Abstract 4028: Molecular mechanisms of magnolin resistance in ovarian cancer cells

Ovarian cancer is the gynecological malignancy with the poorest prognosis, in part due to its high incidence of recurrence. Platinum agents are widely used as a first-line treatment against ovarian cancer. Recurrent tumors, however, frequently demonstrate acquired chemo-resistance to platinum agent toxicity. To improve chemo-sensitivity, combination chemotherapy regimens have been investigated. This study examined anti-tumor effects and molecular mechanisms of cytotoxicity of Oldenlandia diffusa (OD) extracts on ovarian cancer cells, in particular, cells resistant to cisplatin. Six ovarian cancer cells including A2780 and cisplatin-resistant A2780 (A2780cis) as representative cell models were used. OD was extracted with water (WOD) or 50% methanol (MOD). MOD significantly induced cell death in both cisplatin-sensitive cells and cisplatin-resistant cells. The combination treatment of MOD with cisplatin reduced viability in A2780cis cells more effectively than treatment with cisplatin alone. MOD in A2780cis cells resulted in downregulation of the epigenetic modulator KDM1B and the DNA repair gene DCLRE1B. Transcriptional suppression of KDM1B and DCLRE1B induced cisplatin sensitivity. Knockdown of KDM1B led to downregulation of DCLRE1B expression, suggesting that DCLRE1B was a KDM1B downstream target. Taken together, OD extract effectively promoted cell death in cisplatin-resistant ovarian cancer cells under cisplatin treatment through modulating KDM1B and DCLRE1B.

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Anticancer effects of novel resveratrol analogues on human ovarian cancer cells

Molecular BioSystems ◽

10.1039/c7mb00128b ◽

2017 ◽

Vol 13 (6) ◽

pp. 1131-1141 ◽

Cited By ~ 9

Author(s):

Daniele Vergara ◽

Stefania De Domenico ◽

Andrea Tinelli ◽

Eleonora Stanca ◽

Loretta L. Del Mercato ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Anticancer Effects ◽

Anti Cancer ◽

Resveratrol Analogues

We describe the molecular mechanisms of the action of novel trans-restricted analogues of resveratrol with enhanced anti-cancer properties.

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Matrine inhibits the development and progression of ovarian cancer by repressing cancer associated phosphorylation signaling pathways

Cell Death and Disease ◽

10.1038/s41419-019-2013-3 ◽

2019 ◽

Vol 10 (10) ◽

Cited By ~ 3

Author(s):

Xi Zhang ◽

Guoqing Hou ◽

Andong Liu ◽

Hui Xu ◽

Yang Guan ◽

...

Keyword(s):

Ovarian Cancer ◽

Side Effects ◽

Cancer Cells ◽

Signaling Pathways ◽

Molecular Mechanisms ◽

Chemotherapy Resistance ◽

Treatment Strategies ◽

Ovarian Cancer Cells

Abstract Ovarian cancer remains the most lethal gynecologic malignancy with late detection and acquired chemoresistance. Advanced understanding of the pathophysiology and novel treatment strategies are urgently required. A growing body of proteomic investigations suggest that phosphorylation has a pivotal role in the regulation of ovarian cancer associated signaling pathways. Matrine has been extensively studied for its potent anti-tumor activities. However, its effect on ovarian cancer cells and underlying molecular mechanisms remain unclear. Herein we showed that matrine treatment inhibited the development and progression of ovarian cancer cells by regulating proliferation, apoptosis, autophagy, invasion and angiogenesis. Matrine treatment retarded the cancer associated signaling transduction by decreasing the phosphorylation levels of ERK1/2, MEK1/2, PI3K, Akt, mTOR, FAK, RhoA, VEGFR2, and Tie2 in vitro and in vivo. Moreover, matrine showed excellent antitumor effect on chemoresistant ovarian cancer cells. No obvious toxic side effects were observed in matrine-administrated mice. As the natural agent, matrine has the potential to be the targeting drug against ovarian cancer cells with the advantages of overcoming the chemotherapy resistance and decreasing the toxic side effects.

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WOMEN IN CANCER THEMATIC REVIEW: Ovarian cancer–peritoneal cell interactions promote extracellular matrix processing

Endocrine Related Cancer ◽

10.1530/erc-16-0320 ◽

2016 ◽

Vol 23 (11) ◽

pp. T155-T168 ◽

Cited By ~ 11

Author(s):

C Ricciardelli ◽

N A Lokman ◽

M P Ween ◽

M K Oehler

Keyword(s):

Ovarian Cancer ◽

Extracellular Matrix ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Cancer Metastasis ◽

Cell Interaction ◽

Peritoneal Cell ◽

Ovarian Cancer Cells ◽

Peritoneal Cells ◽

Proteomic Approach

Ovarian cancer has a distinct tendency for metastasising via shedding of cancerous cells into the peritoneal cavity and implanting onto the peritoneum that lines the pelvic organs. Once ovarian cancer cells adhere to the peritoneal cells, they migrate through the peritoneal layer and invade the local organs. Alterations in the extracellular environment are critical for tumour initiation, progression and intra-peritoneal dissemination. To increase our understanding of the molecular mechanisms involved in ovarian cancer metastasis and to identify novel therapeutic targets, we recently studied the interaction of ovarian cancer and peritoneal cells using a proteomic approach. We identified several extracellular matrix (ECM) proteins including, fibronectin, TGFBI, periostin, annexin A2 and PAI-1 that were processed as a result of the ovarian cancer–peritoneal cell interaction. This review focuses on the functional role of these proteins in ovarian cancer metastasis. Our findings together with published literature support the notion that ECM processing via the plasminogen–plasmin pathway promotes the colonisation and attachment of ovarian cancer cells to the peritoneum and actively contributes to the early steps of ovarian cancer metastasis.

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Molecular profile of breast versus ovarian cancer cells in response to treatment with the anticancer drugs cisplatin, carboplatin, doxorubicin, etoposide and taxol

Biological Chemistry ◽

10.1515/bc.2008.161 ◽

2008 ◽

Vol 389 (11) ◽

Cited By ~ 19

Author(s):

Hellinida Thomadaki ◽

Andreas Scorilas

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Anticancer Drugs ◽

Molecular Mechanisms ◽

Mrna Level ◽

Response To Treatment ◽

Molecular Profile ◽

Ovarian Cancer Cells ◽

Chemotherapy Response ◽

Cancer Type

Abstract We assessed changes in the apoptosis-related genes BCL2, BAX, BCL2L12, FAS and CASPASE-3 in OVCAR-3 human ovarian cancer cells and BT-20 human breast cancer cells to provide an insight into the molecular mechanisms involved in the response of these cells to treatment with anticancer drugs and to assess their value as potential biomarkers of chemotherapy response in breast and ovarian cancer. Cells were treated with different chemotherapeutic drugs (cisplatin, carboplatin, doxorubicin, etoposide and taxol) and assessed for changes in the expression of apoptosis-related genes at the mRNA level. Total RNA was extracted, reverse-transcribed into cDNA and amplified by PCR using gene-specific primers. GAPDH was used as a housekeeping gene. Cytotoxicity was assessed by MTT assay. Both cancer cell lines responded differentially at the molecular level to the drug treatments. OVCAR-3 cells showed more pronounced sensitivity and changes compared to BT-20 cells at the mRNA level for different apoptosis-related genes, leading to cell and cancer type dependence in conjunction with drug dependence.

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Overcoming chemotherapy resistance of ovarian cancer cells by liposomal cisplatin: Molecular mechanisms unveiled by gene expression profiling

Biochemical Pharmacology ◽

10.1016/j.bcp.2013.01.028 ◽

2013 ◽

Vol 85 (8) ◽

pp. 1077-1090 ◽

Cited By ~ 21

Author(s):

Martin Koch ◽

Michaela L. Krieger ◽

Daniel Stölting ◽

Norbert Brenner ◽

Manfred Beier ◽

...

Keyword(s):

Gene Expression ◽

Ovarian Cancer ◽

Gene Expression Profiling ◽

Cancer Cells ◽

Expression Profiling ◽

Molecular Mechanisms ◽

Chemotherapy Resistance ◽

Ovarian Cancer Cells

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Bromodomain-containing protein 4 regulates interleukin-34 expression in mouse ovarian cancer cells

Inflammation and Regeneration ◽

10.1186/s41232-020-00129-4 ◽

2020 ◽

Vol 40 (1) ◽

Author(s):

Nanumi Han ◽

Delnur Anwar ◽

Naoki Hama ◽

Takuto Kobayashi ◽

Hidefumi Suzuki ◽

...

Keyword(s):

Ovarian Cancer ◽

Tumor Growth ◽

Tumor Progression ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Ovarian Cancer Cell Line ◽

Cancer Cell Line ◽

Ovarian Cancer Cells ◽

Mouse Tumor

Abstract Background Interleukin (IL)-34 acts as an alternative ligand for the colony-stimulating factor-1 receptor and controls the biology of myeloid cells, including survival, proliferation, and differentiation. IL-34 has been reported to be expressed in cancer cells and to promote tumor progression and metastasis of certain cancers via the promotion of angiogenesis and immunosuppressive macrophage differentiation. We have shown in our previous reports that targeting IL-34 in chemo-resistant tumors in vitro resulted in a remarkable inhibition of tumor growth. Also, we reported poor prognosis in patients with IL-34-expressing tumor. Therefore, blocking of IL-34 is considered as a promising therapeutic strategy to suppress tumor progression. However, the molecular mechanisms that control IL-34 production are still largely unknown. Methods IL-34 producing ovarian cancer cell line HM-1 was treated by bromodomain and extra terminal inhibitor JQ1. The mRNA and protein expression of IL-34 was evaluated after JQ1 treatment. Chromatin immunoprecipitation was performed to confirm the involvement of bromodomain-containing protein 4 (Brd4) in the regulation of the Il34 gene. Anti-tumor effect of JQ1 was evaluated in mouse tumor model. Results We identified Brd4 as one of the critical molecules that regulate Il34 expression in cancer cells. Consistent with this, we found that JQ1 is capable of efficiently suppressing the recruitment of Brd4 to the promotor region of Il34 gene. Additionally, JQ1 treatment of mice bearing IL-34-producing tumor inhibited the tumor growth along with decreasing Il34 expression in the tumor. Conclusion The results unveiled for the first time the responsible molecule Brd4 that regulates Il34 expression in cancer cells and suggested its possibility as a treatment target.

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Eukaryotic initiation factor 3, subunit C silencing inhibits cell proliferation and promotes apoptosis in human ovarian cancer cells

Bioscience Reports ◽

10.1042/bsr20191124 ◽

2019 ◽

Vol 39 (8) ◽

Cited By ~ 3

Author(s):

Fang Wen ◽

Zhang-Ying Wu ◽

Lei Nie ◽

Qi-Zhu Zhang ◽

Yuan-Kun Qin ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Molecular Mechanisms ◽

Protein Translation ◽

Initiation Factor ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Eukaryotic Initiation Factor ◽

Translational Initiation

Abstract Ovarian cancer remains the leading cause of death among all gynaecological cancers, illustrating the urgent need to understand the molecular mechanisms involved in this disease. Eukaryotic initiation factor 3c (EIF3c) plays an important role in protein translation and cancer cell growth and proliferation, but its role in human ovarian cancer is unclear. Our results showed that EIF3c silencing significantly up-regulated 217 and down-regulated 340 genes. Ingenuity Pathway Analysis (IPA) indicated that the top differentially expressed genes are involved in ‘Classical Pathways’, ‘Diseases and Functions’ and ‘Networks’, especially those involved in signalling and cellular growth and proliferation. In addition, eIF3c silencing inhibited cellular proliferation, enhanced apoptosis and regulated the expression of apoptosis-associated proteins. In conclusion, these results indicate that by dysregulating translational initiation, eIF3c plays an important role in the proliferation and survival of human ovarian cancer cells. These results should provide experimental directions for further in-depth studies on important human ovarian cancer cell pathways.

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RNA-Binding Motif Protein 11 (RBM11) Serves as a Prognostic Biomarker and Promotes Ovarian Cancer Progression

Disease Markers ◽

10.1155/2021/3037337 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Chunhong Fu ◽

Ming Yuan ◽

Jie Sun ◽

Gang Liu ◽

Xiaojuan Zhao ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Molecular Mechanisms ◽

Rna Binding ◽

Prognostic Biomarker ◽

Xenograft Model ◽

Advanced Ovarian Cancer ◽

Ovarian Cancer Cells ◽

Binding Motif

Ovarian cancer is one of the most lethal gynecologic malignancies for women. Due to the lack of efficient target therapy, the overall survival rate for patients with advanced ovarian cancer is still low. Illustrating the molecular mechanisms dictating ovarian cancer progression is critically important to develop novel therapeutic agents. Here, we found that RNA-binding motif protein 11 (RBM11) was highly elevated in ovarian cancer tissues compared with normal ovary, while RBM11 depletion in ovarian cancer cells resulted in impaired cell growth and invasion. Moreover, knockdown of RBM11 also retarded tumor growth in the A2780 ovarian cancer xenograft model. Mechanically, we found that RBM11 positively regulated Akt/mTOR signaling pathway activation in ovarian cancer cells. Thus, these results identify RBM11 is a novel oncogenic protein and prognostic biomarker for ovarian cancers.

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