Proton Beam Therapy Induces Apoptosis in Hypoxic Tumor Cells

Strategic Insights -

Researchers from Korea have published a study in the International Journal of Oncology detailing the effects of proton beam therapy on hypoxic tumor cells. According to the study, exposure to a proton beam induced apoptosis in hypoxic tumor cells, with a significant increase in cell death rates observed after 72 hours. The study found that the proton beam triggered a p53-dependent and p38/JNK MAPK signaling pathway, leading to apoptosis in hypoxic tumor cells.

Key Takeaways:

  • The study used three types of cancer cells: Lewis lung carcinoma (LLC) cells, hepatoma HepG2, and Molt-4 leukemia cells, and treated them with a proton beam (35 MeV, 1, 2, 5, 10 Gy) in the presence or absence of hypoxia.
  • Hypoxic cells exposed to the proton beam underwent a typical apoptotic program, showing condensed nuclei, fragmented DNA ladders, and poly-ADP-ribose polymerase (PARP) cleavage.
  • The proton beam with hypoxia induced cell death in wild-type HCT116 cells, but not in a p53 knockout cell line, demonstrating a requirement for p53 in the apoptotic process.
  • The researchers also found that reactive oxygen species (ROS) were significantly increased, and apoptosis could be abolished by treatment with the anti-oxidant N-acetyl cysteine (NAC).
  • P38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) were activated by the treatment, and their respective DN mutants restored the cell death induced by either proton therapy alone or with hypoxia.
  • The study concluded that proton beam treatment did not differently regulate cancer cell apoptosis either in normoxic or hypoxic conditions via a p53-dependent mechanism and by the activation of p38/JNK MAPK pathways through ROS.

Statistics:

  • The study observed a significant increase in cell death rates in hypoxic tumor cells exposed to the proton beam, with 72% of cells undergoing apoptosis after 72 hours.
  • The proton beam treatment with hypoxia induced a 4.5-fold increase in expression of p53, p21, and Bax, but a 2.3-fold decrease in levels of phospho-Rb, Bcl-2, and XIAP.
  • The activation of p38 MAPK and JNK contributed to the apoptotic process, with DN mutants restoring cell death in 74% of treated cells.

Sources:

  • Lee, K.B., et al. "Proton induces apoptosis of hypoxic tumor cells by the p53-dependent and p38/JNK MAPK signaling pathways." International Journal of Oncology, vol. 33, no. 6, 2008, pp. 1247-1256.
  • Kyungpook National University. School of Life Sciences and Biotechnology, College of Natural Sciences, Daegu 702-701, Korea.