Hyperoside exhibits anticancer activity in non‑small cell lung cancer cells with T790M mutations by upregulating...

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Acquired epidermal growth factor receptor (EGFR) T790M mutations are a primary cause of resistance to EGFR-tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC).
• The limitations of current treatments, including high costs and acquired resistance, necessitate the exploration of alternative therapeutic strategies for T790M-positive NSCLC.
• Hyperoside, a natural compound from Hypericum perforatum, has demonstrated anticancer properties in various tumor models.

Purpose of the Study:

• To investigate the efficacy of hyperoside in treating NSCLC harboring T790M mutations.
• To elucidate the molecular mechanisms underlying hyperoside's anticancer effects in this specific context.

Main Methods:

• In vitro assays including cell viability and apoptosis analysis were conducted.
• Molecular mechanisms were explored using reverse transcription-quantitative PCR and western blot analysis.
• In vivo efficacy was assessed through animal experiments and immunohistochemistry on NSCLC xenografts.

Main Results:

• Hyperoside significantly inhibited the proliferation and induced apoptosis in T790M-positive NSCLC cells.
• Hyperoside treatment led to the upregulation of forkhead box protein O1 (FoxO1) and downregulation of long non-coding RNA colon cancer associated transcript 1 (CCAT1).
• In vivo studies confirmed that hyperoside suppressed the growth of T790M-positive NSCLC xenografts.

Conclusions:

• Hyperoside demonstrates significant anticancer activity against T790M-positive NSCLC by modulating the FoxO1 and CCAT1 pathways.
• The findings suggest that hyperoside warrants further investigation as a novel therapeutic candidate for T790M-positive NSCLC.
• Hyperoside's mechanism involves upregulating FoxO1 expression, potentially mediated by the downregulation of CCAT1, leading to reduced proliferation and enhanced apoptosis.