Application of non-invasive low-intensity pulsed electric field with thermal cyclinghyperthermia for synergistically enhanced anticancer effect of chlorogenic acid on PANC-1 cells
Journal
PLoS ONE
Journal Volume
15
Journal Issue
1
Pages
-
Date Issued
2020
Author(s)
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 nontoxic 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. ? 2020 Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
SDGs
Other Subjects
acetylcysteine; caspase 9; chlorogenic acid; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; protein Bax; protein bcl 2; protein p21; protein p53; reactive oxygen metabolite; antineoplastic agent; chlorogenic acid; reactive oxygen metabolite; antineoplastic activity; apoptosis; Article; bioaccumulation; cell proliferation; cell viability; clinical effectiveness; controlled study; cytotoxicity; disorders of mitochondrial functions; drug effect; drug efficacy; drug mechanism; drug response; G2 phase cell cycle checkpoint; human; human cell; low intensity pulsed electric field; mitochondrial membrane potential; PANC-1 cell line; protein expression; pulsed electric field; synergistic effect; temperature related phenomena; thermal cycling hyperthermia; upregulation; cell cycle checkpoint; electromagnetic radiation; metabolism; mitochondrion; pancreas tumor; pathology; procedures; thermotherapy; tumor cell line; Antineoplastic Agents; Apoptosis; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Chlorogenic Acid; Electromagnetic Radiation; Humans; Hyperthermia, Induced; Membrane Potential, Mitochondrial; Mitochondria; Pancreatic Neoplasms; Reactive Oxygen Species
Type
journal article