RT Journal Article
T1 Inhibition of telomerase activity preferentially targets aldehyde dehydrogenase-positive cancer stem-like cells in lung cancer
A1 Serrano, Diego
A1 Bleau, Anne-Marie
A1 Fernandez-Garcia, Ignacio
A1 Fernández Marcelo, Tamara
A1 Iniesta Serrano, María Pilar
A1 Ortiz-de-Solorzano, Carlos
A1 Calvo, Alfonso
AB Background          Mortality rates for advanced lung cancer have not declined for decades, even with the implementation of novel chemotherapeutic regimens or the use of tyrosine kinase inhibitors. Cancer Stem Cells (CSCs) are thought to be responsible for resistance to chemo/radiotherapy. Therefore, targeting CSCs with novel compounds may be an effective approach to reduce lung tumor growth and metastasis. We have isolated and characterized CSCs from non-small cell lung cancer (NSCLC) cell lines and measured their telomerase activity, telomere length, and sensitivity to the novel telomerase inhibitor MST312.                   Results            The aldehyde dehydrogenase (ALDH) positive lung cancer cell fraction is enriched in markers of stemness and endowed with stem cell properties. ALDH+ CSCs display longer telomeres than the non-CSC population. Interestingly, MST312 has a strong antiproliferative effect on lung CSCs and induces p21, p27 and apoptosis in the whole tumor population. MST312 acts through activation of the ATM/pH2AX DNA damage pathway (short-term effect) and through decrease in telomere length (long-term effect). Administration of this telomerase inhibitor (40 mg/kg) in the H460 xenograft model results in significant tumor shrinkage (70% reduction, compared to controls). Combination therapy consisting of irradiation (10Gy) plus administration of MST312 did not improve the therapeutic efficacy of the telomerase inhibitor alone. Treatment with MST312 reduces significantly the number of ALDH+ CSCs and their telomeric length in vivo.              Conclusions            We conclude that antitelomeric therapy using MST312 mainly targets lung CSCs and may represent a novel approach for effective treatment of lung cancer.
PB BioMed Central
SN 1476-4598
YR 2011
FD 2011-08-09
LK https://hdl.handle.net/20.500.14352/114229
UL https://hdl.handle.net/20.500.14352/114229
LA eng
NO Serrano, D., Bleau, AM., Fernandez-Garcia, I. et al. Inhibition of telomerase activity preferentially targets aldehyde dehydrogenase-positive cancer stem-like cells in lung cancer. Mol Cancer 10, 96 (2011). https://doi.org/10.1186/1476-4598-10-96
NO Gobierno de Navarra Salud
NO Fundación de Investigación Médica Mutua Madrileña
NO Instituto de Salud Carlos III
NO Ministerio de Ciencia e Innovación (España)
DS Docta Complutense
RD 25 abr 2025