Effects of 3-styrylchromones on metabolic profiles and cell death in oral squamous cell carcinoma cells

Hiroshi Sakagami, Chiyako Shimada, Yumiko Kanda, Osamu Amano, Masahiro Sugimoto, Sana Ota, Tomoyoshi Soga, Masaru Tomita, Akira Sato, Sei ichi Tanuma, Koichi Takao, Yoshiaki Sugita

研究成果: Article

31 引用 (Scopus)

抜粋

4H-1-benzopyran-4-ones (chromones) are important naturally-distributing compounds. As compared with flavones, isoflavones and 2-styrylchromones, there are only few papers of 3-styrylchromones that have been published. We have previously reported that among fifteen 3-styrylchromone derivatives, three new synthetic compounds that have OCH3 group at the C-6 position of chromone ring, (E)-3-(4-hydroxystyryl)-6-methoxy-4H-chromen-4-one (compound 11), (E)-6-methoxy-3-(4-methoxystyryl)-4H-chromen-4-one (compound 4), (E)-6-methoxy-3-(3,4,5-trimethoxystyryl)-4H-chromen-4-one (compound 6) showed much higher cytotoxicities against four epithelial human oral squamous cell carcinoma (OSCC) lines than human normal oral mesenchymal cells. In order to further confirm the tumor specificities of these compounds, we compared their cytotoxicities against both human epithelial malignant and non-malignant cells, and then investigated their effects on fine cell structures and metabolic profiles and cell death in human OSCC cell line HSC-2. Cytotoxicities of compounds 4, 6, 11 were assayed with MTT method. Fine cell structures were observed under transmission electron microscope. Cellular metabolites were extracted with methanol and subjected to CE-TOFMS analysis. Compounds 4, 6, 11 showed much weaker cytotoxicity against human oral keratinocyte and primary human gingival epithelial cells, as compared with HSC-2, confirming their tumor-specificity, whereas doxorubicin and 5-FU were highly cytotoxic to these normal epithelial cells, giving unexpectedly lower tumor-specificity. The most cytotoxic compound 11, induced the mitochondrial vacuolization, autophagy suppression followed by apoptosis induction, and changes in the metabolites involved in amino acid and glycerophospholipid metabolisms. Chemical modification of lead compound 11 may be a potential choice for designing new type of anticancer drugs.

元の言語English
ページ(範囲)1281-1290
ページ数10
ジャーナルToxicology Reports
2
DOI
出版物ステータスPublished - 2015 12 1

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

フィンガープリント Effects of 3-styrylchromones on metabolic profiles and cell death in oral squamous cell carcinoma cells' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

  • これを引用

    Sakagami, H., Shimada, C., Kanda, Y., Amano, O., Sugimoto, M., Ota, S., Soga, T., Tomita, M., Sato, A., Tanuma, S. I., Takao, K., & Sugita, Y. (2015). Effects of 3-styrylchromones on metabolic profiles and cell death in oral squamous cell carcinoma cells. Toxicology Reports, 2, 1281-1290. https://doi.org/10.1016/j.toxrep.2015.09.009