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.

As the most common type of neurodegenerative diseases (NDDs), Alzheimer’s disease (AD) is thought to be caused mainly by the excessive aggregation of β-amyloid protein (Aβ). However, a growing number of studies have found that reactive oxygen species (ROS) play a key role in the onset and progression of AD. The present study aimed to probe the neuroprotective effect of high-frequency low-intensity pulsed electric field (H-LIPEF) for SH-SY5Y cells against hydrogen peroxide (H2O2) and Aβ-induced cytotoxicity. By looking in a systematic way into the frequency- and amplitude-dependent neuroprotective effect of pulsed electric field (PEF), the study finds that H-LIPEF at 200 Hz produces the optimal protective effect for SH-SY5Y cells. The underlying mechanisms were confirmed to be due to the activation of extracellular signal-regulated kinase (ERK) pathway and the downstream prosurvival and antioxidant proteins. Because the electric field can be modified to focus on specific area in a non-contact manner, the study suggests that H-LIPEF holds great potential for treating NDDs, whose effect can be further augmented with the administering of drugs or natural compounds at the same time.

Hyperthermia (HT) has shown feasibility and potency as an anticancer therapy. Administration of HT in the chemotherapy has previously enhanced the cytotoxicity of drugs against pancreatic cancer. However, the drugs used when conducting these studies are substantially conventional chemotherapeutic agents that may cause unwanted side effects. Additionally, the thermal dosage in the treatment of cancer cells could also probably harm the healthy cells. The purpose of this work was to investigate the potential of the two natural polyphenolic compounds, epigallocatechin gallate (EGCG) and chlorogenic acid (CGA), as heat synergizers in the thermal treatment of the PANC-1 cells. Furthermore, we have introduced a unique strategy entitled the thermal cycling-hyperthermia (TC-HT) that is capable of providing a maximum synergy and minimal side effect with the anticancer compounds. Our results demonstrate that the combination of the TC-HT and the CGA or EGCG markedly exerts the anticancer effect against the PANC-1 cells, while none of the single treatment induced such changes. The synergistic activity was attributed to the cell cycle arrest at the G2/M phase and the induction of the ROS-dependent mitochondria-mediated apoptosis. These findings not only represent the first in vitro thermal synergistic study of natural compounds in the treatment of pancreatic cancer, but also highlight the potential of the TC-HT as an alternative strategy in thermal treatment.

With the expansion of the aged population, it is predicted that neurodegenerative diseases (NDDs) will become a major threat to public health worldwide. However, existing therapies can control the symptoms of the diseases at best, rather than offering a fundamental cure. As for the complex pathogenesis, clinical and preclinical researches have indicated that oxidative stress, a central role in neuronal degeneration, is a possible therapeutic target in the development of novel remedies. In this study, the motor neuron-like cell line NSC-34 was employed as an experimental model in probing the effects induced by the combination of non-invasive low intensity pulsed electric field (LIPEF) and fucoidan on the H2O2-induced neuron damage. It was found that single treatment of the LIPEF could protect the NSC-34 cells from oxidative stress, and the protective effect was enhanced by combining the LIPEF and fucoidan. Notably, it was observed that single treatment of the LIPEF obviously suppressed the H2O2-enhanced expression of ROCK protein and increased the phosphorylation of Akt in the H2O2-treated NSC-34 cells. Moreover, the LIPEF can be easily modified to concentrate on a specific area. Accordingly, this technique can be used as an advanced remedy for ROCK inhibition without the drawback of drug metabolism. Therefore, we suggest the LIPEF would be a promising strategy as a treatment for motor neurodegeneration and warrant further probe into its potential in treating other neuronal degenerations.

AbstractNeurodegenerative diseases (NDDs) are becoming a major threat to public health, according to the World Health Organization (WHO). The most common form of NDDs is Alzheimer’s disease (AD), boasting 60-70% share. Excessive aggregation of β-amyloid protein (Aβ) and neurofibrillary tangles has been deemed the major cause for the pathogenesis of AD. A growing number of evidences from studies, however, have suggested that reactive oxygen species (ROS) also play a key role in the onset and progression of AD. Although scientists have had some understanding of the pathogenesis of AD, the disease still cannot be cured, with existing treatment only capable of providing a temporary relief at best, partly due to the obstacle of blood-brain barrier (BBB). The study was aimed to ascertain the neuroprotective effect of thermal cycle hyperthermia (TC-HT) against hydrogen peroxide (H2O2) and Aβ-induced cytotoxicity in SH-SY5Y cells. Treating cells with this physical stimulation beforehand significantly improved the cell viability and decreased the ROS content. The underlying mechanisms were confirmed to be due to the activation of Akt pathway and the downstream antioxidant and prosurvival proteins. The findings manifest significant potential of TC-HT in neuroprotection, via inhibition of oxidative stress and cell apoptosis. It is believed that coupled with the use of drugs or natural compounds, this methodology can be even more effective in treating NDDs.