Bik subcellular localization in response to oxidative stress induced by chemotherapy, in Two different breast cancer cell lines and a Non‐tumorigenic epithelial cell line

Abstract

Cancer chemotherapy remains one of the preferred therapeutic modalities against malignancies despite its damaging side effects. An expected outcome while utilizing chemotherapy is apoptosis induction. This is mainly regulated by a group of proteins known as the Bcl-2 family, usually found within the endoplasmic reticulum or the mitochondria. Recently, these proteins have been located in other sites and non-canonic functions have been unraveled. Bik is a pro-apoptotic protein, which becomes deregulated in cancer, and as apoptosis is associated with oxidative stress generation, our objective was to determine the subcellular localization of Bik either after a direct oxidative insult due to H2 O2 , or indirectly by cisplatin, an antineoplastic agent. Experiments were performed in two human transformed mammary gland cell lines MDA-MB-231 and MCF-7, and one non-tumorigenic epithelial cell line MCF-10A. Our results showed that in MCF-7, Bik is localized within the cytosol and that after oxidative stress treatment it translocates into the nucleus. However, in MDA-MB-231, Bik localizes in the nucleus and translocates to the cytosol. In MCF10A Bik did not change its cellular site after either treatment. Interestingly, MCF10A were more resistant to cisplatin than transformed cell lines. This is the first report showing that Bik is located in different cellular compartments depending on the cancer stage, and it has the ability to change its subcellular localization in response to oxidative stress. This is associated with increased sensitivity when exposed to toxic agents, thus rendering novel opportunities to study new therapeutic targets allowing the development of more active and less harmful agents.

<div>Epigenetic memory of oxidative stress: does nephrilin exert its protective effects via Rac1?</div>

“…It is notable that the elevation of Bik was previously shown to correlate with oxidative stress 20,21. These results are consistent with and supportive of our main hypothesis.…”

Star-PAP, a poly(A) polymerase, functions as a tumor suppressor in an orthotopic human breast cancer model

“…Through changing its subcellular localization, BIK is involved in response to oxidative stress caused by chemotherapy in several breast cancer cell lines. 27 Moreover, BIK controls the expression of miRNAs as well as the autophagic flux in MDA-MB-231 cells. 28 Thus, it would be interesting to investigate whether Star-PAP is involved in these new functions of BIK.…”

Cytotoxic activity of physodic acid and acetone extract fromHypogymnia physodesagainst breast cancer cell lines

“…According to a recent study, a broad spectrum of mechanisms may be responsible for the resistance of MCF-10A cells to anticancer compounds. These include differences in the subcellular localization of Bik (Trejo-Vargas et al 2015) and the KLF8/EGFR signalling pathway (Li et al 2015), differences in stearoyl-CoA desaturase-1 activity (Belkaid et al 2015) and combined inhibition by glycolysis and AMP-activated protein kinase (Wu et al 2015), and differences in mitochodrial-mediated apoptosis (Taha et al 2015). Therefore, the exact mechanism responsible for the selective activity of physodic acid in breast cancer should be further investigated.…”