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BMC Cancer. 2015 Nov 3;15:838. doi: 10.1186/s12885-015-1850-4.

Targeting glycolysis by 3-bromopyruvate improves tamoxifen cytotoxicity of breast cancer cell lines.

Author information

1
Pharmacology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Kasr Al Eini Street, Fom El Khalig, Cairo, Egypt, 11796. Yasmin.m.attia@gmail.com.
2
Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini St, Cairo, Egypt, 11562. hanan.elabhar@pharma.cu.edu.eg.
3
Pharmacology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Kasr Al Eini Street, Fom El Khalig, Cairo, Egypt, 11796. mahmoud.almarzanani@nci.cu.edu.eg.
4
Pharmacology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Kasr Al Eini Street, Fom El Khalig, Cairo, Egypt, 11796. samia.shouman@nci.cu.edu.eg.

Abstract

BACKGROUND:

Tamoxifen is the standard endocrine therapy for ER+ breast cancer; however, many women still relapse after long-term therapy. 3-Bromopyruvate, a glycolytic inhibitor, has shown high selective anti-tumor activity in vitro, and in vivo. The aim of this study was to evaluate the possible augmentation of the effect of tamoxifen via reprograming cancer cell metabolism using 3-bromopyruvate.

METHODS:

An in vitro screening of antitumor activity as well as the apoptotic, anti-metastatic, and anti-angiogenic potentials of the combination therapy were carried out using different techniques on breast cancer cell lines MCF7and T47D. In addition the antitumor effect of the combined therapy was done on mice bearing tumor.

RESULTS:

Our results showed modulation in apoptosis, angiogenesis and metastatic potential by either drug alone; however, their combination has surpassed that of the individual one. Combination regimen enhanced activated caspases-3, 7 and 9, as well as oxidative stress, signified by increased malondialdehyde and decreased glutathione level. Additionally, the angiogenesis and metastasis markers, including hypoxia inducing factor-1α, vascular endothelia growth factor, and metaloproteinases-2 and 9 were decreased after using the combination regimen. These results were further confirmed by the in vivo study, which depicted a decrease in the tumor volume and angiogenesis and an increase in oxidative stress as well.

CONCLUSION:

3-bromopyruvate could be a valuable compound when added with tamoxifen in breast cancer treatment.

PMID:
26526196
PMCID:
PMC4630933
DOI:
10.1186/s12885-015-1850-4
[Indexed for MEDLINE]
Free PMC Article

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