3-O-Methylfunicone, a secondary metabolite produced by Penicillium pinophilum, induces growth arrest and apoptosis in HeLa cells

• Published in: Cell proliferation Vol. 37; no. 6; pp. 413 - 426
• Main Authors: Buommino, E., Nicoletti, R., Gaeta, G. M., Orlando, M., Ciavatta, M. L., Baroni, A., Tufano, M. A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.12.2004
• Subjects: Annexin A5 - metabolism; Antineoplastic Agents - toxicity; Apoptosis - drug effects; Apoptosis - physiology; Cell Cycle - drug effects; Cell Cycle - physiology; Cell Cycle Proteins - genetics; Cell Division - drug effects; Cell Division - physiology; Cyclin D1 - genetics; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinases - genetics; Cytotoxins - toxicity; DNA Fragmentation - drug effects; DNA Fragmentation - physiology; Drug Screening Assays, Antitumor; Growth Inhibitors - toxicity; HeLa Cells; Humans; Microtubules - drug effects; Microtubules - metabolism; Molecular Structure; Original; Penicillium - metabolism; Proto-Oncogene Proteins - genetics; Pyrones - toxicity; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Tubulin - drug effects; Tubulin - metabolism
• ISSN: 0960-7722; 1365-2184
• DOI: 10.1111/j.1365-2184.2004.00323.x

.  3‐O‐Methylfunicone (OMF) is a secondary metabolite produced by the soil fungus Penicillium pinophilum which has cytostatic properties. The aim of this study was to investigate the mechanisms by which such properties are exerted, with special reference to any anti‐proliferative and apoptotic potential, on HeLa cells. OMF treatment caused about 44% inhibition of cell growth after 24 h, and modifications in the tubulin fibre organization. In addition, a significant increase in p21 mRNA expression and a decrease in cyclin D1 and Cdk4 mRNA expression resulted at the same time. Apoptosis induction was demonstrated by the annexin V assay, cytofluorimetric analysis of the DNA content of the sub‐G1 fraction and DNA laddering. Taken together, our data showed that the compound inhibits proliferation of HeLa cells by several mechanisms, such as disruption of tubulin fibres, cell cycle arrest and apoptosis induction. The capacity of the compound to affect the cell cycle and to modulate apoptosis is indicative of a potential for the development of a new agent for cancer chemotherapy.