Enhanced anticancer effects of low-dose curcumin with non-invasive pulsed electric field on PANC-1 cells

Abstract

BackgroundPulsed electric field (PEF) has been considered as a cell permeability enhancing agent for cancer treatment. Nevertheless, application of PEF for conventional electrochemo-therapy is usually at high intensity, and contact or even invasive electrodes are typically used, which may cause unwanted side effects. In this study, a non-invasive way of applying low intensity, non-contact PEF was adopted to study its combination effect with herb, curcumin, against pancreatic cancer cells and the mechanism involved.MethodsThe pancreatic cancer PANC-1 cells were treated with curcumin and PEF alone or in combination, and MTT assay was used to determine the viability of PANC-1 cells. Apoptosis and uptake of curcumin were analyzed by microscopy and flow cytometry. Western blot was further performed to evaluate the expression of apoptotic proteins.ResultsOur results demonstrated that PEF synergized with curcumin to inhibit the proliferation of PANC-1 cells in a field strength- and dose-dependent manner and caused apoptotic death of PANC-1 cells. The apoptotic induction of combination treatment was characterized by an increase in Bax/Bcl-2 ratio, and cleavage of caspase-8, -9, and -3. Moreover, the increase of curcumin uptake via electro-endocytosis was clearly observed in the cells following the exposure of PEF.ConclusionWe show for the first time that a non-contact approach using low intensity electric field in a pulsed waveform could enhance the anticancer effect of low-dose curcumin on PANC-1 cells through triggering both extrinsic and intrinsic pathways. The findings highlight the potential of this alternative treatment, non-invasive electric field and curcumin, to increase therapeutic efficacy with minimum cytotoxicity and side effects, which may provide a new aspect of cancer treatment in combination of PEF and other anticancer agents.

Curcumin- and Piperine-Loaded Emulsomes as Combinational Treatment Approach Enhance the Anticancer Activity of Curcumin on HCT116 Colorectal Cancer Model

“…Our findings are consistent with the previous studies in the literature reporting that curcumin triggers apoptosis in colon cancer cells by activating caspase 3 (Jaiswal et al, 2002;Rashmi et al, 2005;Su et al, 2006;Zhang et al, 2017;Jalili-Nik et al, 2018). Likewise in another study, curcumin therapy on the pancreatic cancer PANC-1 cells resulted in a twofold increase in Caspase 3 gene expression levels indicating once more that the anticancer activity of curcumin proceeds over activation of caspases (Lu et al, 2018). Curcumin is also responsible for directly inducing membrane and DNA degradation and the nuclear shrinkage of cell (Mortezaee et al, 2019).…”

The protective effect of non-invasive low intensity pulsed electric field and fucoidan in preventing oxidative stress-induced motor neuron death via ROCK/Akt pathway

“…The LIPEF device, which we had previously described [ 45 , 46 , 53 ], was used for exposure of the NSC-34 cells to various strength of electric field. The cells were placed between two copper flat and parallel electrodes.…”

“…Therefore, the application of low intensity non-invasive electrical stimulation is a preferred treatment. In fact, we have previously demonstrated that the non-invasive low intensity pulsed electric field (LIPEF) could significantly enhance the anticancer ability of EGCG and curcumin via the synergistic stimulation on the mitochondrial function [ 45 , 46 ]. Given the successful application of LIPEF in cancer treatment, it is believed that multi-frequency components in the LIPEF signal may also induce bioeffects in neuron 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

“…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].…”

“…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]. Our team also observed the consistent effect of non-invasive LIPEF in significantly enhancing EGCG activity in human pancreatic cancer cells [17].…”