[논문]Pulsed electromagnetic field potentiates etoposide-induced MCF-7 cell death

Woo, Sung-Hun; Kim, Bohee; Kim, Sung Hoon; Jung, Byung Chul; Lee, Yongheum; Kim, Yoon Suk

doi:10.5483/bmbrep.2022.55.3.119

Pulsed electromagnetic field potentiates etoposide-induced MCF-7 cell death 원문보기

BMB reports, v.55 no.3, 2022년, pp.148 - 153

Woo, Sung-Hun (Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University) , Kim, Bohee (Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University) , Kim, Sung Hoon (Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University) , Jung, Byung Chul (Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University) , Lee, Yongheum (Department of Biomedical Engineering, College of Software and Digital Healthcare Convergence, Yonsei University) , Kim, Yoon Suk (Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University)

Abstract ▼ AI-Helper

Etoposide is a chemotherapeutic medication used to treat various types of cancer, including breast cancer. It is established that pulsed electromagnetic field (PEMF) therapy can enhance the effects of anti-cancer chemotherapeutic agents. In this study, we investigated whether PEMFs influence the anti-cancer effects of etoposide in MCF-7 cells and determined the signal pathways affected by PEMFs. We observed that co-treatment with etoposide and PEMFs led to a decrease in viable cells compared with cells solely treated with etoposide. PEMFs elevated the etoposide-induced PARP cleavage and caspase-7/9 activation and enhanced the etoposide-induced down-regulation of survivin and up-regulation of Bax. PEMF also increased the etoposide-induced activation of DNA damage-related molecules. In addition, the reactive oxygen species (ROS) level was slightly elevated during etoposide treatment and significantly increased during co-treatment with etoposide and PEMF. Moreover, treatment with ROS scavenger restored the PEMF-induced decrease in cell viability in etoposide-treated MCF-7 cells. These results combined indicate that PEMFs enhance etoposide-induced cell death by increasing ROS induction-DNA damage-caspase-dependent apoptosis.

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표/그림 (4)

그림 Fig. 1. Increase of etoposide-induced MCF-7 cell death in response to PEMF stimulation. MCF-7 cells were treated with (A) 100 μM amentoflavone (AMF), (B) 0.5 mM cyclophosphamide (CPA), (C) 10 nM methotrexate (MET), and (D) 1 μM etoposide (ETO) followed by incubation for 2 days. The treated cells were stimulated with or without a 1 h PEMF session (2.5 mT at 70 Hz) thrice a day for 2 days. (E) MCF-7 cells were treated with 1 μM etoposide and maintained for the indicated periods (12, 24, or 48 h). Etoposide- treated cells were stimulated with or without PEMF for the indicated periods. Subsequently, cell viability was analyzed. The Con group indicates non-treated cells. The PEMF group (PEMF) indicates cells stimulated with PEMF only. The Drug group (e.g. ETO) indicates cells stimulated with an anti-cancer drug alone, and the Drug + P group (e.g. ETO + P) indicates cells treated with anticancer drugs and PEMF. The number of viable cells in the control group was set as 100%. Data were the mean ± SEM of three independent experiments. P values were determined using Student's t-test (ns, not significant, **P < 0.05 and ***P < 0.001).
그림 Fig. 2. PEMF-induced increased activation of apoptotic molecules in etoposide-treated MCF-7 cells. MCF-7 cells were treated with the 1 μM of etoposide and exposed to PEMFs for 2 days. During this period, cells were harvested for protein preparation at the times indicated (0 h, 12 h, 24 h, and 48 h after treatment with ETO). (A) PARP cleavage, (B) activation of caspase-3 and -7, (C) activation of caspase-8 and -9, (D) survivin and XIAP protein levels, (E) amounts of PUMA, AIF, Bax, phosphorylated BAD and Bcl-2 were analyzed using western blot assay. GAPDH was used as an internal control.
그림 Fig. 3. PEMF-induced enhanced phosphorylation of DNA damage-related molecules in etoposide-treated MCF-7 cells. 1 μM etoposide was used to treat MCF-7 cells. Subsequently, the cells were exposed to PEMFs for the indicated times (0 h, 12 h, 24 h after treatment with ETO). Phosphorylation of (A) H2AX, (B) Chk-1 and Chk-2, and (C) ATM and ATR, were analyzed using western blot assay. 1 μM etoposide with or without 5 μM ATM inhibitor were used to treat MCF-7 cells. Cells were then exposed to PEMFs for 24 h. Phosphorylation levels of (D) Chk1, Chk2, and H2AX, (E) expression level of survivin and cleavage of caspase-9, caspase-7, and PARP were analyzed by western blot assay.
그림 Fig. 4. Increase of etoposide-induced MCF-7 cell death by PEMFstimulated up-regulation of intracellular ROS. MCF-7 cells were treated with 1 μM etoposide and maintained for 2 days. During this incubation period, cells were stimulated with or without PEMFs. The cells were stained with DCF-DA and the fluorescence intensity, displayed as (A) histogram and (B) bar graph, was determined by flow cytometry. The fluorescence intensity of the Con group was set to 101. Data were the mean ± SEM of three independent experiments. P values were determined using Student’s t-test (ns, not significant, and ***P < 0.001). MCF-7 cells were treated with 1 μM etoposide in the presence or absence of 10 μM ROS scavenger (NAC) and exposed to PEMFs for 12 h. (C) The phosphorylation of Chk1, Chk2, and H2AX; (D) expression of Bax and survivin; and cleavage of caspase-7, caspase-9, and PARP were analyzed by western blotting. (E) MCF-7 cells were treated with the 1 μM etoposide in the presence or absence of 1, 5, or 10 μM ROS scavenger (NAC) and exposed to PEMFs for 48 h. Cell viability analysis was performed. The cell viability of Con group was set to 100%. Data were the mean ± SEM of three independent experiments. P values were determined using Student’s t-test (ns, not significant and ***P < 0.001).

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표제어: PCR

동의어: Packet Collision Rate

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