Strong cytotoxic effect of the bradykinin antagonist BKM-570 in ovarian cancer cells - analysis of the molecular mechanisms of its antiproliferative action

Purpose: To assess the cytotoxic effect of 5, 7-dihalo-8-quinolinol complex (DHQ) on ovarian cancer cells, and the mechanism of action involved.Methods: DHQ-mediated changes in cell viability were determined using MTT assay, while apoptosis was analyzed with flow cytometry. The effect of DHQ on cell migration was determined using inverted microscopy, while its effect on invasiveness was assessed with Giemsa dyeing. FACS Caliburinstrumentation was employed for analyzing the effect of DHQ on the cell cycle. The protein expressions of Wip1 and P53 were assayed by western blotting.Results: DHQ induced cytotoxicity against A2780 and OVCAR 3 cells in the concentration range of 0.25 - 12 μM (p < 0.05). In A2780 and OVCAR 3 cells, treatment with 12 μMDHQ resulted in 69.34 and 65.46 % apoptosis, respectively. The migratory potential and invasiveness of A2780 and OVCAR3 cells were significantly decreased by 12 μMDHQ, relative to untreated cells (p < 0.05). Moreover, treatment with 12 μMDHQ arrested cell cycle at G1/G0 phase in A2780 and OVCAR3 cells, but downregulated the protein expressions of Wip1 expression in A2780 and OVCAR3 cells.Conclusion: DHQ exerts cytotoxic effect on ovarian cancer cell growth via arrest of cell cycle and activation of apoptosis. Moreover, DHQ inhibits the migratory and invasive abilities of the cells. Thus, DHQ is a potential drug candidate for the management of ovarian cancer. Keywords: 5,7-Dihalo-8-quinolinol complex, Ovarian cancer, Cytotoxicity, Apoptosis, Invasiveness, Migration, Cell cycle

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CURCUMIN INDUCED CHANGES IN TP53 AND CYCLIN D1 ENHANCE CYTOTOXIC EFFECT OF CISPLATIN IN HUMAN OVARIAN CANCER CELLS

Biology of Reproduction ◽

10.1093/biolreprod/77.s1.157c ◽

2007 ◽

Vol 77 (Suppl_1) ◽

pp. 157-158

Author(s):

Kathleen Austin ◽

Edward Van Kirk ◽

N. Sreejayan ◽

William Murdoch ◽

Brenda Alexander

Keyword(s):

Ovarian Cancer ◽

Cyclin D1 ◽

Cancer Cells ◽

Cytotoxic Effect ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Induced Changes

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Promotion of Cell Death in Cisplatin-Resistant Ovarian Cancer Cells through KDM1B-DCLRE1B Modulation

International Journal of Molecular Sciences ◽

10.3390/ijms20102443 ◽

2019 ◽

Vol 20 (10) ◽

pp. 2443 ◽

Cited By ~ 2

Author(s):

Yeon Kyu Lee ◽

Jinyeong Lim ◽

So Young Yoon ◽

Jong Cheon Joo ◽

Soo Jung Park ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Death ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Ovarian Cancer Cells ◽

Repair Gene ◽

Gynecological Malignancy ◽

Downstream Target ◽

Dna Repair Gene ◽

Cisplatin Sensitivity

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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The Cytotoxic Effect of Combined Hyperthermia and Taxane Chemotherapy on Ovarian Cancer Cells: Results of an in vitro Study

European Surgical Research ◽

10.1159/000333393 ◽

2012 ◽

Vol 48 (2) ◽

pp. 55-63 ◽

Cited By ~ 7

Author(s):

M. Muller ◽

M. Chérel ◽

P.-F. Dupré ◽

S. Gouard ◽

M. Collet ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cytotoxic Effect ◽

In Vitro Study ◽

Vitro Study ◽

Ovarian Cancer Cells ◽

Taxane Chemotherapy

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

10.1158/1538-7445.am2018-4028 ◽

2018 ◽

Author(s):

Sun-Mi Yoo ◽

Cheol-Jung Lee ◽

Seung-Min Kim ◽

Seon-Yeon Cho ◽

Juhee Park ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Ovarian Cancer Cells

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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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