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

Marine Drugs ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 126 ◽  
Author(s):  
Ji-Hye Ahn ◽  
Jeong-Hwa Woo ◽  
Jung-Rae Rho ◽  
Jung-Hye Choi

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.

2010 ◽  
Vol 4 (S2) ◽  
Author(s):  
Fernanda Silva ◽  
Jacinta Serpa ◽  
Germana Domingues ◽  
Gabriela Silva ◽  
António Almeida ◽  
...  

2015 ◽  
Vol 22 (4) ◽  
pp. 577-591 ◽  
Author(s):  
Lingqin Yuan ◽  
Xiugui Sheng ◽  
Adam K Willson ◽  
Dario R Roque ◽  
Jessica E Stine ◽  
...  

Glutamine is one of the main nutrients used by tumor cells for biosynthesis. Therefore, targeted inhibition of glutamine metabolism may have anti-tumorigenic implications. In the present study, we aimed to evaluate the effects of glutamine on ovarian cancer cell growth. Three ovarian cancer cell lines, HEY, SKOV3, and IGROV-1, were assayed for glutamine dependence by analyzing cytotoxicity, cell cycle progression, apoptosis, cell stress, and glucose/glutamine metabolism. Our results revealed that administration of glutamine increased cell proliferation in all three ovarian cancer cell lines in a dose dependent manner. Depletion of glutamine induced reactive oxygen species and expression of endoplasmic reticulum stress proteins. In addition, glutamine increased the activity of glutaminase (GLS) and glutamate dehydrogenase (GDH) by modulating the mTOR/S6 and MAPK pathways. Inhibition of mTOR activity by rapamycin or blocking S6 expression by siRNA inhibited GDH and GLS activity, leading to a decrease in glutamine-induced cell proliferation. These studies suggest that targeting glutamine metabolism may be a promising therapeutic strategy in the treatment of ovarian cancer.


2017 ◽  
Vol 95 (6) ◽  
pp. 616-627 ◽  
Author(s):  
Behzad Bahmani ◽  
Mohammad Keyvanloo Shahrestanaki ◽  
Mustafa Ghanadian ◽  
Sima Hajiahmadi ◽  
Mahmoud Aghaei

We investigated the molecular mechanism of apoptosis induced by novel jatropha-6(17),11E-diene class derivatives, compounds A, B, and C that were extracted from Euphorbia osyridea Boiss, in the ovarian cancer cell lines Caov-4 and OVCAR-3. The OVCAR-3 and Caov-4 cell lines were treated with different concentrations of these compounds. Cytotoxicity was evaluated using MTT, clonogenic survival assay, and flow cytometry assays. The production of reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), and the activity of caspase 3 and 9 were evaluated. Compounds A, B, and C reduced cell viability in a dose-dependent manner (P < 0.05). The IC50 values were calculated as 46.27 ± 3.86, and 38.81 ± 3.30 μmol/L for compound A, 36.48 ± 3.18 and 42.59 ± 4.50 μmol/L for compound B, and 85.86 ± 6.75 and 75.65 ± 2.56 μmol/L for compound C against the Caov-4 and OVCAR-3 cell lines, respectively. Apoptosis evaluation showed that jatrophane derivatives increase both early and late apoptosis (P < 0.01). These compounds also increased ROS generation, ΔΨm, and the activity of caspase 3 and 9 in the treated cells. These results showed that compounds A and B have significant inhibitory effects on OVCAR-3 and Caov-4 proliferation and induction of apoptosis.


2020 ◽  
Author(s):  
Caroline Ukwade ◽  
Osaretin Ebuehi ◽  
Rashidat Adisa ◽  
Santos Singh ◽  
Rajesh Singh

Abstract Background: Ovarian cancer is one of the most lethal tumors of gynecologic malignancies, due to lack of early detection, and a high rate of metastasis. The standard treatment is surgery and cytotoxic chemotherapy, but due to its cost and side effects, medicinal plants are widely used in developing countries. Byrsocarpus coccineus plant preparation, has been administered to patients traditionally in the management of tumour in Nigeria. In this study, we investigated the anti-proliferative effects of B. coccineus ethanol leaf extract against OVCAR3 and SW626 ovarian cancer cell lines. After treatment of the two cell lines with the extracts, analyses were carried out to determine inhibition of proliferation and expression of cell cycle markers, pro-apoptotic and anti-apoptotic markers. Results: Results showed that B. coccineus ethanol leaf extract, significantly inhibited cell migration and colony formation in OVCAR3 and SW626 treated cells in a dose-dependent manner. Results also show that B. coccineus ethanol leaf extract modulated the expression of p53 gene, cell cycle progression, anti-apoptotic and pro-apoptotic genes. Conclusions: These results suggest that B. coccineus have anti-proliferative properties and could induce apoptosis. Further investigation will be carried out to isolate bioactive compounds for the treatment of ovarian cancer.


2021 ◽  
Author(s):  
Tatsuya Kobayashi ◽  
Akira Mitsuhashi ◽  
Piao Hongying ◽  
Masashi Shioya ◽  
Kyoko Nishikimi ◽  
...  

Abstract Purpose: Bexarotene is selectively activates retinoid X recepto, whichr is a commonly used anticancer agent for cutaneous T-cell lymphoma. In this study, we aimed to investigate the anticancer effect of bexarotene and its underlying mechanism in ovarian cancer in vitro.Methods: The ES2 and NIH:OVACAR3 ovarian cancer cell lines were treated with 0, 5, 10, or 20 µM bexarotene. After 24 hours, cell number measurement and lactate dehydrogenase (LDH) cytotoxicity assay were performed. The effect of bexarotene on CDKN1A expression, pyroptosis, and apoptosis were evaluated.Results: Bexarotene reduced cell proliferation in all concentrations in both cells. At concentrations above 10 µM, it increased extracellular LDH activity with cell rupture. In both cells, 10 µM bexarotene treatment increased the CDKN1A mRNA levels and reduced cell cycle related protein expression. In ES2 cells, caspase-4 and GSDME were activated, whereas caspase-3 was not, indicating that bexarotene-induced cell death might be pyroptosis. Conclusion: A clinical setting dose of bexarotene induced cell cycle arrest and cell death through caspase-4–mediated pyroptosis in ovarian cancer cell lines. Thus, bexarotene may serve as a novel therapeutic agent for ovarian cancer.


2020 ◽  
Vol 31 (19) ◽  
pp. 195101 ◽  
Author(s):  
Mohammad A Obeid ◽  
Siti Aisya S Gany ◽  
Alexander I Gray ◽  
Louise Young ◽  
John O Igoli ◽  
...  

Oncogene ◽  
2008 ◽  
Vol 27 (19) ◽  
pp. 2737-2745 ◽  
Author(s):  
H Sasaki ◽  
J Hayakawa ◽  
Y Terai ◽  
M Kanemura ◽  
A Tanabe-Kimura ◽  
...  

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