Application of non-invasive low strength pulsed electric field to EGCG treatment synergistically enhanced the inhibition effect on PANC-1 cells

Hsieh, Chih-Hsiung; Lu, Chueh‐Hsuan; Chen, Wei‐Ting; Ma, Bo-Lun; Chao, Chih‐Yu

doi:10.1371/journal.pone.0188885

Cited by 15 publications

(22 citation statements)

References 44 publications

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“…These effects basically arise from its abilities to promote pro-apoptotic effects, inhibit angiogenesis, regulate cellular metabolic pathways, and reduce inflammatory factors [28,35]. EGCG can increase the activities of traditional anticancer treatments [36][37][38] and reverse drug cell resistance, and this has encouraged its use in clinical trials for treatments of various types of cancer and other diseases [39]. Acacia catechu Willd.…”

Section: Discussionmentioning

confidence: 99%

Apoptotic-Induced Effects of Acacia Catechu Willd. Extract in Human Colon Cancer Cells

Chiaino

Micucci

Budriesi

et al. 2020

IJMS

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The research for innovative treatments against colon adenocarcinomas is still a great challenge. Acacia catechu Willd. heartwood extract (AC) has health-promoting qualities, especially at the gastrointestinal level. This study characterized AC for its catechins content and investigated the apoptosis-enhancing effect in human colorectal adenocarcinoma HT-29 cells, along with its ability to spare healthy tissue. MTT assay was used to describe the time course, concentration dependence and reversibility of AC-mediated cytotoxicity. Cell cycle analysis and AV-PI and DAPI-staining were performed to evaluate apoptosis, together with ROS formation, mitochondrial membrane potential (MMP) changes and caspase activities. Rat ileum and colon rings were tested for their viability and functionality to explore AC effects on healthy tissue. Quantitative analysis highlighted that AC was rich in (±)-catechin (31.5 ± 0.82 mg/g) and (−)-epicatechin (12.5 ± 0.42 mg/g). AC irreversibly decreased cell viability in a concentration-dependent, but not time-dependent fashion. Cytotoxicity was accompanied by increases in apoptotic cells and ROS, a reduction in MMP and increases in caspase-9 and 3 activities. AC did not affect rat ileum and colon rings' viability and functionality, suggesting a safe profile toward healthy tissue. The present findings outline the potential of AC for colon cancer treatment.3 of 17 at approximately the same content level was observed (Figure 1b). The latter was assumed as a marker of the epimerization as the consequence of the process applied in decoction preparation (thermal treatment). Analysis of decoction preparations stored during very long-term period (at least two years) at room temperature in the dark, did not show loss of (−)-EC and (+)-C, nor epimerization progression, thus suggesting very high chemical stability of the preparation. Int. J. Mol. Sci. 2020, 21, x FOR PEER REVIEW 3 of 17 period (at least two years) at room temperature in the dark, did not show loss of (−)-EC and (+)-C, nor epimerization progression, thus suggesting very high chemical stability of the preparation.

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Section: Discussionmentioning

confidence: 99%

Apoptotic-Induced Effects of Acacia Catechu Willd. Extract in Human Colon Cancer Cells

Chiaino

Micucci

Budriesi

et al. 2020

IJMS

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“…It was found that exposure to non-invasive, low-intensity PEF (LIPEF) has strengthened the effect of low-dose curcumin in combating human pancreatic cancer PANC-1 cells [16]. Our team also observed the consistent effect of non-invasive LIPEF in significantly enhancing EGCG activity in human pancreatic cancer cells [17]. It is noteworthy that LIPEF alone did not harm the cells, underscoring its safety and non-toxicity.…”

Section: Introductionmentioning

confidence: 60%

“…As a viable method in the application of physical stimuli, non-invasive PEF features external application of electric pulse to the desired area. In practice, the use of non-invasive PEF to enhance the activity of anticancer agent and lower the required dosage of agent is significantly effective, as proven by our recent studies on polyphenols with this approach [16,17]. It was found that exposure to non-invasive, low-intensity PEF (LIPEF) has strengthened the effect of low-dose curcumin in combating human pancreatic cancer PANC-1 cells [16].…”

Section: Introductionmentioning

confidence: 99%

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

Kuo

Lin

et al. 2020

PLoS ONE

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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.

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“…The device for exposure of the cells to the PEF was performed as we previously described [ 4 ]. Following the US stimulation, the cells were placed between two copper flat and parallel electrodes.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, we have reported that a non-invasive low strength pulsed electric field (PEF) can enhance the epigallocatechin gallate (EGCG) to combat against the pancreatic cancer cells [ 4 ]. It was found that the synergistic reactions in the double treatment of the EGCG and PEF disturbed the mitochondria, enhanced the intrinsic pathway transduction, and effectively induced apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Studies on the non-invasive anticancer remedy of the triple combination of epigallocatechin gallate, pulsed electric field, and ultrasound

Hsieh

Kuo

et al. 2018

PLoS ONE

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Cancer is one of the most troublesome diseases and a leading cause of death worldwide. Recently, novel treatments have been continuously developed to improve the disadvantages of conventional therapies, such as prodigious expenses, unwanted side effects, and tumor recurrence. Here, we provide the first non-invasive treatment that has combined epigallocatechin gallate (EGCG), the most abundant catechin in green tea, with a low strength pulsed electric field (PEF) and a low energy ultrasound (US). It has been observed that the cell viability of human pancreatic cancer PANC-1 was decreased approximately to 20% of the control after this combination treatment for 72 h. Besides, the combined triple treatment significantly reduced the high tolerance of HepG2 cells to the EGCG-induced cytotoxicity and similarly exhibited compelling proliferation-inhibitory effects. We also found the combined triple treatment increased the intracellular reactive oxygen species (ROS) and acidic vesicles, and the EGCG-induced inhibition of Akt phosphorylation was dramatically intensified. In this study, the apoptosis inhibitor Z-VAD-FMK and the autophagy inhibitor 3-MA were, respectively, shown to attenuate the anticancer effects of the triple treatment. This indicates that the triple treatment-induced autophagy was switched from cytoprotective to cytotoxic, and hence, cooperatively caused cell death with the apoptosis. Since the EGCG is easily accessible from the green tea and mild for a long-term treatment, and the non-invasive physical stimulations could be modified to focus on a specific location, this combined triple treatment may serve as a promising strategy for anticancer therapy.

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Application of non-invasive low strength pulsed electric field to EGCG treatment synergistically enhanced the inhibition effect on PANC-1 cells

Cited by 15 publications

References 44 publications

Apoptotic-Induced Effects of Acacia Catechu Willd. Extract in Human Colon Cancer Cells

Apoptotic-Induced Effects of Acacia Catechu Willd. Extract in Human Colon Cancer Cells

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

Studies on the non-invasive anticancer remedy of the triple combination of epigallocatechin gallate, pulsed electric field, and ultrasound

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