Lee Brigette, Bohmann Jonathan, Reeves Tony, Levenson Corey, Risinger April L
†Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas 78229, United States.
‡Southwest Research Institute, 6220 Culebra Road, San Antonio, Texas 78238, United States.
J Nat Prod. 2015 Jun 26;78(6):1357-62. doi: 10.1021/acs.jnatprod.5b00207. Epub 2015 May 20.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with no major advancements in treatment over the past 40 years. The current study explores the biological effects of East Indian sandalwood oil (EISO) and its two major constituents, α- and β-santalol, against a variety of HNSCC lines. All three agents exhibited cytotoxic effects and caused accumulation of cells in the G2/M phases of the cell cycle. Additionally, treatment with these agents caused formation of multipolar mitotic spindles similar to those observed upon treatment of cells with compounds that affect microtubule polymerization. Indeed, the santalols, as well as EISO, inhibited the polymerization of purified tubulin, indicating for the first time that these compounds have the ability to directly bind to tubulin and affect microtubule formation. Modeling studies suggest that the santalols can weakly bind to the colchicine site on tubulin, and topical administration of EISO to a HNSCC xenograft inhibited tumor growth with no observed toxicities. Therefore, santalols can directly interact with tubulin to inhibit the polymerization of microtubules, similarly to established classes of chemotherapeutic agents, albeit with greatly reduced potency that is not associated with the classic toxicity associated with most other compounds that interact directly with tubulin.
头颈部鳞状细胞癌（HNSCC）是全球第六大常见癌症，在过去40年中治疗方面没有重大进展。当前的研究探讨了东印度檀香油（EISO）及其两种主要成分α-檀香醇和β-檀香醇对多种HNSCC细胞系的生物学效应。这三种物质均表现出细胞毒性作用，并导致细胞在细胞周期的G2/M期积累。此外，用这些物质处理会导致形成多极有丝分裂纺锤体，类似于用影响微管聚合的化合物处理细胞时观察到的情况。实际上，檀香醇以及EISO抑制了纯化微管蛋白的聚合，首次表明这些化合物有能力直接结合微管蛋白并影响微管形成。建模研究表明，檀香醇可与微管蛋白上的秋水仙碱位点弱结合，将EISO局部应用于HNSCC异种移植瘤可抑制肿瘤生长，且未观察到毒性。因此，檀香醇可直接与微管蛋白相互作用以抑制微管聚合，类似于已确立的化疗药物类别，尽管效力大大降低，且与大多数其他直接与微管蛋白相互作用的化合物相关的典型毒性无关。
