Search for New Type of Anticancer Drugs with High Tumor Specificity and Less Keratinocyte Toxicity

Most current anticancer drugs have shown excellent therapeutic effects on human oral squamous cell carcinoma (OSCC), but they also produce potent cytotoxicity in normal oral keratinocytes. This review article summarizes our extensive research of tumor specificity and keratinocyte toxicity of nine gr...

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Bibliographic Details
Published in:Anticancer research 2017-11, Vol.37 (11), p.5919
Main Authors: Sugita, Yoshiaki, Takao, Koichi, Uesawa, Yoshihiro, Sakagami, Hiroshi
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
Carcinoma, Squamous Cell - drug therapy
Carcinoma, Squamous Cell - pathology
Humans
Keratinocytes - cytology
Keratinocytes - drug effects
Mouth Neoplasms - drug therapy
Mouth Neoplasms - pathology
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Summary:Most current anticancer drugs have shown excellent therapeutic effects on human oral squamous cell carcinoma (OSCC), but they also produce potent cytotoxicity in normal oral keratinocytes. This review article summarizes our extensive research of tumor specificity and keratinocyte toxicity of nine groups of compounds synthesized in our laboratory. Among a total of 133 compounds, (E)-3-[2-(4-hydroxyphenyl)ethenyl]-6-methoxy-4H-1-benzopyran-4-one [ ] (classified as 3-styrylchromones), (E)-3-[2-(4-chlorophenyl)ethenyl]-7-methoxy-2H-1-benzopyran [4] (classified as 3-styryl-2H-chromenes) showed the highest tumor specificity with the least keratinocyte toxicity. Compound [ ] induced apoptotic cell death in a human OSCC cell line, possibly by down-regulating the glycerophospholipid pathway. Quantitative structure-activity relationship analysis demonstrated that the tumor specificities of [ ] and [ ] were well correlated with chemical descriptors related to their molecular size and lipophilicity. Chemical modification of these lead compounds by introduction of appropriate functional groups is a crucial step towards manufacturing new types of anticancer drugs with reduced keratinocyte toxicity.
ISSN:0250-7005
1791-7530
DOI:10.21873/anticanres.12038