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

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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191 RISK ASSESSMENT OF BISPHENOL A, AN ENDOCRINE DISRUPTOR, VIA PROLIFERATIVE EFFECT ON THE GROWTH OF ESTROGEN-DEPENDENT OVARIAN CANCER IN CELLULAR AND ANIMAL MODELS

Reproduction Fertility and Development ◽

10.1071/rdv25n1ab191 ◽

2013 ◽

Vol 25 (1) ◽

pp. 244

Author(s):

K.-A. Hwang ◽

K.-C. Choi

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cell Proliferation ◽

Bisphenol A ◽

Cancer Cells ◽

The Body ◽

Brdu Incorporation ◽

Ovarian Cancer Cells ◽

Tumour Proliferation

One of estrogens in the body, 17β-oestradiol (E2), is a pleiotropic hormone that regulates the growth and differentiation of many tissues and also acts as a mitogen that promotes the development and proliferation of hormone-responsive cancers such as breast and ovarian carcinomas. Xenoestrogens are chemical compounds that imitate oestrogen in living organisms and are classified as a type of endocrine-disrupting chemical (EDC). Bisphenol A (BPA) is a widely used industrial compound, and also known as an EDC and especially a xenoestrogen. In this study, we examined the effect of E2 or BPA on the cell growth of BG-1 ovarian cancer cells in vivo and in vitro. In the cell proliferation assay in vitro, E2 or BPA increased the growth of the BG-1 ovarian cancer cells expressing oestrogen receptors (ER). Their proliferation activity was reversed by the treatment of ICI 182 780, a well-known antagonist of ER, which demonstrates that the cell proliferation by E2 or BPA is mediated by ER and BPA certainly acts as a xenoestrogen in the BG-1 ovarian cancer cells. Clearly, E2 and BPA increased the expression of cyclin D1, a factor responsible for the G1/S cell cycle transition. These reagents also decreased the expression of p21, a potent cyclin-dependent kinase (CDK) inhibitor that arrests the cell cycle in the G1 phase. As a result, they promoted the proliferation of BG-1 cells via upregulation of the cell cycle progression. In mice xenograft models transplanted with BG-1 ovarian cancer cells, E2 or BPA administration significantly induced the tumour proliferation compared with vehicle (corn oil) treatment for 10 weeks, which was identified by the measurement of tumour volume and histological analysis on tumour tissues such as hematoxylin and eosin (H&E) staining and BrdU incorporation assay. Taken together, as an EDC having a xenoestrogenic activity, BPA was demonstrated to have a risk of tumour proliferation in oestrogen-dependent cancers such as ovarian cancer. This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Education, Science and Technology (MEST) of government of Korea (no. 2011-0015385).

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Follicle-Stimulating Hormone Is an Autocrine Regulator of the Ovarian Cancer Metastatic Niche Through Notch Signaling

Journal of the Endocrine Society ◽

10.1210/js.2018-00272 ◽

2018 ◽

Vol 3 (2) ◽

pp. 340-357 ◽

Cited By ~ 3

Author(s):

Sakshi Gera ◽

Sandeep Kumar S. ◽

Shalini N Swamy ◽

Rahul Bhagat ◽

Annapurna Vadaparty ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Notch Signaling ◽

Cancer Cells ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Ovarian Cancer Cells ◽

Fsh Receptor ◽

Ovarian Cancer Cell Lines ◽

Tumor Tissues

Abstract The association between the upregulated Notch and FSH signaling and ovarian cancer is well documented. However, their signaling has been investigated independently and only in the primary tumor tissues. The aim of this study was to investigate the interactive effects of FSH and Notch signaling on ovarian cancer proliferation, formation, and maintenance of disseminated ovarian cancer cells. The roles of Notch and FSH in ovarian cancer pathogenesis were investigated with ovarian cancer cell lines and specific antibodies against Notch and FSH receptor (FSHR). FSH upregulated Notch signaling and proliferation in ovarian cancer cells. High levels of FSH were detected in the ascites of patients with serous ovarian adenocarcinoma. Spheroids from the patients’ ascites, as well as the spheroids from ovarian cancer cell lines under low attachment culture conditions, expressed FSHβ subunit mRNA and secreted the hormone into the medium. In contrast, primary ovarian tumor tissues and cell line monolayers expressed very low levels of FSHβ. Ovarian cancer cell spheroids also exhibited higher expression of FSH receptor and Notch downstream genes than their monolayer counterparts. A combination of FSHR and Notch antagonistic antibodies significantly inhibited spheroid formation and cell proliferation in vitro. This study demonstrates that spheroids in ascites express and secrete FSH, which regulates cancer cell proliferation and spheroidogenesis through Notch signaling, suggesting that FSH is an autocrine regulator of cancer metastasis. Furthermore, Notch and FSHR are potential immunotherapeutic targets for ovarian cancer treatment.

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Upregulation of forkhead box O3 transcription is involved in C2-ceramide induced apoptosis and autophagy in ovarian cancer cells in vitro

Molecular Medicine Reports ◽

10.3892/mmr.2014.2664 ◽

2014 ◽

Vol 10 (6) ◽

pp. 3099-3105 ◽

Cited By ~ 9

Author(s):

ZHISHAN JIN ◽

LANG ZHENG ◽

XIAOYAN XIN ◽

YUANYUE LI ◽

TENG HUA ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Ovarian Cancer Cells ◽

Forkhead Box ◽

Induced Apoptosis

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Knockdown of BRCA2 enhances cisplatin and cisplatin-induced autophagy in ovarian cancer cells

Endocrine Related Cancer ◽

10.1530/erc-17-0261 ◽

2018 ◽

Vol 25 (1) ◽

pp. 69-82 ◽

Cited By ~ 16

Author(s):

Biao Wan ◽

Leheyi Dai ◽

Li Wang ◽

Ying Zhang ◽

Hong Huang ◽

...

Keyword(s):

Ovarian Cancer ◽

Median Time ◽

Progression Free Survival ◽

Ovarian Cancer Cells ◽

Intact Cells ◽

Ovarian Cancer Cell Lines ◽

Tumor Tissues ◽

Cancer Tissues

Clinical implications of the BRCA2 expression level on treatments of ovarian cancer are controversial. Here, we demonstrated that platinum-resistant cancer had a higher percentage of high BRCA2 level (87.5% vs 43.6%, P = 0.001), and that patients with a low BRCA2 level in cancer tissues had longer progression-free survival (with a median time of 28.0 vs 12.0 months, P < 0.001) and platinum-free duration (with a median time of 19.0 vs 5.0 months, P < 0.001) compared with those with a high BRCA2 level. In human ovarian cancer cell lines CAOV-3 and ES-2, cisplatin induced an upregulation of the RAD51 protein, which was inhibited after silencing BRCA2; silencing BRCA2 enhanced the action of cisplatin in vitro and in vivo. Knockdown of BRCA2 promoted cisplatin-induced autophagy. Interestingly, the autophagy blocker chloroquine enhanced cisplatin in BRCA2-silenced cells accompanied by an increase in apoptotic cells, which did not occur in BRCA2-intact cells; chloroquine enhanced the efficacy of cisplatin against BRCA2-silenced CAOV-3 tumors in vivo, with an increase in LC3-II level in tumor tissues. Sensitization of cisplatin was also observed in BRCA2-silenced CAOV-3 cells after inhibiting ATG7, confirming that chloroquine modulated the sensitivity via the autophagy pathway. These data suggest that a low BRCA2 level can predict better platinum sensitivity and prognosis, and that the modulation of autophagy can be a chemosensitizer for certain cancers.

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Mesothelin enhances invasion of ovarian cancer by inducing MMP-7 through MAPK/ERK and JNK pathways

Biochemical Journal ◽

10.1042/bj20110282 ◽

2012 ◽

Vol 442 (2) ◽

pp. 293-302 ◽

Cited By ~ 69

Author(s):

Ming-Cheng Chang ◽

Chi-An Chen ◽

Pao-Jen Chen ◽

Ying-Cheng Chiang ◽

Yu-Li Chen ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Tumour Progression ◽

Cancer Invasion ◽

Mitogen Activated Protein Kinase ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Cancer Tissues ◽

Specific Inhibitors

Ovarian cancer has one of the highest mortalities in malignancies in women, but little is known of its tumour progression properties and there is still no effective molecule that can monitor its growth or therapeutic responses. MSLN (mesothelin), a secreted protein that is overexpressed in ovarian cancer tissues with a poor clinical outcome, has been previously identified to activate PI3K (phosphoinositide 3-kinase)/Akt signalling and inhibit paclitaxel-induced apoptosis. The present study investigates the correlation between MSLN and MMP (matrix metalloproteinase)-7 in the progression of ovarian cancer, and the mechanism of MSLN in enhancing ovarian cancer invasion. The expression of MSLN correlated well with MMP-7 expression in human ovarian cancer tissues. Overexpressing MSLN or ovarian cancer cells treated with MSLN showed enhanced migration and invasion of cancer cells through the induction of MMP-7. MSLN regulated the expression of MMP-7 through the ERK (extracellular-signal-regulated kinase) 1/2, Akt and JNK (c-Jun N-terminal kinase) pathways. The expression of MMP-7 and the migrating ability of MSLN-treated ovarian cancer cells were suppressed by ERK1/2- or JNK-specific inhibitors, or a decoy AP-1 (activator protein 1) oligonucleotide in in vitro experiments, whereas in vivo animal experiments also demonstrated that mice treated with MAPK (mitogen-activated protein kinase)/ERK- or JNK-specific inhibitors could decrease intratumour MMP-7 expression, delay tumour growth and extend the survival of the mice. In conclusion, MSLN enhances ovarian cancer invasion by MMP-7 expression through the MAPK/ERK and JNK signal transduction pathways. Blocking the MSLN-related pathway could be a potential strategy for inhibiting the growth of ovarian cancer.

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circRNA-UBAP2 promotes the proliferation and inhibits apoptosis of ovarian cancer though miR-382-5p/PRPF8 axis

10.21203/rs.2.23146/v1 ◽

2020 ◽

Author(s):

Qin Xu ◽

Bo Deng ◽

Manlin Li ◽

Yang Chen ◽

Li Zhuan

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Target Gene ◽

Circular Rnas ◽

Ovarian Cancer Cells ◽

Competing Endogenous Rnas ◽

Cancer Tissues

Abstract Objective: circular RNAs (circRNAs) have been reported to be essential regulators of multiple malignant cancers. However, the functions of circRNAs in ovarian cancer need to be further explored. The aim of our study is to explore the role of circRNA-UBAP2 in ovarian cancer and its mechanism. Results: circRNA-UBAP2 was upregulated in ovarian cancer tissues and cell lines. Knockdown of circRNA-UBAP2 inhibited cell proliferation and promoted cell apoptosis, but circRNA-UBAP2 overexpressed got opposite results. In addition, circRNA-UBAP2 targeted miR-382-5p and downregulated its expression, PRPF8 was a target gene of miR-382-5p. Furthemore, circRNA-UBAP2/miR-382-5p/PRPF8 axis affected the proliferation, apoptosis and cell cycle of ovarian cancer through the mechanism of competing endogenous RNAs (ceRNA). Conclusion: circRNA-UBAP2 acted as a ceRNA to sponged miR-382-5p, increased the expression level of PRPF8, and prompted proliferation and inhibited apoptosis in ovarian cancer cells.

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circRNA-UBAP2 promotes the proliferation and inhibits apoptosis of ovarian cancer though miR-382-5p/PRPF8 axis

10.21203/rs.2.23146/v2 ◽

2020 ◽

Author(s):

Qin Xu ◽

Bo Deng ◽

Manlin Li ◽

Yang Chen ◽

Li Zhuan

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Target Gene ◽

Circular Rnas ◽

Ovarian Cancer Cells ◽

Competing Endogenous Rnas ◽

Cancer Tissues

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An Effective Inhibitory Strategy of Low Steady Magnetic Field on Ovarian Cancer

10.21203/rs.3.rs-208755/v1 ◽

2021 ◽

Author(s):

Xiaodi Li ◽

Yanwen Fang ◽

Zhicai Fang ◽

Ping Wang ◽

Jun Zhu

Keyword(s):

Magnetic Field ◽

Ovarian Cancer ◽

Cancer Cells ◽

Cell Model ◽

Inhibitory Effect ◽

Ovarian Cancer Cells ◽

Magnetic Intensity ◽

Ovarian Cancer Cell Lines

Abstract To estimate the effect of a steady-state magnetic field (SMF) with low magnetic intensity gradient on the apoptosis-promoting factors related to cancer cells, we systematically select SMF with 0.2T, 0.4T and 0.6T to study their effect on different ovarian cancer lines. An in vitro cell model system about two kinds of ovarian cancer lines is established, whose viability and intracellular factors are detected by CCK-8, confocal microscopy and flow cytometry method. The results demonstrate that the apoptosis rate of ovarian cancer cells is increased with the enhancement of SMF magnetic intensity. Furthermore, we detect an increasing ROS and intracellular Ca2+ levels in ovarian cancer cells, which can be caused by SMF. The results suggest that ROS and Ca2+ levels are the main reason for the significant apoptosis of ovarian cancer cell lines in SMF. Moreover, an in vivo experiment also reveals that SMF has a strong inhibitory effect on ovarian cancer. Therefore, the inhibitory strategy is an effective, which has a great potential in the treatment of drug-resistant ovarian cancer.

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LncRNA GAS5 suppresses ovarian cancer by inducing inflammasome formation

Bioscience Reports ◽

10.1042/bsr20171150 ◽

2018 ◽

Vol 38 (2) ◽

Cited By ~ 21

Author(s):

Jie Li ◽

Chen Yang ◽

Yinguang Li ◽

Aiyue Chen ◽

Li Li ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cell Apoptosis ◽

Colony Formation ◽

Sandwich Elisa ◽

Ovarian Cancer Cells ◽

Cancer Tissues ◽

Lncrna Gas5

Objective: Long noncoding RNA growth arrest-specific transcript 5 (lncRNA GAS5) is involved in various kinds of cancer. However, the role of lncGAS5 in the development of ovarian cancer remains unclear. In the present study, we explored the cellular mechanism and clinical value of lncRNA GAS5 in ovarian cancer. Methods: Quantitative real-time PCR was used to detect mRNA level of lncRNA GAS5 in 20 ovarian cancer tissues. The effect of lncRNA GAS5 on cell proliferation was performed using CCK-8 assay. Cell apoptosis was evaluated by flow cytometry. Western blotting was used to detect the protein level of lncRNA GAS5 potential target. Standard sandwich ELISA was used to quantify the level of inflammatory cytokines. The cells with stable expression of lncRNA GAS5 were injected into nude mice to study the effect of lncRNA GAS5 on tumorigenesis in vivo. Results: The expression of lncRNA GAS5 was significantly decreased in ovarian cancer tissues. Decrease in lncRNA GAS5 expression resulted in increased cell proliferation and colony formation and reduced ovarian cancer cell apoptosis. In contrast, exogenous overexpression of lncRNA GAS5 in ovarian cancer cells inhibited proliferation, colony formation, and apoptosis in ovarian cancer cells. In addition, the role of lncRNA GAS5 in ovarian cancer was associated with inflammasome formation and pyroptosis. Conclusion: These results suggested that lncRNA GAS5 acts as tumor suppressor and could be used as a potential treatment target for diagnosis and therapy of ovarian cancer.

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Targeting Ovarian Cancer Cells Overexpressing CD44 with Immunoliposomes Encapsulating Glycosylated Paclitaxel

International Journal of Molecular Sciences ◽

10.3390/ijms20051042 ◽

2019 ◽

Vol 20 (5) ◽

pp. 1042 ◽

Cited By ~ 5

Author(s):

Apriliana Cahya Khayrani ◽

Hafizah Mahmud ◽

Aung Ko Ko Oo ◽

Maram H. Zahra ◽

Miharu Oze ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Stem Cell Marker ◽

Ovarian Cancer Cells ◽

Cancer Therapies ◽

Ovarian Cancer Cell Lines ◽

Tumor Selective

Paclitaxel (PTX) is one of the front-line drugs approved for the treatment of ovarian cancer. However, the application of PTX is limited due to the significant hydrophobicity and poor pharmacokinetics. We previously reported target-directed liposomes carrying tumor-selective conjugated antibody and encapsulated glycosylated PTX (gPTX-L) which successfully overcome the PTX limitation. The tubulin stabilizing activity of gPTX was equivalent to that of PTX while the cytotoxic activity of gPTX was reduced. In human ovarian cancer cell lines, SK-OV-3 and OVK18, the concentration at which cell growth was inhibited by 50% (IC50) for gPTX range from 15–20 nM, which was sensitive enough to address gPTX-L with tumor-selective antibody coupling for ovarian cancer therapy. The cell membrane receptor CD44 is associated with cancer progression and has been recognized as a cancer stem cell marker including ovarian cancer, becoming a suitable candidate to be targeted by gPTX-L therapy. In this study, gPTX-loading liposomes conjugated with anti-CD44 antibody (gPTX-IL) were assessed for the efficacy of targeting CD44-positive ovarian cancer cells. We successfully encapsulated gPTX into liposomes with the loading efficiency (LE) more than 80% in both of gPTX-L and gPTX-IL with a diameter of approximately 100 nm with efficacy of enhanced cytotoxicity in vitro and of convenient treatment in vivo. As the result, gPTX-IL efficiently suppressed tumor growth in vivo. Therefore gPTX-IL could be a promising formulation for effective ovarian cancer therapies.

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