MicroRNA-29a plays a prominent role in PRIMA-1Met-induced apoptosis in ovarian cancer cells

The structural analog of the small 2,2-bis(hydroxymethyl)-1-azabicyclo[2,2,2]octan-3-one molecule named PRIMA-1Metfor ?p53 reactivation and induction of massive apoptosis? has been shown to inhibit cell growth and induce apoptosis in human tumor cells by restoring the tumor suppressor function of tumor protein p53. In several microRNA (miRNA) profiling studies related to ovarian cancer, different miRNAs associated with PRIMA-1Met have been reported, but miRNAs related to PRIMA-1Met-induced apoptosis remain unclear. This study was designed to explain the potential mechanism of PRIMA-1-induced apoptosis. According to the MTSassay and fluorescence-activated cell sorting (FACS) analysis results, PRIMA-1Met induced a significant decrease in cell viability and an increase in apoptosis in both A2780 and Caov-3 cells, regardless of p53 status. PRIMA-1Met upregulated miRNA-29a in both cell lines. To determine the effect of miRNA-29a on PRIMA-1Met-induced apoptosis, A2780 and Caov-3 cells were transfected with miRNA-29a inhibitor. After treatment with PRIMA-1Met, cell viability increased and apoptosis decreased in the transfected cells. The results of this study suggest that miRNA-29a potentially regulates PRIMA-1Met-induced apoptosis in ovarian cancer cells.

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ZEB1 Promotes Chemoresistance to Cisplatin in Ovarian Cancer Cells by Suppressing SLC3A2

Chemotherapy ◽

10.1159/000493864 ◽

2018 ◽

Vol 63 (5) ◽

pp. 262-271 ◽

Cited By ~ 10

Author(s):

Yajie Cui ◽

Li Qin ◽

Defu Tian ◽

Ting Wang ◽

Lijing Fan ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Viability ◽

Cancer Cells ◽

Tumor Development ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Cell Surface Molecule ◽

Important Regulator ◽

Induced Apoptosis

Ovarian cancer is one of the deadliest gynecological malignancies in women. Chemoresistance has been a major obstacle for ovarian cancer treatment. Zinc finger E-box-binding homeobox 1 (ZEB1) is an important regulator of tumor development in various types of cancer. Abnormal expression of SLC3A2 (CD98hc), a type 2 transmembrane cell surface molecule, has been described in several cancers. This study was designed to investigate the role of ZEB1 and SLC3A2 in the chemoresistance to cisplatin in ovarian cancer cells. We found that ZEB1 was increased in cisplatin-resistant SKOV3/DPP cells. Downregulation of ZEB1 significantly decreased cell viability in response to cisplatin, increased cisplatin-induced apoptosis, and decreased migration and invasion in the presence of cisplatin. In addition, downregulation of ZEB1 decreased the volume and weight of implanted tumors. SLC3A2 was decreased in cisplatin-resistant SKOV3/DPP cells. Upregulation of SLC3A2 significantly decreased cell viability in response to cisplatin, increased cisplatin-induced apoptosis, and decreased migration and invasion in the presence of cisplatin. Moreover, upregulation of SLC3A2 decreased the volume and weight of implanted tumors. Downregulation of ZEB1 resulted in a significant increase of SLC3A2 expression. Moreover, downregulation of SLC3A2 significantly inhibited ZEB1 knockdown-mediated inhibition of cisplatin-resistance. ZEB1-mediated regulation of SLC3A2 was involved in the chemoresistance to cisplatin in ovarian cancer cells. Overall, we provide new insights into the mechanism of chemoresistance to cisplatin in ovarian cancer cells. ZEB1/SLC3A2 may be promising therapeutic targets for enhancement of the sensitivity of ovarian cancer cells to cisplatin-mediated chemotherapy.

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Lupeol Inhibits Proliferation and Promotes Apoptosis of Ovarian Cancer Cells by Inactivating Phosphoinositide-3-Kinase/Protein Kinase B/ Mammalian Target of Rapamycin Pathway

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.19:206-210 ◽

2020 ◽

Vol 19 (2) ◽

pp. 206-210

Author(s):

Feng Chen ◽

Bei Zhang

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Protein Kinase ◽

Cell Viability ◽

Cancer Cells ◽

Protein Kinase B ◽

Mammalian Target Of Rapamycin ◽

Target Of Rapamycin ◽

Ovarian Cancer Cells ◽

Phosphoinositide 3 Kinase

Lupeol exhibits multiple pharmacological activities including, anticancerous, anti-inflammatory, and antioxidant. The aim of this study was to explore the anticancerous activity of lupeol on ovarian cancer cells and examine its mechanism of action. To this end, increasing concentrations of lupeol on cell viability, cell cycle, and apoptosis in Caov-3 cells were evaluated. Lupeol inhibited cell viability, induced G1 phase arrest in cell cycle, increased cell apoptosis, and inhibited the ratio of phospho-Akt/protein kinase B and phospho-mammalian target of rapamycin/mammalian target of rapamycin. In conclusion, these data suggest that lupeol may play a therapeutic role in ovarian cancer.

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Cooperative effect of adenoviral p53 gene therapy and standard chemotherapy in ovarian cancer cells independent of the endogenous p53 status

Cancer Gene Therapy ◽

10.1038/sj.cgt.7700727 ◽

2004 ◽

Vol 11 (8) ◽

pp. 547-554 ◽

Cited By ~ 16

Author(s):

Sven R Quist ◽

Shan Wang-Gohrke ◽

Tanja Köhler ◽

Rolf Kreienberg ◽

Ingo B Runnebaum

Keyword(s):

Ovarian Cancer ◽

Gene Therapy ◽

Cancer Cells ◽

P53 Gene ◽

Cooperative Effect ◽

Ovarian Cancer Cells ◽

Standard Chemotherapy ◽

P53 Status

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High expression of crystallin αB represents an independent molecular marker for unfavourable ovarian cancer patient outcome and impairs TRAIL- and cisplatin-induced apoptosis in human ovarian cancer cells

International Journal of Cancer ◽

10.1002/ijc.27975 ◽

2012 ◽

Vol 132 (12) ◽

pp. 2820-2832 ◽

Cited By ~ 21

Author(s):

Juliane Volkmann ◽

Ute Reuning ◽

Martina Rudelius ◽

Norman Häfner ◽

Tibor Schuster ◽

...

Keyword(s):

Patient Outcome ◽

Ovarian Cancer ◽

Molecular Marker ◽

Cancer Patient ◽

Cancer Cells ◽

Ovarian Cancer Patient ◽

High Expression ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Induced Apoptosis

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Galangin, a Flavonoid from Lesser Galangal, Induced Apoptosis via p53-Dependent Pathway in Ovarian Cancer Cells

Molecules ◽

10.3390/molecules25071579 ◽

2020 ◽

Vol 25 (7) ◽

pp. 1579 ◽

Cited By ~ 4

Author(s):

Haizhi Huang ◽

Allen Y. Chen ◽

Xingqian Ye ◽

Rongfa Guan ◽

Gary O. Rankin ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Regulatory Protein ◽

Ovarian Cancer Cells ◽

Apoptotic Pathway ◽

Bax Protein ◽

Platinum Based Chemotherapy ◽

Phosphorylated Akt ◽

Induced Apoptosis

Among women worldwide, ovarian cancer is one of the most dangerous cancers. Patients undergoing platinum-based chemotherapy might get adverse side effects and develop resistance to drugs. In recent years, natural compounds have aroused growing attention in cancer treatment. Galangin inhibited the growth of two cell lines, A2780/CP70 and OVCAR-3, more strongly than the growth of a normal ovarian cell line, IOSE 364. The IC50 values of galangin on proliferation of A2780/CP70, OVCAR-3 and IOSE 364 cells were 42.3, 34.5, and 131.3 μM, respectively. Flow cytometry analysis indicated that galangin preferentially induced apoptosis in both ovarian cancer cells with respect to normal ovarian cells. Galangin treatment increased the level of cleaved caspase-3 and -7 via the p53-dependent intrinsic apoptotic pathway by up-regulating Bax protein and via the p53-dependent extrinsic apoptotic pathway by up-regulating DR5 protein. By down-regulating the level of p53 with 20 μM pifithrin-α (PFT-α), the apoptotic rates of OVCAR-3 cells induced by galangin treatment (40 μM) were significantly decreased from 18.2% to 10.2%, indicating that p53 is a key regulatory protein in galangin-induced apoptosis in ovarian cancer cells. Although galangin up-regulated the expression of p21, it had little effect on the cell cycle of the two ovarian cancer cell lines. Furthermore, the levels of phosphorylated Akt and phosphorylated p70S6K were decreased through galangin treatment, suggesting that the Akt/p70S6K pathways might be involved in the apoptosis. Our results suggested that galangin is selective against cancer cells and can be used for the treatment of platinum-resistant ovarian cancers in humans.

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Isoflavones Isolated from the Seeds of Millettia ferruginea Induced Apoptotic Cell Death in Human Ovarian Cancer Cells

Molecules ◽

10.3390/molecules25010207 ◽

2020 ◽

Vol 25 (1) ◽

pp. 207 ◽

Cited By ~ 2

Author(s):

Yi-Yue Wang ◽

Jun Hyeok Kwak ◽

Kyung-Tae Lee ◽

Tsegaye Deyou ◽

Young Pyo Jang ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Death ◽

Cancer Cells ◽

Caspase 3 ◽

Apoptotic Cell ◽

Apoptotic Cell Death ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Millettia Ferruginea ◽

Induced Apoptosis

The seeds of Millettia ferruginea are used in fishing, pesticides, and folk medicine in Ethiopia. Here, the anti-cancer effects of isoflavones isolated from M. ferruginea were evaluated in human ovarian cancer cells. We found that isoflavone ferrugone and 6,7-dimethoxy-3’,4’-methylenedioxy-8-(3,3-dimethylallyl)isoflavone (DMI) had potent cytotoxic effects on human ovarian cancer cell A2780 and SKOV3. Ferrugone and DMI treatment increased the sub-G1 cell population in a dose-dependent manner in A2780 cells. The cytotoxic activity of ferrugone and DMI was associated with the induction of apoptosis, as shown by an increase in annexin V-positive cells. Z-VAD-fmk, a broad-spectrum caspase inhibitor, and z-DEVD-fmk, a caspase-3 inhibitor, significantly reversed both the ferrugone and DMI-induced apoptosis, suggesting that cell death stimulated by the isoflavones is mediated by caspase-3-dependent apoptosis. Additionally, ferrugone-induced apoptosis was found to be caspase-8-dependent, while DMI-induced apoptosis was caspase-9-dependent. Notably, DMI, but not ferrugone, increased the intracellular levels of reactive oxygen species (ROS), and antioxidant N-acetyl-L-cysteine (NAC) attenuated the pro-apoptotic activity of DMI. These data suggest that DMI induced apoptotic cell death through the intrinsic pathway via ROS production, while ferrugone stimulated the extrinsic pathway in human ovarian cancer cells.

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Demethoxycurcumin inhibited human epithelia ovarian cancer cells’ growth via up-regulating miR-551a

Tumor Biology ◽

10.1177/1010428317694302 ◽

2017 ◽

Vol 39 (3) ◽

pp. 101042831769430 ◽

Cited By ~ 10

Author(s):

Zhenhua Du ◽

Xianqun Sha

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Ovarian Cancer Cells ◽

Natural Form ◽

Ovarian Cancer Cell Lines ◽

Induced Apoptosis ◽

Tumor Suppressive Function ◽

Cancer Tissues

Curcumin is a natural agent that has ability to dampen tumor cells’ growth. However, the natural form of curcumin is prone to degrade and unstable in vitro. Here, we demonstrated that demethoxycurcumin (a curcumin-related demethoxy compound) could inhibit cell proliferation and induce apoptosis of ovarian cancer cells. Moreover, IRS2/PI3K/Akt axis was inactivated in cells treated with demethoxycurcumin. Quantitative real-time reverse transcription polymerase chain reaction demonstrated that miR-551a was down-regulated in ovarian cancer tissues and ovarian cancer cell lines. Over-expression of miR-551a inhibited cell proliferation and induced apoptosis of ovarian cancer cells, whereas down-regulation of miR-551a exerted the opposite function. Luciferase assays confirmed that there was a binding site of miR-551a in IRS2, and we found that miR-551a exerted tumor-suppressive function by targeting IRS2 in ovarian cancer cells. Remarkably, miR-551a was up-regulated in the cells treated with demethoxycurcumin, and demethoxycurcumin suppressed IRS2 by restoration of miR-551a. In conclusion, demethoxycurcumin hindered ovarian cancer cells’ malignant progress via up-regulating miR-551a.

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