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  • Dynamin-related protein 1-mediated mitochondrial fission contributes to IR-783-induced apoptosis in human breast cancer cells.

Dynamin-related protein 1-mediated mitochondrial fission contributes to IR-783-induced apoptosis in human breast cancer cells.

Journal of cellular and molecular medicine (2018-07-12)
Qin Tang, Wuyi Liu, Qian Zhang, Jingbin Huang, Changpeng Hu, Yali Liu, Qing Wang, Min Zhou, Wenjing Lai, Fangfang Sheng, Guobing Li, Rong Zhang
ABSTRACT

IR-783 is a kind of heptamethine cyanine dye that exhibits imaging, cancer targeting and anticancer properties. A previous study reported that its imaging and targeting properties were related to mitochondria. However, the molecular mechanism behind the anticancer activity of IR-783 has not been well demonstrated. In this study, we showed that IR-783 inhibits cell viability and induces mitochondrial apoptosis in human breast cancer cells. Exposure of MDA-MB-231 cells to IR-783 resulted in the loss of mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) depletion, mitochondrial permeability transition pore (mPTP) opening and cytochrome c (Cyto C) release. Furthermore, we found that IR-783 induced dynamin-related protein 1 (Drp1) translocation from the cytosol to the mitochondria, increased the expression of mitochondrial fission proteins mitochondrial fission factor (MFF) and fission-1 (Fis1), and decreased the expression of mitochondrial fusion proteins mitofusin1 (Mfn1) and optic atrophy 1 (OPA1). Moreover, knockdown of Drp1 markedly blocked IR-783-mediated mitochondrial fission, loss of MMP, ATP depletion, mPTP opening and apoptosis. Our in vivo study confirmed that IR-783 markedly inhibited tumour growth and induced apoptosis in an MDA-MB-231 xenograft model in association with the mitochondrial translocation of Drp1. Taken together, these findings suggest that IR-783 induces apoptosis in human breast cancer cells by increasing Drp1-mediated mitochondrial fission. Our study uncovered the molecular mechanism of the anti-breast cancer effects of IR-783 and provided novel perspectives for the application of IR-783 in the treatment of breast cancer.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Puromycin dihydrochloride, Ready Made Solution, from Streptomyces alboniger, 10 mg/mL in H2O, 0.2 μm filtered
Sigma-Aldrich
Adenosine 5′-diphosphoribose sodium salt, ≥93%
Sigma-Aldrich
IR-783, Dye content 90 %
Sigma-Aldrich
MISSION® esiRNA, targeting human DNM1L