C11 cyclopentenone from the ascidian Diplosoma sp. prevents epidermal growth factor-induced transformation of JB6 cells

C11 cyclopentenone, 5-hydroxy-7-prop-2-en- (E)-ylidene-7,7a-dihydro-2H-cyclopenta[b] pyran-6-one, isolated earlier from the sponges and ascidians, is known as a natural product possessing antimicrobial and cytotoxic properties. However, its cancer preventive activity has not been studied. Cancer preventive and proapoptotic properties of the compound as well as its effect on the main Mitogen- Activated Protein-Kinase (MAPK) signaling pathways were examined by the methods of epidermal growth factor- induced (EGFinduced) JB6 Cl41 P+ cell transformation in soft agar, flow cytometry, and MTS test of cell viability. Results: the compound inhibits EGFinduced neoplastic JB6 Cl41 P+ cell transformation in soft agar and induces apoptosis of HL-60 and THP-1 human leukemia cells. Jun N-terminal Kinase and p38 MAPK signaling pathways are involved in the cellular response to the treatment by the compound. Conclusions: 5-hydroxy-7-prop-2-en-(E)-ylidene- 7,7a-dihydro-2H-cyclopenta[b]pyran-6- one and other related marine C11 cyclopentenones have potential for development of a new antitumor agent in cancer prophylactics and should be further investigated.