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Keywords = Gukulenin A

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14 pages, 3081 KiB  
Article
Marine Sponge-Derived Gukulenin A Sensitizes Ovarian Cancer Cells to PARP Inhibition via Ferroptosis Induction
by Jin-Hyung Kim, Jung-Rae Rho and Jung-Hye Choi
Mar. Drugs 2025, 23(4), 138; https://doi.org/10.3390/md23040138 - 22 Mar 2025
Viewed by 685
Abstract
Resistance to PARP inhibitors (PARPi), such as olaparib (OLA), is a major challenge in ovarian cancer treatment. In this study, we investigated the combination effect of PARPi and gukulenin A (GUA), a bis-tropolone tetraterpenoid isolated from the marine sponge Phorbas gukhulensis. We [...] Read more.
Resistance to PARP inhibitors (PARPi), such as olaparib (OLA), is a major challenge in ovarian cancer treatment. In this study, we investigated the combination effect of PARPi and gukulenin A (GUA), a bis-tropolone tetraterpenoid isolated from the marine sponge Phorbas gukhulensis. We found that GUA at a mildly cytotoxic dose synergistically enhanced OLA-induced cytotoxicity in human ovarian cancer cells. The combination treatment significantly increased reactive oxygen species (ROS) levels and lipid peroxidation, leading to ferroptotic rather than apoptotic cell death. Network pharmacology and gene ontology (GO) enrichment analyses revealed oxidative stress-related pathways as key mediators of this effect. Inhibition of NADPH oxidase (NOX) reversed combination-induced cell death, while ferrostatin-1 (FER-1), a ferroptosis inhibitor, significantly reduced lipid peroxidation and cytotoxicity. Additionally, GUA and OLA treatment suppressed ERK1/2 activation, and ERK overexpression attenuated the combination-induced cell death. Collectively, these findings suggest that marine-derived GUA enhances PARPi efficacy in ovarian cancer cells by inducing ferroptosis through oxidative stress and ERK pathway modulation. Full article
(This article belongs to the Special Issue Discovery of Marine-Derived Anticancer Agents, 2nd Edition)
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10 pages, 2307 KiB  
Article
Anticancer Activity of Gukulenin A Isolated from the Marine Sponge Phorbas gukhulensis In Vitro and In Vivo
by Ji-Hye Ahn, Jeong-Hwa Woo, Jung-Rae Rho and Jung-Hye Choi
Mar. Drugs 2019, 17(2), 126; https://doi.org/10.3390/md17020126 - 21 Feb 2019
Cited by 14 | Viewed by 4565
Abstract
Gukulenin A is a bis-tropolone tetraterpenoid isolated from the marine sponge Phorbas gukhulensis. 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 [...] Read more.
Gukulenin A is a bis-tropolone tetraterpenoid isolated from the marine sponge Phorbas gukhulensis. 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. Full article
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