Benzethonium chloride suppresses lung cancer tumorigenesis through inducing p38-mediated cyclin D1 degradation

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Lung cancer remains a leading cause of cancer mortality globally.
• Current therapeutic options for lung cancer have limitations.
• There is a critical need for novel and effective anticancer strategies.

Purpose of the Study:

• To identify novel anticancer agents from a Food and Drug Administration (FDA)-approved drug library.
• To evaluate the efficacy of Benzethonium Chloride (BZN) as a potential lung cancer therapeutic.
• To elucidate the underlying molecular mechanisms of BZN's anticancer effects.

Main Methods:

• Screening of a 528-compound FDA-approved drug library.
• In vitro assays assessing lung cancer cell proliferation, apoptosis, and colony formation.
• In vivo studies using tumor xenografts in nude mice.
• Quantitative proteomics, bioinformatics analysis, and functional assays to determine molecular mechanisms.

Main Results:

• Benzethonium Chloride (BZN) significantly inhibited lung cancer cell proliferation, induced apoptosis, and reduced colony formation in a dose- and time-dependent manner.
• BZN enhanced the sensitivity of lung cancer cells to gefitinib, a first-line treatment.
• In vivo, BZN significantly delayed tumor xenograft growth by increasing apoptosis and decreasing proliferation, with no obvious toxic effects.
• Mechanistically, BZN induced G1 cell cycle arrest via p38-mediated phosphorylation and cyclin D1 degradation.

Conclusions:

• Benzethonium Chloride (BZN) demonstrates significant anticancer activity against lung cancer cells in vitro and in vivo.
• BZN exhibits a promising therapeutic potential as a novel agent for lung cancer treatment, potentially in combination with gefitinib.
• The study elucidates BZN's mechanism involving cell cycle arrest and modulation of key regulatory proteins.