75P - Inhibition and exploitation of aldehyde dehydrogenase 1 (ALDH1) as a cancer stem cell marker in cisplatin resistant NSCLC

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Anticancer Agents
Thoracic Malignancies
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Biological Therapy
Presenter Martin Barr
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors M.P. Barr1, L. Mac Donagh1, S.G. Gray1, K. O'Byrne2, S. Cuffe1, S. Finn3
  • 1Thoracic Oncology, St James's Hospital, D8 - Dublin/IE
  • 2Cancer & Ageing Research Program, Queensland University of Technology, 4102 - Brisbane/AU
  • 3Histopathology, St James's Hospital, D8 - Dublin/IE



The root of therapeutic resistance is hypothesized to be due to the presence of a rare CSC population within the tumour population. When challenged with chemotherapy, this tumour cell subset survives the insult and has the potential to recapitulate a heterogenic tumour. Aldehyde dehydrogenase 1 (ALDH1) is involved in the catalytic conversion of vitamin A (retinol) to retinoic acid and has been identified as a CSC marker in a number of solid malignancies.


FACS analysis of an isogenic panel of matched parent (PT) and cisplatin resistant (CisR) NSCLC cell lines of different histologies was used to examine ALDH1 activity. The H460 CisR subline was FACS-sorted (MoFlo®) into ALDH1-positive and ALDH1-negative fractions and subcutaneously injected into NOD/SCID mice to assess tumour initiation and growth. The effects of inhibiting ALDH1 on cell proliferation (BrdU), apoptosis (Annexin-V/propidium iodide) and colony formation (crystal violet) in PT and CisR cell lines was assessed in vitro using two ALDH1 inhibitors, DEAB (N,N-diethylaminobenzaldehyde) and disulfiram (Antabuse), alone and in combination with cisplatin. Lung cancer cells were treated with retinol and All-trans retinoic acid (ATRA) to exploit the role of ALDH1 in the vitamin A/retinoic acid axis in NSCLC.


ALDH1 activity was significantly increased in all CisR cell lines relative to their parental counterparts in which little or no ALDH1 expression was detected. Xenograft studies using ALDH1+ and ALDH1 fractions from H460 CisR cells showed no significant difference in tumour growth in mice. ALDH1 inhibition, in combination with cisplatin, significantly decreased cell viability, proliferation and clonogenic survival of CisR sublines only and increased apoptotic cell death compared to cells treated with cisplatin alone. Similarly, treatment of cells with retinol or ATRA, in combination with cisplatin, showed similar re-sensitizing effects.


In this study, we show that inhibition of the CSC marker, ALDH1, re-sensitizes cisplatin resistant NSCLC cells to the cytotoxic effects of cisplatin. Furthermore, our data suggest a role for ALDH1 as a key enzyme in the vitamin A/retinoic acid axis.

Clinical trial identification

Legal entity responsible for the study

Trinity College Dublin


Molecular Medicine Ireland Clinical & Translational Research Scholars Programme


All authors have declared no conflicts of interest.