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Repurposing existing drugs appears to be a potential solution for addressing the challenges in the treatment of non-small cell lung cancer (NSCLC). β-adrenoceptor antagonist drugs (β-blockers) have tumor-inhibiting effects, making them promising candidates for potential NSCLC treatment. This study investigates the anticancer potential of a subset of β-blockers in NSCLC cell lines; A549 and H1299. Additionally, it investigates the underlying mechanism behind β-blockers’ anticancer effect by influencing a potential novel target named aldehyde dehydrogenase (ALDH). The MTT assay assessed β-blockers’ cytotoxicity on both cell lines, while Western blot and NADH fluorescence assays evaluated their influence on ALDH protein expression and activity. Carvedilol (CAR) was the most effective blocker in reducing cell survival of A549 and H1299 with IC50 of 18 µM and 13.7 µM, respectively. Significantly, CAR led to a 50% reduction in ALDH expression and 80% decrease in ALDH activity in A549 cells, especially when combined with β-agonists, in comparison to the control. This effect might be attributed to β-agonist blockade or an alternative pathway. This novel finding adds to our understanding of CAR’s multifaceted anticancer properties, implying that combining CAR with β-agonists could be a useful strategy for lung cancer treatment.

Background/Objective/Methods: Capsaicin micelles were prepared by the direct dissolution using the amphiphilic copolymer Pluronic P123 and advanced for substantially novel submicro-nanocytotoxicity. Results: Superior cytotoxicity of capsaicin loaded nanomicelles vs. both the raw capsaicin and reference cisplatin in pancreatic PANC1, breast MCF7, colorectal resistant CACO2, skin A375, lung A549 and prostate PC3 cancer cell lines were delineated. Nicotinic acid (NA) derivative 39 (2-Amino IsoNA) had antiinflammatory potential but consistently lacked antiproliferation in MCF7, PANC1 and CACO2. Besides NA derivatives 8 (5-MethylNA) and 44 (6-AminoNA) exhibited lack of antiinflammation but had comparable antitumorigenesis potency to cisplatin in PANC1 cells. Though capsaicin loaded nanomicelles exerted pronounced antiinflammation (with IC50 value of 510 nM vs. Indomethacin's) in lipopolysacchride-induced inflammation of RAW247.6 macrophages; they lacked DPPH scavenging propensities. Free capsaicin proved more efficacious vs. its loaded nanocarriers to chemosensitize cytotoxicity of combinations with NAs 1(6-Hexyloxy Nicotinic Acid), 5(6-OctyloxyNA), 8(5-MethylNA), 12(6-Thien-2yl-NA), 13(5,6-DichloroNA) and 44(6-AminoNA) in CACO2, PANC1 and prostate PC3. Conclusion: Capsaicin loaded nanomicelles proved more efficacious vs. free capsaicin to chemo-sensitize antiproliferation of cotreatments with NA derivatives, 1, 5, 8, 12, 13 and 44 (in skin A375), 1, 5, 8 and 12 (in breast MCF7), and 1, 5, 12 and 44 (in lung A549).