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

Angel Resendez, Dhanir Tailor, Edward Graves, Sanjay V. Malhotra

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 in vitro 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 in vitro 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.

Original languageEnglish (US)
Pages (from-to)1314-1321
Number of pages8
JournalACS Medicinal Chemistry Letters
Volume10
Issue number9
DOIs
StatePublished - Sep 12 2019
Externally publishedYes

Keywords

  • 4-azapodophyllotoxin
  • Radiosensitizer
  • combination therapy
  • head and neck squamous cell carcinoma

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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