Abstract |
9,10-Phenanthrenequinone (9,10-PQ) is one of the most abundant quinones among diesel exhaust particulates. Recent data have suggested that quinones induce apoptosis in immune, epithelial and tumor cells, leading to respirator illness; however, the mechanisms by which quinones induce apoptosis and the structure required for this remain unknown. We studied the antitumor activity of 9,10-PQ analogs against two human tumor cell lines, HCT-116 colon tumor cells and HL-60 promyelocytic leukemia cells. The loss of the cis-orthoquinone unit in 9,10-PQ abrogated its ability to induce apoptosis in the two tumor cell lines, and the LC50 values of these analogs were indicated over 10 μM. An analog of 9,10-PQ in which the biaryl unit had been deleted displayed a reduced ability to induce tumor cell apoptosis, while the analogs 1,10-phenanthroline-5,6-dione (9) and pyrene-4,5-dione (10), which also had modified biaryl units, exhibited increased tumor cell apoptotic activity. The cis-orthoquinone unit in 9,10-PQ was identified as essential for its ability to induce apoptosis in tumor cells, and its biaryl unit is also considered to influence orthoquinone-mediated apoptotic activity.
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Authors | Noriyuki Hatae, Jun Nakamura, Tetsuo Okujima, Minoru Ishikura, Takumi Abe, Satoshi Hibino, Tominari Choshi, Chiaki Okada, Hiroko Yamada, Hidemitsu Uno, Eiko Toyota |
Journal | Bioorganic & medicinal chemistry letters
(Bioorg Med Chem Lett)
Vol. 23
Issue 16
Pg. 4637-40
(Aug 15 2013)
ISSN: 1464-3405 [Electronic] England |
PMID | 23816373
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2013 Elsevier Ltd. All rights reserved. |
Chemical References |
- Antineoplastic Agents
- Phenanthrenes
- 9,10-phenanthrenequinone
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Topics |
- Antineoplastic Agents
(chemical synthesis, chemistry, pharmacology)
- Apoptosis
(drug effects)
- HCT116 Cells
- HL-60 Cells
- Humans
- Inhibitory Concentration 50
- Molecular Structure
- Neoplasms
(drug therapy)
- Phenanthrenes
(chemical synthesis, chemistry, pharmacology)
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