Research Paper Volume 15, Issue 15 pp 7496—7512

Study on the effect of a triple cancer treatment of propolis, thermal cycling-hyperthermia, and low-intensity ultrasound on PANC-1 cells

Yu-Yi Kuo1,2, , Wei-Ting Chen1,2, , Guan-Bo Lin1,2, , Chueh-Hsuan Lu1,2, , Chih-Yu Chao1,2,3, ,

  • 1 Department of Physics, Lab for Medical Physics and Biomedical Engineering, National Taiwan University, Taipei, Taiwan
  • 2 Molecular Imaging Center, National Taiwan University, Taipei, Taiwan
  • 3 Graduate Institute of Applied Physics, Biophysics Division, National Taiwan University, Taipei, Taiwan

Received: February 10, 2023       Accepted: July 6, 2023       Published: July 27, 2023
How to Cite

Copyright: © 2023 Kuo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


To reduce side effects and enhance treatment efficacy, study on combination therapy for pancreatic cancer, a deadly cancer, has gained much attraction in recent years. In this study, we propose a novel triple treatment combining propolis and two physical stimuli-thermal cycling-hyperthermia (TC-HT) and low-intensity ultrasound (US). The study found that, after the triple treatment, the cell viability of a human cancer cell line PANC-1 decreased to a level 80% less than the control, without affecting the normal pancreatic cells. Another result was excessive accumulation of reactive oxygen species (ROS) after the triple treatment, leading to the amplification of apoptotic pathway through the MAPK family and mitochondrial dysfunction. This study, to the best of our knowledge, is the first attempt to combine TC-HT, US, and a natural compound in cancer treatment. The combination of TC-HT and US also promotes the anticancer effect of the heat-sensitive chemotherapy drug cisplatin on PANC-1 cells. It is expected that optimized parameters for different agents and different types of cancer will expand the methodology on oncological therapy in a safe manner.


ANOVA: analysis of variance; DHE: dihydroethidium; DiOC6(3): 3,3′-dihexyloxacarbocyanine iodide; ECL: enhanced chemiluminescence; FBS: fetal bovine serum; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HCl: hydrochloric acid; HIFU: high-intensity focused ultrasound; MAPK: mitogen-activated protein kinase; MMP: mitochondrial membrane potential; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NAC: N-acetyl-cysteine; O2‧−: superoxide radical anion; p-ERK: phosphorylated extracellular signal-regulated kinases; p-JNK: phosphorylated c-Jun N-terminal kinase; p-p38: phosphorylated p38 MAPK; PARP: poly (ADP-ribose) polymerase; PBS: phosphate buffered saline; PCR: polymerase chain reaction; PI: propidium iodide; PVDF: polyvinylidene fluoride; ROS: reactive oxygen species; SDS: sodium dodecyl sulfate; SDS-PAGE: SDS-polyacrylamide gel electrophoresis; TC-HT: thermal cycling-hyperthermia; US: ultrasound.