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A novel aldehyde dehydrogenase-3 activator (Alda-89) protects submandibular gland function from irradiation without accelerating tumor growth
Clinical cancer research : an official journal of the American Association for Cancer Research
  • Nan (Tori) Xiao, University of the Pacific
  • Hongbin Cao
  • Che-Hong Chen
  • Christina S. Kong
  • Rehan Ali
  • Cato Chan
  • Davud Sirjani
  • Edward Graves
  • Albert Koong
  • Amato Giaccia
  • Daria Mochly-Rosen
  • Quynh-Thu Le
Document Type
Article
DOI
10.1158/1078-0432.CCR-13-0127
Publication Date
8-15-2013
Disciplines
Abstract

PURPOSE: To determine the effect of Alda-89 (an ALDH3 activitor) on (i) the function of irradiated (radiotherapy) submandibular gland (SMG) in mice, (ii) its toxicity profile, and (iii) its effect on the growth of head and neck cancer (HNC) in vitro and in vivo.

EXPERIMENTAL DESIGN: Adult mice were infused with Alda-89 or vehicle before, during, and after radiotherapy. Saliva secretion was monitored weekly. Hematology, metabolic profile, and postmortem evaluation for toxicity were examined at the time of sacrifice. Alda-89 or vehicle was applied to HNC cell lines in vitro, and severe combined immunodeficient (SCID) mice transplanted with HNC in vivo with or without radiation; HNC growth was monitored. The ALDH3A1 and ALDH3A2 protein expression was evaluated in 89 patients with HNC and correlated to freedom from relapse (FFR) and overall survival (OS).

RESULTS: Alda-89 infusion significantly resulted in more whole saliva production and a higher percentage of preserved acini after radiotherapy compared with vehicle control. There was no difference in the complete blood count, metabolic profile, and major organ morphology between the Alda-89 and vehicle groups. Compared with vehicle control, Alda-89 treatment neither accelerated HNC cell proliferation in vitro, nor did it affect tumor growth in vivo with or without radiotherapy. Higher expression of ALDH3A1 or ALDH3A2 was not significantly associated with worse FFR or OS in either human papillomavirus (HPV)-positive or HPV-negative group.

CONCLUSION: Alda-89 preserves salivary function after radiotherapy without affecting HNC growth or causing measurable toxicity in mice. It is a promising candidate to mitigate radiotherapy-related xerostomia.

Citation Information
Nan (Tori) Xiao, Hongbin Cao, Che-Hong Chen, Christina S. Kong, et al.. "A novel aldehyde dehydrogenase-3 activator (Alda-89) protects submandibular gland function from irradiation without accelerating tumor growth" Clinical cancer research : an official journal of the American Association for Cancer Research Vol. 19 Iss. 16 (2013) p. 4455 - 4464 ISSN: 1078-0432
Available at: http://works.bepress.com/nan-xiao/25/