（分别降低了 64.4%和 87%）。在后处理方案中，β-石竹烯作为抗诱变剂无效。COL 诱导的 MN 频率没有明显降低。β-石竹烯观察到的抗原毒性活性表明，该化合物可以通过与生长培养基中的诱变剂（共同处理）或淋巴细胞细胞质中的诱变剂（预处理）进行化学相互作用而发挥作用，从而充当脱诱变剂。这些数据鼓励进一步研究该化合物作为化学预防剂的作用方式和潜在用途。
