Open AccessDynamin‐related protein 1‐mediated mitochondrial fission contributes to IR ‐783‐induced apoptosis in human breast cancer cells
Author(s) -
Tang Qin,
Liu Wuyi,
Zhang Qian,
Huang Jingbin,
Hu Changpeng,
Liu Yali,
Wang Qing,
Zhou Min,
Lai Wenjing,
Sheng Fangfang,
Li Guobing,
Zhang Rong
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13749
Subject(s) - mitochondrial fission , dnm1l , mitochondrial permeability transition pore , mitochondrial apoptosis induced channel , mitochondrion , microbiology and biotechnology , apoptosis , biology , fis1 , mfn1 , mitochondrial fusion , dnaja3 , cancer cell , cytochrome c , programmed cell death , chemistry , cancer , mitochondrial dna , biochemistry , genetics , gene
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 ( OPA 1). 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.