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 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.

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

“…Notably, the level of p21 proteins was also increased after treatment of PANC-1 cells with triple combination (Fig 6). Furthermore, a recent study of our team showed that the combination treatment of PANC-1 cells with CGA and TC-HT can induce cell cycle arrest via suppression of Cdc2 and cyclin B1 [7]. Therefore, it is judged the suppression of cell proliferation by triple treatment involves a cell cycle arrest during G2/M phase.…”

“…The experimental setup and administration of TC-HT (10-cycles) have been previously described [7] with optimum results. The TC-HT was performed by using a modified PCR system to achieve a series of short period of heat exposure within the desired time.…”

“…The physical stimuli not only have potential advantages of providing non-invasiveness and safety, but also can be controlled in a precise manner to obtain a non-harmful means toward non-cancerous cells. We have recently shown that the thermal cycling-hyperthermia (TC-HT) combined with chlorogenic acid (CGA) has an anticancer synergy in combating human pancreatic cancer PANC-1 cells [7], but the effect is moderate. On the other hand, previously, the incorporation of pulsed electric field (PEF) into triple remedy has been demonstrated to potentiate the cytotoxicity of double combination of ultrasound and herb by our group [8].…”

Mapping Pharmacological Network of Multi-Targeting Litchi Ingredients in Cancer Therapeutics

“…pancreatic and colon cancer (Baek et al, 2004;Lim et al, 2006;Kürbitz et al, 2011;Cordero-Herrera et al, 2013) (Sukhthankar et al, 2010;Kuerbitz et al, 2011;Wang et al, 2011b;Lee et al, 2012;Luo et al, 2014;Fu et al, 2019) attenuating angiogenesis MPI, ACTA1, PECAM1 lung cancer (Deng et al, 2019) inhibiting metastasis CDH1/2, CSRC, ERBB2, ESR2, MAPK8, MIR138, NFKB, PTK2, SLC22A5, SNAIL1/2, TJP1, VIM, lung, colon, breast, bladder, and prostate cancer (Shimizu et al, 2005a;Punathil et al, 2008;Sen et al, 2010;Sen and Chatterjee, 2011;Deng and Lin, 2011;Ko et al, 2013;Mukherjee et al, 2014;Li et al, 2015;Huang et al, 2016b;Luo et al, 2017) promoting apoptosis and autophagy AKT1, AP1, APAF1, ATM, BAD, BAX, BCL2/L1, BIRC5, CASP2/3/8/9, CCNB1, CDC2, CDKN1A, CYC, DIABLO, EGFR, ERBB2/3, FAS, FASLG, GDF15, JNK1/2, KRAS, MAPK1/14, MLH1, MSH2, MTCO2, MYC, NFKB, PARP1, PEG2, PGE2, PIK3CA, PRKAA2, PTEN, PTK2, SP1, TP53 pancreatic, lung, colon, head and neck, breast, and bladder cancer (Shimizu et al, 2005b;Park et al, 2009;Deng and Lin, 2011;Kang et al, 2013;Cerezo-Guisado et al, 2015;Li et al, 2016;Luo et al, 2017;Huang et al, 2017;Ni et al, 2018;Gu et al, 2018;Wei et al, 2018;Lu et al, 2019) sensitizing chemotherapy ABCG2/B1, ATP7A/B, BAX, BBC3, CASP3/7/9, CDKN...…”

Potential of Polymeric Films Loaded with Gold Nanorods for Local Hyperthermia Applications

“…On the other hand, GnRs-loaded films showed a significant increase in temperature. To achieve local hyperthermia, and therefore a biological response of cell death or regeneration, heating cycles may be needed in order to maintain a temperature over 43 • C for a period of time [42,43]. Therefore, irradiation of polymeric films was conducted for 3 cycles of 10 s each, followed by cooling until room temperature, and thermal images were taken before and after this to calculate the increase in temperature.…”