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Application of non-invasive low-intensity pulsed electric field with thermal cycling-hyperthermia for synergistically enhanced anticancer effect of chlorogenic acid on PANC-1 cells
- Source :
- PLoS ONE, Vol 15, Iss 1, p e0222126 (2020), PLoS ONE
- Publication Year :
- 2019
- Publisher :
- Cold Spring Harbor Laboratory, 2019.
-
Abstract
- Most existing cancer treatments involve high-cost chemotherapy and radiotherapy, with major side effects, prompting effort to develop alternative treatment modalities. It was reported that the combination of thermal-cycling hyperthermia (TC-HT) and phenolic compound exhibited a moderate cytotoxic effect against human pancreatic cancer PANC-1 cells. In this study, we investigate the efficacy of triple combination in PANC-1 cancer cells by adopting low-intensity pulsed electric field (LIPEF) to couple with TC-HT and CGA (chlorogenic acid). The study finds that this triple combination can significantly impede the proliferation of PANC-1 cells, with only about 20% viable cells left after 24h, whereas being non-toxic to normal cells. The synergistic activity against the PANC-1 cells was achieved by inducing G2/M phase arrest and apoptosis, which were associated with up-regulation of p53 and coupled with increased expression of downstream proteins p21 and Bax. Further mechanism investigations revealed that the cytotoxic activity could be related to mitochondrial apoptosis, characterized by the reduced level of Bcl-2, mitochondrial dysfunction, and sequential activation of caspase-9 and PARP. Also, we found that the triple treatment led to the increase of intracellular reactive oxygen species (ROS) production. Notably, the triple treatment-induced cytotoxic effects and the elevated expression of p53 and p21 proteins as well as the increased Bax/Bcl-2 ratio, all could be alleviated by the ROS scavenger, N-acetyl-cysteine (NAC). These findings indicate that the combination of CGA, TC-HT, and LIPEF may be a promising modality for cancer treatment, as it can induce p53-dependent cell cycle arrest and apoptosis through accumulation of ROS in PANC-1 cells.
- Subjects :
- 0301 basic medicine
Cell cycle checkpoint
medicine.medical_treatment
Cancer Treatment
Apoptosis
Mitochondrion
Biochemistry
Spectrum Analysis Techniques
0302 clinical medicine
Electricity
Medicine and Health Sciences
Enzyme assays
Cytotoxic T cell
Cell Cycle and Cell Division
Colorimetric assays
Bioassays and physiological analysis
Energy-Producing Organelles
Membrane Potential, Mitochondrial
MTT assay
Multidisciplinary
Cell Death
Chemistry
Electromagnetic Radiation
Physics
Flow Cytometry
Mitochondria
Oncology
Electric Field
Cell Processes
Spectrophotometry
030220 oncology & carcinogenesis
Physical Sciences
Medicine
Cytophotometry
Chlorogenic Acid
Cellular Structures and Organelles
Research Article
Hyperthermia
Science
Poly ADP ribose polymerase
Antineoplastic Agents
Bioenergetics
Research and Analysis Methods
Pancreatic Cancer
03 medical and health sciences
Cell Line, Tumor
Pancreatic cancer
Gastrointestinal Tumors
medicine
Humans
Cell Proliferation
Chemotherapy
Biology and Life Sciences
Cancers and Neoplasms
Cancer
Cell Cycle Checkpoints
Hyperthermia, Induced
Cell Biology
medicine.disease
Pancreatic Neoplasms
030104 developmental biology
Cell culture
Biochemical analysis
Cancer cell
Cancer research
Reactive Oxygen Species
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- PLoS ONE, Vol 15, Iss 1, p e0222126 (2020), PLoS ONE
- Accession number :
- edsair.doi.dedup.....ecefdf850de8c637be16740b6f2e794d
- Full Text :
- https://doi.org/10.1101/745562