Levistolide A induces endoplasmic reticulum stress-triggered apoptosis via ATF6 in triple-negative breast cancer

Levistolide A(LA), a bioactive constituent extracted from the herbal plant Ligusticum chuanxiong possesses anticancer properties. Nevertheless, its functions and underlying processes in triple-negative breast cancer (TNBC) are not well defined.

We evaluated how LA affects endoplasmic reticulum (ER) stress in TNBC cells by dosing in vitro models with different concentrations. Cellular viability and proliferation were evaluated through CCK-8 assays, colony formation assays, and immunofluorescence microscopy. Following this, tumor cells were pre-incubated with the ER stress inhibitor melatonin, and alterations in apoptosis were quantified by flow cytometry. Expression patterns of ER stress-associated markers were analyzed at both protein and transcript levels using Western blotting and quantitative reverse transcription PCR. These in vitro observations were further corroborated in tumor xenograft models via immunohistochemical staining and hematoxylin-eosin (HE) staining, thereby confirming the contribution of ER stress to LA's antitumor activity.

Experimental findings revealed that LA markedly suppresses the proliferation of TNBC cells, triggers ER stress, and promotes cellular apoptosis. Conversely, when melatonin was administered to block ER stress, the ability of LA to both inhibit proliferation and stimulate apoptosis in TNBC cells was markedly restored.

Our findings indicate that LA inhibits TNBC progression by activating ER stress. This discovery suggests promising directions for developing innovative therapeutic interventions against TNBC in clinical practice.