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Sertaconazole provokes proapoptotic autophagy via stabilizing TRADD in nonsmall cell lung cancer cells

Wenhui Zhang1, Li Zhou2, Siyuan Qin2

  • 1Department of Medical Oncology The Second Affiliated Hospital of Kunming Medical University Kunming P.R. China.

Medcomm
|January 3, 2022
PubMed

Insights

The antifungal drug sertaconazole shows potent anti-nonsmall cell lung cancer (NSCLC) effects by inducing apoptosis and autophagy. It stabilizes TRADD, a protein crucial for triggering this cell death pathway, offering a new therapeutic avenue for NSCLC.

Area of Science:

  • Oncology
  • Pharmacology
  • Cell Biology

Background:

  • Nonsmall cell lung cancer (NSCLC) presents significant challenges due to low cure rates and poor survival.
  • Existing treatments for NSCLC often face limitations in efficacy and consistency.
  • There is a critical need for novel therapeutic strategies to improve outcomes for NSCLC patients.

Purpose of the Study:

  • To investigate the potential of the antifungal agent sertaconazole as a treatment for nonsmall cell lung cancer.
  • To elucidate the molecular mechanisms underlying sertaconazole's anti-NSCLC activity, focusing on apoptosis and autophagy.
  • To evaluate the role of TNF receptor type 1 associated death domain protein (TRADD) in sertaconazole-mediated cancer cell death.

Main Methods:

  • In vitro and in vivo experiments were conducted to assess the efficacy of sertaconazole against NSCLC.
  • Autophagic flux and apoptosis induction were analyzed following sertaconazole treatment.
  • The expression and stability of TRADD protein were examined, along with its impact on Akt phosphorylation and downstream signaling pathways.

Main Results:

  • Sertaconazole demonstrated potent inhibition of NSCLC cell growth both in vitro and in vivo.
  • The drug effectively induced complete autophagic flux and promoted apoptosis in NSCLC cells.
  • Sertaconazole stabilized TRADD by preventing its ubiquitination, leading to Akt dephosphorylation and triggering proapoptotic autophagy.

Conclusions:

  • Sertaconazole exhibits significant potential as an anti-NSCLC therapeutic agent.
  • Its mechanism involves stabilizing TRADD, which initiates proapoptotic autophagy and suppresses tumor growth.
  • These findings suggest sertaconazole as a promising new treatment option for patients with nonsmall cell lung cancer.
Keywords:
NSCLCTRADDapoptosisautophagysertaconazole

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