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ACS medicinal chemistry letters
Sep 12, 2019;10 (9): 1314-1321.

Radiosensitization of Head and Neck Squamous Cell Carcinoma (HNSCC) by a Podophyllotoxin.

Angel Resendez, Dhanir Tailor, Edward Graves, Sanjay V Malhotra
Author Information
  1. Angel Resendez: Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, California 94304, United States.
  2. Dhanir Tailor: Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, California 94304, United States.
  3. Edward Graves: Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, California 94304, United States.
  4. Sanjay V Malhotra: Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, California 94304, United States.
PMID: 31531203 DOI: 10.1021/acsmedchemlett.9b00270

Abstract

Surgical resection and radiotherapy are an effective treatment in many head and neck squamous cell carcinomas (HNSCC), but in others, the development of radiotherapy resistance limits treatment efficacy and permits disease progression. We developed a novel multiwell radiation dosing method to increase the throughput of our investigation of the activity of a novel podophyllotoxin SU093 in acting as a radiosensitizer in the HNSCC models FaDu and SCC-25. These studies showed that combining SU093 with 5 Grays ionizing radiation acted synergistically to increase HNSCC apoptosis and decrease its proliferation via inhibition of Nuclear factor, erythroid 2 like 2 (Nrf2), a key effector of the DNA damage response induced by ionizing radiation. Combined treatment reduced migration in a simulated wounding model while also promoting cell cycle arrest at the G2/M phase. These findings validate the potential of SU093 as a synergistic radiosensitizing agent for use in combination with localized radiotherapy in treatment resistant HNSCC.

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Grants

  1. T32 CA121940/NCI NIH HHS
Journal Article

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