ArticleMolecular cancer therapeutics2013
A novel sulindac derivative inhibits lung adenocarcinoma cell growth through suppression of Akt/mTOR signaling and induction of autophagy.
Article in Molecular cancer therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 39 citations in OpenAlex.
- ADT-030, a novel PDE10 inhibitor, demonstrates potent antitumor activity in pancreatic ductal adenocarcinoma.bioRxiv : the preprint server for biology · 2026Article
- Unlocking the dual role of autophagy: A new strategy for treating lung cancer.Journal of pharmaceutical analysis · 2025Review
- Sulindac exhibits anti-proliferative and anti-invasive effects and enhances the sensitivity to paclitaxel in ovarian cancer.Frontiers in pharmacology · 2025Article
- Review
- KRIT1: A Traffic Warden at the Busy Crossroads Between Redox Signaling and the Pathogenesis of Cerebral Cavernous Malformation Disease.Antioxidants & redox signaling · 2023Review
- Article
- Phosphodiesterase 10A (PDE10A) as a novel target to suppress β-catenin and RAS signaling in epithelial ovarian cancer.Journal of ovarian research · 2022Article
- YAP manipulates proliferation via PTEN/AKT/mTOR-mediated autophagy in lung adenocarcinomas.Cancer cell international · 2021Article
- Diclofenac impairs autophagic flux via oxidative stress and lysosomal dysfunction: Implications for hepatotoxicity.Redox biology · 2020Article
- Development and validation of a survival model for lung adenocarcinoma based on autophagy-associated genes.Journal of translational medicine · 2020Article
- Tuning isoform selectivity and bortezomib sensitivity with a new class of alkenyl indene PDI inhibitor.European journal of medicinal chemistry · 2020Article
- Regulation of Autophagy by Non-Steroidal Anti-Inflammatory Drugs in Cancer.Cancer management and research · 2020Review
- Pivotal role of mitophagy in response of acute myelogenous leukemia to a ceramide-tamoxifen-containing drug regimen.Experimental cell research · 2019Article
- Oxazole and thiazole analogs of sulindac for cancer prevention.Future medicinal chemistry · 2018Article
- Partial Bile Duct Ligation in the Mouse: A Controlled Model of Localized Obstructive Cholestasis.Journal of visualized experiments : JoVE · 2018Article
- A novel multikinase inhibitor R8 exhibits potent inhibition on cancer cells through both apoptosis and autophagic cell death.Oncotarget · 2017Article
- The mTOR inhibition in concurrence with ERK1/2 activation is involved in excessive autophagy induced by glycyrrhizin in hepatocellular carcinoma.Cancer medicine · 2017Article
- Spermidine Prolongs Lifespan and Prevents Liver Fibrosis and Hepatocellular Carcinoma by Activating MAP1S-Mediated Autophagy.Cancer research · 2017Article
- Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: Two sides of the same coin.The international journal of biochemistry & cell biology · 2016Review
- Endoplasmic reticulum-Golgi intermediate compartment protein 3 knockdown suppresses lung cancer through endoplasmic reticulum stress-induced autophagy.Oncotarget · 2016Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Nonsteroidal anti-inflammatory drugs such as sulindac sulfide have shown promising antineoplastic activity in multiple tumor types, but toxicities resulting from COX inhibition limit their use in cancer therapy. We recently described a N,N-dimethylethyl amine derivative of sulindac sulfide, sulindac sulfide amide (SSA), that does not inhibit COX-1 or -2, yet displays potent tumor cell growth-inhibitory activity. Here, we studied the basis for the growth-inhibitory effects of SSA on human lung adenocarcinoma cell lines. SSA potently inhibited the growth of lung tumor cells with IC50 values of 2 to 5 μmol/L compared with 44 to 52 μmol/L for sulindac sulfide. SSA also suppressed DNA synthesis and caused a G0-G1 cell-cycle arrest. SSA-induced cell death was associated with characteristics of autophagy, but significant caspase activation or PARP cleavage was not observed after treatment at its IC50 value. siRNA knockdown of Atg7 attenuated SSA-induced autophagy and cell death, whereas pan-caspase inhibitor ZVAD was not able to rescue viability. SSA treatment also inhibited Akt/mTOR signaling and the expression of downstream proteins that are regulated by this pathway. Overexpression of a constitutively active form of Akt was able to reduce autophagy markers and confer resistance to SSA-induced cell death. Our findings provide evidence that SSA inhibits lung tumor cell growth by a mechanism involving autophagy induction through the suppression of Akt/mTOR signaling. This unique mechanism of action, along with its increased potency and lack of COX inhibition, supports the development of SSA or related analogs for the prevention and/or treatment of lung cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.