Growth-inhibitory effects of coumarin (1,2-benzopyrone) and 7-hydroxycoumarin on human malignant cell lines in vitro

• Published in: Journal of cancer research and clinical oncology Vol. 120 Suppl; p. S3
• Main Authors: Marshall, M E, Kervin, K, Benefield, C, Umerani, A, Albainy-Jenei, S, Zhao, Q, Khazaeli, M B
• Format: Journal Article
• Language: English
• Published: Germany 01.01.1994
• Subjects: Apoptosis - drug effects; Cell Division - drug effects; Cell Survival - drug effects; Coumarins - pharmacology; DNA, Neoplasm - biosynthesis; DNA, Neoplasm - drug effects; Dose-Response Relationship, Drug; Humans; Prostate-Specific Antigen - biosynthesis; Prostate-Specific Antigen - drug effects; Protein Biosynthesis; Proteins - drug effects; RNA, Neoplasm - biosynthesis; RNA, Neoplasm - drug effects; Time Factors; Tumor Cells, Cultured; Umbelliferones - pharmacology
• ISSN: 0171-5216
• DOI: 10.1007/bf01377114

Coumarin (1,2-benzopyrone) is a natural substance that has shown antitumor activity in vivo. The major human metabolite of coumarin, 7-hydroxycoumarin (7-HC), is the active form of the drug. While the exact mechanism(s) of action of coumarin is unknown, it has been shown previously that this drug possesses immunomodulatory activity in vitro and in vivo. The present investigations examined the direct (non-immunological) antitumor effects of coumarin and 7-HC in vitro. Both coumarin and 7-HC were found to be growth-inhibitory (cytostatic) for the following human malignant cell lines: A549, ACHN, Caki-2, Dakiki, HS-Sultan, H727, HCT-15, HL-60, K562, LNCaP, PC-3, Du 145 COLO-232, MCF-7 and RP-1788. The growth inhibition was dependent on dose and time and was reversible upon removal of cells from medium containing the drug. Coumarin and 7-HC inhibited [3H]thymidine, [3H]uridine and [3H]leucine incorporation. In a similar fashion, coumarin and 7-HC inhibited the intracellular production of prostate-specific antigen by LNCaP cells. Coumarin and 7-HC stimulated apoptosis in HL-60 cells but not in other cell lines tested. It is concluded that coumarin and 7-HC have direct antitumor (cytostatic) activity as well as immunomodulatory activity. Further information is needed in order to determine which activities are responsible for antitumor activity in vivo.