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α- and β-Santalols Directly Interact with Tubulin and Cause Mitotic Arrest and Cytotoxicity in Oral Cancer Cells.
- Source :
-
Journal of natural products [J Nat Prod] 2015 Jun 26; Vol. 78 (6), pp. 1357-62. Date of Electronic Publication: 2015 May 20. - Publication Year :
- 2015
-
Abstract
- 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.
- Subjects :
- Antineoplastic Agents chemistry
Apoptosis drug effects
Cell Cycle drug effects
Cell Division drug effects
Colchicine pharmacology
G2 Phase drug effects
Humans
Microtubules drug effects
Mitosis drug effects
Models, Molecular
Molecular Structure
Polycyclic Sesquiterpenes
Sesquiterpenes chemistry
Stereoisomerism
Antineoplastic Agents pharmacology
Mouth Neoplasms drug therapy
Santalum chemistry
Sesquiterpenes pharmacology
Tubulin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1520-6025
- Volume :
- 78
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of natural products
- Publication Type :
- Academic Journal
- Accession number :
- 25993496
- Full Text :
- https://doi.org/10.1021/acs.jnatprod.5b00207