The Effect of 3′-Hydroxy-3,4,5,4′-Tetramethoxy -stilbene, the Metabolite of the Resveratrol Analogue DMU-212, on the Motility and Proliferation of Ovarian Cancer Cells

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Abstract

Targeting tumor cell motility and proliferation is an extremely important challenge in the prevention of metastasis and improving the effectiveness of cancer treatment. We recently published data revealing that DMU-214, the metabolite of firmly cytotoxic resveratrol analogue DMU-212, exerted significantly higher biological activity than the parent compound in ovarian cancer cells. The aim of the present study was to assess the molecular mechanism of the potential anti-migration and anti-proliferative effect of DMU-214 in ovarian cancer cell line SKOV-3. We showed that DMU-214 reduced the migratory capacity of SKOV-3 cells. The microarray analysis indicated ontology groups of genes involved in processes of negative regulation of cell motility and proliferation. Furthermore, we found DMU-214 triggered changes in expression of several migration- and proliferation-related genes (SMAD7, THBS1, IGFBP3, KLF4, Il6, ILA, SOX4, IL15, SRF, RGCC, GPR56) and proteins (GPR56, RGCC, SRF, SMAD7, THBS1), which have been shown to interact to each other to reduce cell proliferation and motility. Our study showed for the first time that DMU-214 displayed anti-migratory and anti-proliferative activity in SKOV-3 ovarian cancer cells. On the basis of whole transcriptome analysis of these cells, we provide new insight into the role of DMU-214 in inhibition of processes related to metastasis.

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Cellular and molecular processes in ovarian cancer metastasis. A Review in the Theme: Cell and Molecular Processes in Cancer Metastasis.

Tsz-Lun Yeung, Cecilia S. Leung, Kay-Pong Yip … (2015)

Ovarian cancer is the most lethal gynecological malignancy. It is usually diagnosed at a late stage, with a 5-yr survival rate of <30%. The majority of ovarian cancer cases are diagnosed after tumors have widely spread within the peritoneal cavity, limiting the effectiveness of debulking surgery and chemotherapy. Owing to a substantially lower survival rate at late stages of disease than at earlier stages, the major cause of ovarian cancer deaths is believed to be therapy-resistant metastasis. Although metastasis plays a crucial role in promoting ovarian tumor progression and decreasing patient survival rates, the underlying mechanisms of ovarian cancer spread have yet to be thoroughly explored. For many years, researchers have believed that ovarian cancer metastasizes via a passive mechanism by which ovarian cancer cells are shed from the primary tumor and carried by the physiological movement of peritoneal fluid to the peritoneum and omentum. However, the recent discovery of hematogenous metastasis of ovarian cancer to the omentum via circulating tumor cells instigated rethinking of the mode of ovarian cancer metastasis and the importance of the "seed-and-soil" hypothesis for ovarian cancer metastasis. In this review we discuss the possible mechanisms by which ovarian cancer cells metastasize from the primary tumor to the omentum, the cross-talk signaling events between ovarian cancer cells and various stromal cells that play crucial roles in ovarian cancer metastasis, and the possible clinical implications of these findings in the management of this deadly, highly metastatic disease.

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AutoAnnotate: A Cytoscape app for summarizing networks with semantic annotations

Mike Kucera, Ruth Isserlin, Arkady Arkhangorodsky … (2016)

Networks often contain regions of tightly connected nodes, or clusters, that highlight their shared relationships. An effective way to create a visual summary of a network is to identify clusters and annotate them with an enclosing shape and a summarizing label. Cytoscape provides the ability to annotate a network with shapes and labels, however these annotations must be created manually one at a time, which can be a laborious process. AutoAnnotate is a Cytoscape 3 App that automates the process of identifying clusters and visually annotating them. It greatly reduces the time and effort required to fully annotate clusters in a network, and provides freedom to experiment with different strategies for identifying and labelling clusters. Many customization options are available that enable the user to refine the generated annotations as required. Annotated clusters may be collapsed into single nodes using the Cytoscape groups feature, which helps simplify a network by making its overall structure more visible. AutoAnnotate is applicable to any type of network, including enrichment maps, protein-protein interactions, pathways, or social networks.

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Diagnosis and Management of Ovarian Cancer.

Chyke Doubeni, Anna R B Doubeni, Allison Myers (2016)

Ovarian cancer is the most lethal gynecologic cancer. Less than one-half of patients survive for more than five years after diagnosis. Ovarian cancer affects women of all ages but is most commonly diagnosed after menopause. More than 75% of affected women are diagnosed at an advanced stage because early-stage disease is usually asymptomatic and symptoms of late-stage disease are nonspecific. The strongest risk factors are advancing age and family history of ovarian and breast cancer. Women who have symptoms concerning for ovarian cancer should undergo a physical examination, transvaginal ultrasonography, and measurement of biomarkers such as cancer antigen 125. If results are suspicious for ovarian cancer, the patient should be referred to a gynecologic oncologist. Despite the low rate of early diagnosis, guidelines recommend against routine screening for ovarian cancer in average-risk women because screening, including routine pelvic examinations, is ineffective and associated with harm. However, a recent trial found a potential benefit of annual screening using an algorithm based on serial cancer antigen 125 measurements followed by transvaginal ultrasonography for women at increased risk, as determined by the algorithm. Women with an increased-risk family history should be referred for genetic counseling and, if genetic mutations (e.g., BRCA mutations) are identified, bilateral salpingo-oophorectomy can be considered for risk reduction. In both average- and high-risk women, long-term hormonal contraceptive use reduces risk by about 50%. The treatment of ovarian cancer usually involves surgery, with or without intraperitoneal and intravenous chemotherapy. Primary care physicians have important roles in posttreatment surveillance and end-of-life care.

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Journal

Journal ID (nlm-ta): Int J Mol Sci

Journal ID (iso-abbrev): Int J Mol Sci

Journal ID (publisher-id): ijms

Title: International Journal of Molecular Sciences

Publisher: MDPI

ISSN (Electronic): 1422-0067

Publication date (Electronic): 07 February 2020

Publication date Collection: February 2020

Volume: 21

Issue: 3

Electronic Location Identifier: 1100

Affiliations

[1 ]Department of Toxicology, Poznan University of Medical Sciences, Dojazd 30 St., PL-60-631 Poznan, Poland; andrzej.m.nowicki@ 123456gmail.com (A.N.); malgorzata.jozkowiak@ 123456gmail.com (M.J.); pioramlau@ 123456gmail.com (P.R.); liebert@ 123456ump.edu.pl (J.J.-L.)

[2 ]Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6 St., 60-780 Poznan, Poland; psmrugalska@ 123456ump.edu.pl

[3 ]Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Grunwaldzka 6 St., PL-60-780 Poznan, Poland; mwierzch@ 123456ump.edu.pl

[4 ]Department of Histology and Embryology, Poznan University of Medical Sciences, Swiecickiego 6 St., PL-60-781 Poznan, Poland; marcinruc@ 123456ump.edu.pl

[5 ]Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Swiecickiego 4 St., 60-781 Poznan, Poland; vkrajka@ 123456ump.edu.pl

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[* ]Correspondence: hpiotrow@ 123456ump.edu.pl ; Tel.: +48-61-8470721; Fax: +48-61-8470721

Author information

Paulina Skupin-Mrugalska https://orcid.org/0000-0002-2495-6504

Marcin Rucinski https://orcid.org/0000-0002-2525-5777

Violetta Krajka-Kuzniak https://orcid.org/0000-0001-7275-0298

Article

Publisher ID: ijms-21-01100

DOI: 10.3390/ijms21031100

PMC ID: 7037107

PubMed ID: 32046103

SO-VID: 4598b97a-423a-4b72-bc1a-f5b07b27fe67

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

The Effect of 3′-Hydroxy-3,4,5,4′-Tetramethoxy -stilbene, the Metabolite of the Resveratrol Analogue DMU-212, on the Motility and Proliferation of Ovarian Cancer Cells

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Most cited references 45

Cellular and molecular processes in ovarian cancer metastasis. A Review in the Theme: Cell and Molecular Processes in Cancer Metastasis.

AutoAnnotate: A Cytoscape app for summarizing networks with semantic annotations

Diagnosis and Management of Ovarian Cancer.

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