Anticancer Activity of Gukulenin A Isolated from the Marine Sponge Phorbas gukhulensis In Vitro and In Vivo

• Published in: Marine drugs Vol. 17; no. 2; p. 126
• Main Authors: Ahn, Ji-Hye, Woo, Jeong-Hwa, Rho, Jung-Rae, Choi, Jung-Hye
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.02.2019; MDPI
• Subjects: Animals; Annexin V; Anticancer properties; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Antitumor activity; Apoptosis; Apoptosis - drug effects; Cancer; Cancer therapies; Caspase 3 - metabolism; Caspase 8 - metabolism; Caspase 9 - metabolism; Caspase inhibitors; Caspase-3; Cell cycle; Cell Cycle - drug effects; Cell death; Cell Line, Tumor; Cell lines; Cell viability; Cells; Chemical compounds; Cytotoxicity; Drug dosages; Drug resistance; Female; G1 phase; gukulenin A; Humans; Leukemia; Marine invertebrates; Metabolites; Mice; Mice, Inbred BALB C; Mice, Nude; Natural products; Neoplasms; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Ovaries; Peptides; Pharmacology; Phorbas; Phorbas gukhulensis; Porifera - chemistry; Random Allocation; Terpenes - isolation & purification; Terpenes - pharmacology; Tumor cell lines; tumor xenograft model; Xenograft Model Antitumor Assays; gukulenin A; apoptosis; Phorbas gukhulensis; ovarian cancer; tumor xenograft model
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md17020126

Gukulenin A is a bis-tropolone tetraterpenoid isolated from the marine sponge . In this study, we examined the anticancer activities of gukulenin A in ovarian cancer cell lines (A2780, SKOV3, OVCAR-3, and TOV-21G) and in an ovarian cancer mouse model generated by injecting A2780 cells. We found that gukulenin A suppressed tumor growth in A2780-bearing mice. Gukulenin A markedly inhibited cell viability in four ovarian cancer cell lines, including the A2780 cell line. Gukulenin A treatment increased the fraction of cells accumulated at the sub G1 phase in a dose-dependent manner and the population of annexin V-positive cells, suggesting that gukulenin A induces apoptotic cell death in ovarian cancer cells. In addition, gukulenin A triggered the activation of caspase-3, -8, and -9, and caspase inhibitors attenuated gukulenin A-induced A2780 cell death. The results suggest that gukulenin A may be a potential therapeutic agent for ovarian cancer.