The histone deacetylase inhibitor OBP-801 and eribulin synergistically inhibit the growth of triple-negative breast cancer cells with the suppression of survivin, Bcl-xL, and the MAPK pathway

Breast Cancer Research and Treatment
Hisako OnoToshiyuki Sakai

Abstract

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Eribulin was approved for the treatment of metastatic breast cancer through the EMBRACE trial, and a subgroup analysis in this clinical trial indicated the efficacy of eribulin in patients with TNBC. However, the prognosis of patients with TNBC is still poor due to various molecular characteristics. Therefore, there is an urgent need for a more effective treatment for the management of TNBC. We investigated the synergistic effect of a novel histone deacetylase (HDAC) inhibitor, OBP-801, and eribulin in TNBC cell lines because OBP-801 has been known to enhance the anti-tumor activities of other chemotherapeutic agents. The cell growth was analyzed, and the flow cytometry analysis was conducted to evaluate the effects on cell cycle and the induction of apoptosis. The mechanism underlying the enhancement of inhibition of TNBC cell growth was investigated through Western blot analyses. The combination treatment of OBP-801 with eribulin showed the synergistic inhibition of the growth in TNBC cells, involved with the enhancement of apoptosis. We, for the first time, found that eribulin upregulated survivin and also that OBP-801 could remarkably supp...Continue Reading

References

Aug 1, 1997·Nature Medicine·G AmbrosiniD C Altieri
Aug 2, 2002·Cancer Cell·Daniel S O'ConnorDario C Altieri
Aug 2, 2003·Cancer Cell·Ricky W Johnstone, Jonathan D Licht
Oct 26, 2005·Proceedings of the National Academy of Sciences of the United States of America·Yan ZhaoQiang Yu
Jan 13, 2006·Annals of Oncology : Official Journal of the European Society for Medical Oncology·B M RyanM J Duffy
Jun 11, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michael Bots, Ricky W Johnstone
Mar 8, 2011·Lancet·Javier CortesUNKNOWN EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389) investigators
May 23, 2012·Breast Cancer Research : BCR·Chandra R TateBridgette M Collins-Burow
Aug 19, 2014·Breast Cancer Research and Treatment·Amy PlotkinDorraya El-Ashry
Nov 9, 2014·Breast Cancer Research and Treatment·Chris TwelvesAhmad Awada
Jul 15, 2015·Journal of Hematology & Oncology·Min-Wu ChaoChe-Ming Teng
Jun 15, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anderly C ChüehJohn M Mariadason
Jul 1, 2017·The Breast : Official Journal of the European Society of Mastology·Kazuhiro ArakiYoshinori Ito

❮ Previous
Next ❯

Citations

Jan 24, 2019·Korean Journal of Radiology : Official Journal of the Korean Radiological Society·Sung Hun KimUNKNOWN Alliance for Breast Cancer Screening in Korea (ABCS-K)
Sep 1, 2019·Cellular and Molecular Life Sciences : CMLS·Jin ZhangZhengmao Zhu
Jul 2, 2020·Journal of Medicinal Chemistry·Terence C S HoA Ganesan
Apr 13, 2021·Journal of Biomedical Science·Kunal Nepali, Jing-Ping Liou
Aug 7, 2021·Journal of Personalized Medicine·Christos DamaskosDimitrios Dimitroulis

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cell Cycle Pathways

Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.

Breast Cancer Triple-N

Breast cancer cells have receptors for estrogen, progesterone, HER2 receptors (also called ERBB2). Triple-negative breast cancers do not have any of these receptors. Here are the latest discoveries pertaining to triple-negative breast cancers.

Breast Cancer: Chemo-Resistance

Some cancers are difficult to treat and aggressive including the "triple-negative" breast cancer. This type of cancer is chemoresistant even before chemotherapy begins. Here are the latest discoveries chemo-resistance in breast cancer.

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.