Sab concentrations indicate chemotherapeutic susceptibility in ovarian cancer cell lines

2018 ◽  
Vol 475 (21) ◽  
pp. 3471-3492 ◽  
Author(s):  
Iru Paudel ◽  
Sean M. Hernandez ◽  
Gilda M. Portalatin ◽  
Tara P. Chambers ◽  
Jeremy W. Chambers
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Ovarian Cancer Cell ◽  
Prognostic Biomarker ◽  
Chemotherapeutic Agents ◽  
Mitochondrial Outer Membrane ◽  
Expression Data ◽  
Apoptotic Pathway ◽  
Gynecological Malignancy ◽  
Ovarian Cancer Cell Lines

The occurrence of chemotherapy-resistant tumors makes ovarian cancer (OC) the most lethal gynecological malignancy. While many factors may contribute to chemoresistance, the mechanisms responsible for regulating tumor vulnerability are under investigation. Our analysis of gene expression data revealed that Sab, a mitochondrial outer membrane (MOM) scaffold protein, was down-regulated in OC patients. Sab-mediated signaling induces cell death, suggesting that this apoptotic pathway is diminished in OC. We examined Sab expression in a panel of OC cell lines and found that the magnitude of Sab expression correlated to chemo-responsiveness; wherein, OC cells with low Sab levels were chemoresistant. The Sab levels were reflected by a corresponding amount of stress-induced c-Jun N-terminal kinase (JNK) on the MOM. BH3 profiling and examination of Bcl-2 and BH3-only protein concentrations revealed that cells with high Sab concentrations were primed for apoptosis, as determined by the decrease in pro-survival Bcl-2 proteins and an increase in pro-apoptotic BH3-only proteins on mitochondria. Furthermore, overexpression of Sab in chemoresistant cells enhanced apoptotic priming and restored cellular vulnerability to a combination treatment of cisplatin and paclitaxel. Contrariwise, inhibiting Sab-mediated signaling or silencing Sab expression in a chemosensitive cell line resulted in decreased apoptotic priming and increased resistance. The effects of silencing on Sab on the resistance to chemotherapeutic agents were emulated by the silencing or inhibition of JNK, which could be attributed to changes in Bcl-2 protein concentrations induced by sub-chronic JNK inhibition. We propose that Sab may be a prognostic biomarker to discern personalized treatments for OC patients.

scholarly journals Hepsin shows inhibitory effects through apoptotic pathway on ovarian cancer cell lines

2006 ◽  
Author(s):  
Keiichiro Nakamura ◽  
Yasutomo Nasu ◽  
Atsushi Hongo ◽  
Tamaki Matsuo ◽  
Junichi Kodama ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Inhibitory Effects ◽  
Apoptotic Pathway ◽  
Ovarian Cancer Cell Lines

Gedunin, a Novel Natural Substance, Inhibits Ovarian Cancer Cell Proliferation

2009 ◽  
Vol 19 (9) ◽  
pp. 1564-1569 ◽  
Author(s):  
Siddharth G. Kamath ◽  
Ning Chen ◽  
Yin Xiong ◽  
Robert Wenham ◽  
Sachin Apte ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Ovarian Cancer Cells ◽  
Expression Data ◽  
Ovarian Cancer Cell Lines

The discovery of more active therapeutic compounds is essential if the outcome for patients with advanced-stage epithelial ovarian cancer is to be improved. Gedunin, an extract of the neem tree, has been used as a natural remedy for centuries in Asia. Recently, gedunin has been shown to have potential in vitro antineoplastic properties; however, its effect on ovarian cancer cells is unknown. We evaluated the in vitro effect of gedunin on SKOV3, OVCAR4, and OVCAR8 ovarian cancer cell lines proliferation, alone and in the presence of cisplatin. Furthermore, we analyzed in vitro gedunin sensitivity data, integrated with genome-wide expression data from 54 cancer cell lines in an effort to identify genes and molecular pathways that underlie the mechanism of gedunin action. In vitro treatment of ovarian cancer cell lines with gedunin alone produced up to an 80% decrease in cell proliferation (P < 0.01) and, combining gedunin with cisplatin, demonstrated up to a 47% (P < 0.01) decrease in cell proliferation compared with cisplatin treatment alone. Bioinformatic analysis of integrated gedunin sensitivity and gene expression data identified 52 genes to be associated with gedunin sensitivity. These genes are involved in molecular functions related to cell cycle control, carcinogenesis, lipid metabolism, and molecular transportation. We conclude that gedunin has in vitro activity against ovarian cancer cells and, further, may enhance the antiproliferative effect of cisplatin. The molecular determinants of in vitro gedunin response are complex and may include modulation of cell survival and apoptosis pathways.

MicroRNAs that underlie response to salvage chemotherapy in ovarian cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10542-10542
Author(s):  
T. P. Boren ◽  
S. Cui ◽  
G. Chan ◽  
H. Dressman ◽  
J. M. Lancaster
Keyword(s):  
Ovarian Cancer ◽  
Regression Analysis ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Protein Translation ◽  
Cancer Cell Lines ◽  
Salvage Chemotherapy ◽  
Chemotherapeutic Agents ◽  
Ovarian Cancer Cell Lines

10542 Background: MicroRNAs (miRNAs) are non-protein coding, endogenous, small RNAs that can bind complementary mRNA to modulate gene expression and protein translation. Recent studies indicate that miRNAs may be mechanistically involved in ovarian cancer chemosensitivity and may play an important role in the development of chemoresistance. The objective of the current study was to explore the role of miRNAs in the response of platinum-resistant recurrent or persistent ovarian cancer to salvage chemotherapy. Methods: MicroRNA was extracted from 16 ovarian cancer cell lines. All samples were hybridized to a miRNA array that contained Ambion and Invitrogen probe sets. In parallel, the 16 ovarian cancer cell lines were treated with Doxorubicin, Topotecan, Paclitaxel, Docetaxel, and Gemcitabine, and their response to treatment evaluated using proliferation assays. Logistic regression analysis was used to identify miRNAs associated with responsiveness to individual chemotherapeutic agents. Results: Linear regression analysis identified a total of 39 miRNAs significantly associated with salvage chemotherapy responsiveness. Sixteen miRNAs were associated with response to Doxorubicin, 18 associated with response to Topotecan, 2 associated with response to Docetaxel, 9 associated with response to Paclitaxel, and 11 associated with response to Gemcitabine (p<0.05). Ten miRNAs were associated with more than one chemotherapy (miR-126, miR-199a, miR-202 [Doxorubicin, Topotecan, Gemcitabine], miR-26a, miR-320 [Doxorubicin, Topotecan], miR-181b [Doxorubicin, Topotecan, Paclitaxel], 181a [Topotecan, Gemcitabine, Adriamycin, Paclitaxel], miR-99b [Doxorubicin, Paclitaxel, Docetaxel], miR-31 [Docetaxel, Paclitaxel], miR-339 [Doxorubicin, Gemcitabine]). Conclusion: We have identified miRNAs that may influence ovarian cancer responsiveness to salvage chemotherapy. Ten of the miRNAs were associated with chemosensitivity to more than one drug. These miRNAs may regulate common determinants of chemoresistance and may also serve as novel therapeutic targets for patients with chemoresistant ovarian cancer. Further studies are warranted to validate these results. No significant financial relationships to disclose.

scholarly journals Niosome-encapsulated balanocarpol: compound isolation, characterisation, and cytotoxicity evaluation against human breast and ovarian cancer cell lines

2020 ◽  
Vol 31 (19) ◽  
pp. 195101 ◽  
Author(s):  
Mohammad A Obeid ◽  
Siti Aisya S Gany ◽  
Alexander I Gray ◽  
Louise Young ◽  
John O Igoli ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Breast ◽  
Breast And Ovarian Cancer ◽  
Ovarian Cancer Cell Lines

scholarly journals Difference between genomic actions of estrogen versus raloxifene in human ovarian cancer cell lines

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

scholarly journals miR-214 promotes radioresistance in human ovarian cancer cells by targeting PETN

2017 ◽  
Vol 37 (4) ◽  
Author(s):  
Qin Zhang ◽  
Shuxiang Zhang
Keyword(s):  
Ovarian Cancer ◽  
Ionizing Radiation ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Ovarian Cancer Cell Lines ◽  
Cancer Tissues

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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