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Mechanical stress-induced cell death in breast cancer cells.

ABSTRACT: Providing an external mechanical stress to cancer cells seems to be an effective approach to treat cancer locally. Numbers of reports on cancer cell death subjected to mechanical stress loading are increasing, but they are more focused on apoptosis. Inducing necrosis is also important in attracting more immune cells to the cancer site via the release of danger-associated molecular patterns from cancer cells. Here we applied dynamic compression to breast cancer cells with a low frequency (0.1-30 Hz) and for a short duration (30-300 s) and they resulted in a mixed mode of apoptosis and necrosis dominant with necrotic cell death, which we call mechanical stress-induced cell death (MSICD). The necrotic cell damage of mechanically treated breast cancer cells increased in a force-dependent and time-dependent manner while a trend of frequency-independent MSICD was observed.

SUBMITTER: Takao S

PROVIDER: S-EPMC6737978 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Mechanical stress-induced cell death in breast cancer cells.

Takao Satomi S Taya Minoru M Chiew Cerwyn C

Biology open 20190816 8

Providing an external mechanical stress to cancer cells seems to be an effective approach to treat cancer locally. Numbers of reports on cancer cell death subjected to mechanical stress loading are increasing, but they are more focused on apoptosis. Inducing necrosis is also important in attracting more immune cells to the cancer site via the release of danger-associated molecular patterns from cancer cells. Here we applied dynamic compression to breast cancer cells with a low frequency (0.1-30 ...[more]

PMID: 31362953

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Project description:Bioactive compounds from plants represent good candidate drugs for the prevention and treatment of various forms of cancer. Berries are rich sources of bioactive compounds, and there has been an increasing interest in the study of therapeutic action of wild berries. Oxidants are generated continuously in biological system as a result of physiological process. When there is an imbalance between oxidants and antioxidants, it leads to a condition called oxidative stress. Natural compounds as inducers of oxidative stress are able to modulate the physiological functions of cancer cells leading to cell death or survival. The aim of this study was to evaluate the induction of apoptosis by isolated bioactive compounds (1-(2-hydroxyphenyl)-4-methylpentan-1-one (C1) and 2-[(3-methylbutoxy) carbonyl] benzoic acid (C2)) from Rubus fairholmianus against MCF-7 breast cancer cells. The exposure of C1 and C2 reduced viability (IC50 of C1: 4.69; C2: 8.36 μg/mL) and proliferation. Cytochrome c release from mitochondria and changes in mitochondrial membrane potential of treated cells supported the intrinsic apoptotic cell death. Reactive oxygen species (ROS) production after treatment with C1 and C2 was found to be higher and induced nuclear damage. Expression of apoptotic proteins after the treatments was significantly upregulated as indicated using immunofluorescence (caspase 9, p53, and Bax), western blotting (p53, cleaved PARP, cytochrome c, and Bax), and ELISA (caspase 9) analysis. Overall, C1 was more cytotoxic, increased the ROS production in dichlorodihydrofluorescein diacetate assay, and induced apoptosis in breast cancer cells. These results illustrate that berry bioactive compounds have strong chemopreventive potential. In this article, we provide information on prooxidant and anticancer activities of Rubus bioactive compounds. Natural products have always demonstrated a significant contribution to the development of several cancer chemotherapeutic drugs. Most of these compounds are known to affect the redox state of the cell; and studies on these compounds have focused on their antioxidant property instead of prooxidant properties.

Project description:In radiation oncology, ionizing radiation is used to kill cancer cells, in other words, the induction of different types of cell death. To investigate this cellular death and the associated iron accumulation, the transfer, release, and participation of iron after radiation treatment was analyzed. We found that radiation-induced cell death varied in different breast cancer cells and autophagy was induced in MDA-MB-231 and BT549 cells (triple negative breast cancer cell line) rather than in MCF-7 and zr-75 cells. Iron chelator deferoxamine (DFO), the autophagy inhibitor 3MA, silencing of the autophagy-related genes ATG5, and Beclin 1 could decrease radiation induced cell death in MDA-MB-231 cells, while inhibitors of apoptosis such as Z-VAD-FMK, ferroptosis inhibitor ferrostatin-1 (Fer-1), and necroptosis inhibitor Necrostatin-1 showed no change. This suggests the occurrence of autophagic cell death. Furthermore, we found that iron accumulation and iron regulatory proteins, including transferrin (Tf), transferrin receptor (CD71), and Ferritin (FTH), increased after radiation treatment, and the silencing of transferrin decreased radiation-induced cell death. In addition, radiation increased lysosomal membrane permeabilization (LMP) and the release of lysosomal iron and cathepsins, while cathepsins silencing failed to change cell viability. Radiation-induced iron accumulation increased Reactive oxygen species (ROS) generation via the Fenton reaction and increased autophagy in a time-dependent manner. DFO, N-acetylcysteine (NAC), and overexpression of superoxide dismutase 2 (SOD2) decreased ROS generation, autophagy, and cell death. To summarize, for the first time, we found that radiation-induced autophagic cell death was iron-dependent in breast cancer MDA-MB-231 cells. These results provide new insights into the cell death process of cancers and might conduce to the development and application of novel therapeutic strategies for patients with apoptosis-resistant breast cancer.

Dataset Information

Mechanical stress-induced cell death in breast cancer cells.

Publications

Mechanical stress-induced cell death in breast cancer cells.

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