Effect of the orthoquinone moiety in 9,10-phenanthrenequinone on its ability to induce apoptosis in HCT-116 and HL-60 cells

Noriyuki Hatae, Jun Nakamura, Tetsuo Okujima, Minoru Ishikura, Takumi Abe, Satoshi Hibino, Tominari Choshi, Chiaki Okada, Hiroko Yamada, Hidemitsu Uno, Eiko Toyota

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4637-4640
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number16
DOIs
Publication statusPublished - Aug 15 2013
Externally publishedYes

Keywords

  • 9,10-Phenanthrenequinone
  • Antitumor activity
  • Apoptosis
  • Diesel exhaust particulates
  • Orthoquinone

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Effect of the orthoquinone moiety in 9,10-phenanthrenequinone on its ability to induce apoptosis in HCT-116 and HL-60 cells'. Together they form a unique fingerprint.

Cite this