从蒌叶胡椒（胡椒科）精油中分离出的莰烯可诱导黑色素瘤细胞发生内源性凋亡，并在体内表现出抗肿瘤活性。

Camphene isolated from essential oil of Piper cernuum (Piperaceae) induces intrinsic apoptosis in melanoma cells and displays antitumor activity in vivo.

作者信息

Girola Natalia, Figueiredo Carlos R, Farias Camyla F, Azevedo Ricardo A, Ferreira Adilson K, Teixeira Sarah F, Capello Tabata M, Martins Euder G A, Matsuo Alisson L, Travassos Luiz R, Lago João H G

机构信息

Experimental Oncology Unit (UNONEX), Federal University of São Paulo, SP, Brazil.

出版信息

Biochem Biophys Res Commun. 2015 Nov 27;467(4):928-34. doi: 10.1016/j.bbrc.2015.10.041. Epub 2015 Oct 16.

DOI:10.1016/j.bbrc.2015.10.041

PMID:26471302

Abstract

Natural monoterpenes were isolated from the essential oil of Piper cernuum Vell. (Piperaceae) leaves. The crude oil and the individual monoterpenes were tested for cytotoxicity in human tumor cell lineages and B16F10-Nex2 murine melanoma cells. In the present work we demonstrate the activity of camphene against different cancer cells, with its mechanism of action being investigated in vitro and in vivo in murine melanoma. Camphene induced apoptosis by the intrinsic pathway in melanoma cells mainly by causing endoplasmic reticulum (ER) stress, with release of Ca(2+) together with HmgB1 and calreticulin, loss of mitochondrial membrane potential and up regulation of caspase-3 activity. Importantly, camphene exerted antitumor activity in vivo by inhibiting subcutaneous tumor growth of highly aggressive melanoma cells in a syngeneic model, suggesting a promising role of this compound in cancer therapy.

摘要

从胡椒属植物垂穗胡椒（Piper cernuum Vell.，胡椒科）叶片的精油中分离出天然单萜。对原油和各个单萜进行了人肿瘤细胞系和B16F10-Nex2小鼠黑色素瘤细胞的细胞毒性测试。在本研究中，我们证明了莰烯对不同癌细胞的活性，并在体外和体内对小鼠黑色素瘤研究了其作用机制。莰烯主要通过引起内质网（ER）应激，导致Ca(2+)与HmgB1和钙网蛋白一起释放、线粒体膜电位丧失以及caspase-3活性上调，通过内在途径诱导黑色素瘤细胞凋亡。重要的是，莰烯在同基因模型中通过抑制高侵袭性黑色素瘤细胞的皮下肿瘤生长在体内发挥抗肿瘤活性，表明该化合物在癌症治疗中具有广阔前景。