Cytotoxicity of lapachol, β-lapachone and related synthetic 1,4-naphthoquinones against oesophageal cancer cells.

Abstract

Naphthoquinones have been found to have a wide range of biological activities, including cytotoxicity to cancer cells. The secondary metabolites lapachol, α- and β-lapachone and a series of 25 related synthetic 1,4-naphthoquinones were screened against the oesophageal cancer cell line (WHCO1). Most of the compounds exhibited enhanced cytotoxicity (IC50 1.6-11.7 μM) compared to the current drug of choice cisplatin (IC50 = 16.5 μM). This study also established that the two new synthetic halogenated compounds 12a and 16a (IC50 = 3.0 and 7.3 μM) and the previously reported compound 11a (IC50 = 3.9 μM), were non-toxic to NIH3T3 normal fibroblast cells. Cell death of oesophageal cancer cells by processes involving PARP cleavage caused by 11a was shown to be associated with elevated c-Jun levels, suggesting a role for this pathway in the mechanism of action of this cohort of naphthoquinone compounds.

• Authors: Suthananda N Sunassee, Clinton G L Veale, Nelusha Shunmoogam-Gounden, Omalaja Osoniyi, Denver T Hendricks, Mino R Caira, Jo-Anne de la Mare, Adrienne L Edkins, Antônio V Pinto, Eufrânio N da Silva Júnior, Michael T Davies-Coleman
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 62 Pg. 98-110 (Apr 2013) ISSN: 1768-3254 [Electronic] France
• PMID: 23353747 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Naphthoquinones
• beta-lapachone
• lapachol
• 1,4-naphthoquinone

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Death (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Crystallography, X-Ray
• Dose-Response Relationship, Drug
• Esophageal Neoplasms (drug therapy, pathology)
• Humans
• Mice
• Models, Molecular
• Molecular Structure
• NIH 3T3 Cells
• Naphthoquinones (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship