Tanshinlactone triggers methuosis in breast cancer cells via NRF2 activation

Frontiers in Pharmacology, Год журнала: 2025, Номер 15

Опубликована: Янв. 21, 2025

Background Tanshinlactone is a compound derived from the herb Salvia miltiorrhiza . Breast cancer most prevalent malignancy among women globally. While significant strides have been made in breast management, these interventions are often impeded by substantial adverse effects that undermine patients’ quality of life and confront limitations due to eventual development multi-drug resistance. Catastrophic macropinocytosis, also called methuosis, as nonapoptotic cell death associated with cytoplasmic vacuolization, has gained increasing attention, largely because its potential importance therapy. Methods The effect tanshinlactone on growth human cells was evaluated using sulforhodamine B colony formation assay. Fluorescent dyes used label macropinosomes lysosomes. Phase contrast, confocal transmission electron microscopy were employed observe morphological changes. RT-PCR, western blot, lentiviral-mediated gene overexpression, pharmacological inhibitor assays comprehensively designed regulate identified signaling pathways confirm mechanism tanshinlactone. Human lines-derived xenograft tumor explants assay evaluate compound’s efficacy assess induction methuosis via NRF2 activation Results selectively inhibits ER+ HER2+/EGFR + while showing limited cytotoxicity against other types normal cells. selective anti-breast activity characterized vacuolization dysfunctional macropinocytosis. This process mediated transcription factor NRF2, leading fail fuse lysosomes or recycle plasma membrane, resulting death. vitro replicated murine model. Additionally, demonstrated effectiveness lapatinib-resistant cells, suggesting therapeutic agent for overcoming drug resistance treatment. Conclusion novel agent, capable inhibiting tumors through unique inducing catastrophic regimen holds promise targeted therapy minimized side offers new avenue patients drug-resistant diseases.

Язык: Английский

3-methyladenine ameliorates acute lung injury by inhibiting oxidative damage and apoptosis

Heliyon, Год журнала: 2024, Номер 10(13), С. e33996 - e33996

Опубликована: Июль 1, 2024

Acute lung injury (ALI) is a condition characterized by inflammation and oxidative damage. 3-methyladenine (3-MA) has great potential for regulating apoptosis, but its regulatory role in ALI unknown.

Язык: Английский

State‐of‐the‐art Nrf2 Inhibitors: Therapeutic Opportunities in Non‐cancer Diseases

ChemMedChem, Год журнала: 2024, Номер unknown

Опубликована: Июль 31, 2024

Abstract Nuclear factor erythroid 2‐related (Nrf2) is a cytoprotective transcription that induces the of genes responsible for cell's response to oxidative stress. While Nrf2 activation has led development clinically relevant therapeutics, oncogenic role in proliferation cancer cells underscored complex nature and necessity inhibitors. Although application inhibitors appears limited as anticancer agents, recent studies have begun pinpoint impairment autophagy diseases cellular marker shifts from protective deleterious state. Therefore, cytoplasmic accumulation can lead lipid hydroperoxides and, ultimately, ferroptosis. However, some aimed at elucidating non‐cancer yielded conflicting results, attributed differences approaches used inhibit or activate Nrf2, well variations vitro and/or vivo disease models. Overall, these results highlight deeper evaluation Nrf2′s diseases, especially chronic diseases. In this review, we discuss where inhibition holds potential beneficial therapeutic effects summarize recently reported exploiting medicinal chemistry suitable targeting factors like Nrf2.

Язык: Английский