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

Abstract

BackgroundTamoxifen 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.MethodsAn 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.ResultsOur 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.Conclusion3-bromopyruvate could be a valuable compound when added with tamoxifen in breast cancer treatment.

Anticancer potentiality of lignan rich fraction of six Flaxseed cultivars

“…The reduction of P53 expression in flaxseed- treated T47D while upregulation of expression in MCF7 treated cells is advantageous for both cell lines as T47D cells has mutant P53 and MCF7 has wild type P53. These data are in agreement with those reported before, which stated that mutant p53 silencing which specifically targets mutant p53 in T47D cells induced massive apoptosis as evidenced by morphological cell blebbing, PARP cleavage, and annexin V/PI staining, however, apoptosis was not observed in MCF-7 or MCF-10A cells that express only wild type 20 , 30 .…”

“…Our results showed that PFH-G9 significantly attenuated MMP-2 and MMP-9 levels in T47D cells although, TAM an estrogen receptor modulator used in ER positive breast cancer patients treatment significantly enhanced MMP-2 and MMP-9 levels in T47D cells. Similar upregulation of MMP2 and 9 by TAM in T47D cells was previously reported 20 . The decreased levels of MMP-2 and 9 in this study cope well with a previous study which revealed that enterolactone, a mammalian lignan derived from flaxseed down-regulated the metastasis-related MMP-2, MMP-9 and MMP-14 gene expressions in MCF-7 and MDA-MB231 cell lines 2 .…”

Caveolin-1 inhibits breast cancer stem cells via c-Myc-mediated metabolic reprogramming

“…In the present study, we found that 3-BrPA could induce Cav-1 expression and therefore inhibit the BCSCs selfrenewal in RAS-transformed MCF-10A cells and breast cancer MCF-7 cells. It has also been reported that 3-BrPA treatment alone showed excellent antitumor activities in breast cancer xenografts and could sensitize breast cancer tumor to chemotherapy via reprogramming cancer metabolism 33,34 . What is more, our previous study identified betulinic acid as an inducer of Cav-1 expression in breast cancer cells 35 .…”

Cytotoxic effects of tamoxifen in breast cancer cells

“…For example, caspase-8 and -9 are known as initiator caspases, while caspase-3, -6, and -7 are known as executioner caspases [16] . Progress has been made in the early diagnosis and treatment of cancer, and in particular, breast cancer [18][19][20][21][22] . The MCF7 cancer cell line can be used to sensitively detect the response of estrogen [23,24] .…”