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.
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 ef...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0222126 |
| _version_ | 1818678040521080832 |
|---|---|
| author | Chueh-Hsuan Lu Yu-Yi Kuo Guan-Bo Lin Wei-Ting Chen Chih-Yu Chao |
| author_facet | Chueh-Hsuan Lu Yu-Yi Kuo Guan-Bo Lin Wei-Ting Chen Chih-Yu Chao |
| author_sort | Chueh-Hsuan Lu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T09:08:57Z |
| format | Article |
| id | doaj.art-b6c32725800c4cebb0cb4340e86753b0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T09:08:57Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b6c32725800c4cebb0cb4340e86753b02022-12-21T21:55:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01151e022212610.1371/journal.pone.0222126Application of non-invasive low-intensity pulsed electric field with thermal cycling-hyperthermia for synergistically enhanced anticancer effect of chlorogenic acid on PANC-1 cells.Chueh-Hsuan LuYu-Yi KuoGuan-Bo LinWei-Ting ChenChih-Yu ChaoMost 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.https://doi.org/10.1371/journal.pone.0222126 |
| spellingShingle | Chueh-Hsuan Lu Yu-Yi Kuo Guan-Bo Lin Wei-Ting Chen Chih-Yu Chao 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. PLoS ONE |
| title | 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. |
| title_full | 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. |
| title_fullStr | 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. |
| title_full_unstemmed | 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. |
| title_short | 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. |
| title_sort | 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 |
| url | https://doi.org/10.1371/journal.pone.0222126 |
| work_keys_str_mv | AT chuehhsuanlu applicationofnoninvasivelowintensitypulsedelectricfieldwiththermalcyclinghyperthermiaforsynergisticallyenhancedanticancereffectofchlorogenicacidonpanc1cells AT yuyikuo applicationofnoninvasivelowintensitypulsedelectricfieldwiththermalcyclinghyperthermiaforsynergisticallyenhancedanticancereffectofchlorogenicacidonpanc1cells AT guanbolin applicationofnoninvasivelowintensitypulsedelectricfieldwiththermalcyclinghyperthermiaforsynergisticallyenhancedanticancereffectofchlorogenicacidonpanc1cells AT weitingchen applicationofnoninvasivelowintensitypulsedelectricfieldwiththermalcyclinghyperthermiaforsynergisticallyenhancedanticancereffectofchlorogenicacidonpanc1cells AT chihyuchao applicationofnoninvasivelowintensitypulsedelectricfieldwiththermalcyclinghyperthermiaforsynergisticallyenhancedanticancereffectofchlorogenicacidonpanc1cells |