Jatropha-6(17),11E-diene class derivatives induce apoptosis effects in OVCAR-3 and Caov-4 ovarian cancer cell lines via a mitochondrial pathway

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.

Toxins ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 237 ◽  
Author(s):  
Okiemute Rosa Johnson-Ajinwo ◽  
Alan Richardson ◽  
Wen-Wu Li

Ovarian cancer ranks amongst the deadliest cancers in the gynaecological category of cancers. This research work aims to evaluate in vitro anti-ovarian cancer activities and identify phytochemical constituents of a rarely explored plant species—Rutidea parviflora DC. The aqueous and organic extracts of the plant were evaluated for cytotoxicity using sulforhodamine B assay in four ovarian cancer cell lines and an immortalized human ovarian epithelial (HOE) cell line. The bioactive compounds were isolated and characterized by gas/liquid chromatography mass spectrometry and nuclear magnetic resonance spectroscopy. Caspase 3/7 activity assay, western blotting and flow cytometry were carried out to assess apoptotic effects of active compounds. The extracts/fractions of R. parviflora showed promising anti-ovarian cancer activities in ovarian cancer cell lines. A principal cytotoxic alkaloid was identified as palmatine whose IC50 was determined as 5.5–7.9 µM. Palmatine was relatively selective towards cancer cells as it was less cytotoxic toward HOE cells, also demonstrating interestingly absence of cross-resistance in cisplatin-resistant A2780 cells. Palmatine further induced apoptosis by increasing caspase 3/7 activity, poly-ADP-ribose polymerase cleavage, and annexin V and propidium iodide staining in OVCAR-4 cancer cells. Our studies warranted further investigation of palmatine and R. parviflora extracts in preclinical models of ovarian cancer.


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.


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.


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.


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 ◽  
...  

2017 ◽  
Vol 37 (4) ◽  
Author(s):  
Qin Zhang ◽  
Shuxiang Zhang

Ovarian cancer is one of the leading causes of death among gynecological malignancies. Increasing evidence indicate that dysregulation of microRNAs (miRNAs) plays an important role in tumor radioresistance. The aim of the present study is to investigate whether microRNA-214 (miR-214) was involved in radioresistance of human ovarian cancer. Here, we showed that miR-214 was significantly up-regulated in ovarian cancer tissues and radioresistance ovarian cancer cell lines. Transfection of miR-214 agomir in radiosensitive ovarian cancer cell lines promoted them for resistance to ionizing radiation, whereas transfection of miR-214 antagomir in radioresistance ovarian cancer cell lines sensitized them to ionizing radiation again. Furthermore, we found miR-214 effectively promoted tumor radioresistance in xenograft animal experiment. Western blotting and quantitative real-time PCR demonstrated that miR-214 negatively regulated PTEN in radioresistance ovarian cancer cell lines and ovarian cancer tissues. Taken together, our data conclude that miR-214 contributes to radioresistance of ovarian cancer by directly targeting PTEN.


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