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Title: The natural-based antitumor compound T21 decreases survivin levels through potent STAT3 inhibition in lung cancer models
Author: Martínez García, David
Pérez-Hernández, Marta
Korrodi-Gregório, Luís
Quesada, Roberto
Ramos Izquierdo, Ricard
Baixeras, Núria
Pérez Tomás, Ricardo E.
Soto Cerrato, Vanessa
Keywords: Tractament adjuvant del càncer
Càncer de pulmó
Adjuvant treatment of cancer
Lung cancer
Issue Date: 13-Aug-2019
Abstract: Lung cancer is the leading cause of cancer-related deaths worldwide; hence novel treatments for this malignancy are eagerly needed. Since natural-based compounds represent a rich source of novel chemical entities in drug discovery, we have focused our attention on tambjamines, natural compounds isolated from marine invertebrates that have shown diverse pharmacological activities. Based on these structures, we have recently identified the novel indole-based tambjamine analog 21 (T21) as a promising antitumor agent, which modulates the expression of apoptotic proteins such as survivin. This antiapoptotic protein plays an important role in carcinogenesis and chemoresistance. In this work, we have elucidated the molecular mechanism by which the anticancer compound T21 exerts survivin inhibition and have validated this protein as a therapeutic target in di erent lung cancer models. T21 was able to reduce survivin protein levels in vitro by repressing its gene expression through the blockade of Janus kinase/Signal Transducer and Activator of Transcription-3 (JAK/STAT3)/survivin signaling pathway. Interestingly, this occurred even when the pathway was overstimulated with its ligand interleukin 6 (IL-6), which is frequently overexpressed in lung cancer patients who show poor clinical outcomes. Altogether, these results show T21 as a potent anticancer compound that e ectively decreases survivin levels through STAT3 inhibition in lung cancer, appearing as a promising therapeutic drug for cancer treatment.
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It is part of: Biomolecules, 2019, vol. 9, num. 8, p. 361
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ISSN: 2218-273X
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Patologia i Terapèutica Experimental)

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