2′-Benzoyloxycinnamaldehyde-Mediated DJ-1 Upregulation Protects MCF-7 Cells from Mitochondrial Damage

Abstract

2'-Benzoyloxycinnamaldehyde (BCA) is a promising antitumor agent which induces cancer cells apoptosis via reactive oxygen species (ROS) generation. BCA shows more effective antiproliferation in MDA-MB-435 than in MCF-7 breast cancer cells. DJ-1 has been known to protect cells against oxidative stress as an antioxidant because of its cysteine residues sensitive to oxidative stress. In the present study, we evaluated the mechanism of DJ-1 for cell protection from oxidative stress after BCA treatment in MCF-7 cell. BCA upregulates the expression of DJ-1 in MCF-7 cells. However, DJ-1 expression decreased continuously for 24 h after BCA treatment in MDA-MB-435 cells. DJ-1 knockdown sensitized MCF-7 cells to BCA, on the contrary, DJ-1 overexpression induced MDA-MB-435 cells less sensitive to BCA. Confocal microscopic observation showed that only in MCF-7 cells BCA increased the overlapped signal between mitochondria and DJ-1 protein. Mitochondrial membrane potential (MMP) was decreased in MDA-MB-435 cells by BCA, and DJ-1 overexpression inhibited BCA-induced MMP decrease in these cells. On the contrary, DJ-1 knockdown in MCF-7 induced MMP perturbation by BCA. These findings suggest that DJ-1 upregulation protects MCF-7 cells from BCA via inhibiting mitochondrial damage.

Retigeric acid B-induced mitophagy by oxidative stress attenuates cell death against prostate cancer cells in vitro

“…DJ-1 acts as a redox-sensitive chaperone and a sensor for oxidative stress [7] ; it also protects cells against oxidative stress during neuronal injury [8,9] . Furthermore, DJ-1 protects several types of cancer cells, including leukemic [10] , lung carcinoma [11] , and breast cancer [12] cells, from oxidative stress-induced apoptosis. The oxidative stress-induced early translocalization of DJ-1 into mitochondria is closely associated with its cytoprotective activity; DJ-1 is mainly localized in the cytoplasm, but under oxidative stress, it is translocated into mitochondria [13] .…”

DJ-1 upregulates breast cancer cell invasion by repressing KLF17 expression

“…Mitochondrial membrane perturbation, oxidative stress, and proteasome dysfunction are among the several hypotheses suggested to explain the molecular basis of neuronal damage (Dawson and Dawson, 2003). DJ-1 protects several kinds of cancer cells such as pancreatic (Inberg and Linial, 2010), neuronal (Yokota et al , 2003; Zhang et al , 2010), leukaemic (Liu et al , 2008), lung (MacKeigan et al , 2003), and breast (Ismail et al , 2012) against oxidative stress-induced apoptosis. DJ-1 is reported to modulate the PTEN/Akt survival pathway inactivation (Kim et al , 2005).…”

DJ‐1 Protects Breast Cancer Cells Against 2′‐Benzoyloxycinnamaldehyde‐induced Oxidative Stress Independent of Nrf2

“…MCF‐7 is commonly known to be a multi‐drug resistant cancer cell (Chen et al, ). In a previous study, BCA inhibited cell proliferation in both cells, but was more effective in MDA‐MB‐435 (Ismail et al, ). This differential chemosensitivity between MCF‐7 and MDA‐MB‐435 cells to BCA was shown to be due to the mitochondrial DJ‐1 translocation in only MCF‐7 cells after BCA treatment, inducing a protective effect (Ismail et al, ).…”

“…In our previous studies with K‐ras‐transformed cells and isogenic non‐transformed cells (Ock et al, ) and MCF‐7 and MDA‐MB‐435 breast cancer cells (Ismail et al, ), DJ‐1 upregulation was suspected as being a cause of differential cell protection after BCA treatment. In our recent study using breast cancer cells, DJ‐1 protected MCF‐7 cells against BCA‐inducing oxidative stress via its mitochondrial translocation (Ismail et al, ). Therefore, in this study, we tried to uncover the full story behind the protective effect of DJ‐1 in breast cancer cells.…”