Thermal cycling-hyperthermia in combination with polyphenols, epigallocatechin gallate and chlorogenic acid, exerts synergistic anticancer effect against human pancreatic cancer PANC-1 cells

Abstract

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 novel 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 thermal synergistic study of natural compounds in the treatment of pancreatic cancer, but also highlight the potential application of the TC-HT as an alternative strategy in anticancer treatment.

Potential Therapeutic Targets of Epigallocatechin Gallate (EGCG), the Most Abundant Catechin in Green Tea, and Its Role in the Therapy of Various Types of Cancer

“…The combination of the thermal cycling-hyperthermia and the chlorogenic acid or Epigallocatechin gallate significantly cause the anticancer effect against pancreatic cancer, whereas none of the single treatment induced such types of changes. The synergistic activity was credited to the cell cycle arrest at the G 2 /M phase and the induction of the reactive oxygen species-dependent mitochondria-mediated apoptosis [ 70 ]. A pioneering study was undertaken to evaluate how Epigallocatechin gallate targets the metabolism of pancreatic adenocarcinoma cells.…”

Chlorogenic acid depresses cellular bioenergetics to suppress pancreatic carcinoma through modulating c‐Myc‐TFR1 axis

“…It was previously found that CA exhibited potential anti‐tumor activity in PDAC cell line PANC‐1 cells (Lu, Chen, Hsieh, Kuo, & Chao, 2019). However, the intrinsic mechanism remains largely unknown.…”

The impact of the co‐exposure of melanoma cells to chlorogenic acid and a moderate‐strength static magnetic field

“…The latter depend on the concentration of these compounds and the conditions of the experiment as was observed in the studies of Gomes et al (2003). The growth inhibitory effect of phenolic acids on many cancer cell lines such as human colon cancer cells (Rosa et al., 2016), human cervical cancer cells (HeLa cells) (Senawong et al., 2014), human hepatocellular carcinoma cells (HepG2) (Liu et al., 2019; Yan et al., 2017), and human pancreatic cancer cells (PANC‐1) (in combination with thermal cycling‐hyperthermia) (Lu et al., 2019) has also been observed. The mechanisms of such action were associated with the suppression of cell growth, the activation of apoptosis, a redox imbalance in the tumor cells and other pathways such as the MAPK signaling pathway, the AMP‐activated protein kinase (AMPK) pathway and the HIF‐1a/AKT pathway (Lukitasari et al., 2018).…”