STAT3, a transcription factor hyperactivated in various cancers, regulates critical processes like proliferation, apoptosis, chemoresistance, migration and invasion, epithelial-mesenchymal transition, and maintenance of cancer stem cells (CSCs). In this study, we identify (-)-α-Bisabolol, a natural sesquiterpene alcohol extracted from Matricaria Chamomilla’s oil, as a potential inhibitor of the STAT3 signalling cascade. The effect of (-)-α-bisabolol is evaluated in human triple-negative breast cancer cells (MDA-MB-231) and in patient-derived breast cancer stem cells (BCSCs) after exposure to sublethal doses of chemotherapeutic agents. Since STAT3 hyperactivation is implicated in multiple oncogenic pathways, the effects of (-)-α-bisabolol on proliferation, migration, and invasion are explored in both 2D and 3D cultures derived from MDA-MB-231 and BCSC1 cells. Our results show that: (1) (-)-α-bisabolol promotes apoptosis, and limits migration and invasion in 2D cultures; (2) (-)-α-bisabolol induces cytotoxic effect, decreases spheroid size, and downregulates EMT-related genes in 3D cultures. It is important to note that (-)-α-bisabolol has no effects on MCF10A, a pre-neoplastic mammary epithelial cell line. To overcome the limitations associated with the lipophilicity of (–)-α-bisabolol, we developed poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (α-bis-NPs) to improve its solubility and biological distribution. α-Bis-NPs are characterized for their chemical and physical properties, and treatment of cells with these nanoparticles resulted in enhanced effects compared to the free compound. Notably, the nanoparticle formulation produces stronger effects than the free compound when used to treat the cells. Our data suggest that (-)-α-bisabolol, particularly through nanoparticle delivery, as a promising strategy to target STAT3-dependent oncogenic features in triple-negative breast cancer and breast cancer stem cells.
α −Bisabolol Against Recurrence, Metastasis and Tumour Self-renewal in Triple Negative Breast Cancer
Mosaico
2026-01-01
Abstract
STAT3, a transcription factor hyperactivated in various cancers, regulates critical processes like proliferation, apoptosis, chemoresistance, migration and invasion, epithelial-mesenchymal transition, and maintenance of cancer stem cells (CSCs). In this study, we identify (-)-α-Bisabolol, a natural sesquiterpene alcohol extracted from Matricaria Chamomilla’s oil, as a potential inhibitor of the STAT3 signalling cascade. The effect of (-)-α-bisabolol is evaluated in human triple-negative breast cancer cells (MDA-MB-231) and in patient-derived breast cancer stem cells (BCSCs) after exposure to sublethal doses of chemotherapeutic agents. Since STAT3 hyperactivation is implicated in multiple oncogenic pathways, the effects of (-)-α-bisabolol on proliferation, migration, and invasion are explored in both 2D and 3D cultures derived from MDA-MB-231 and BCSC1 cells. Our results show that: (1) (-)-α-bisabolol promotes apoptosis, and limits migration and invasion in 2D cultures; (2) (-)-α-bisabolol induces cytotoxic effect, decreases spheroid size, and downregulates EMT-related genes in 3D cultures. It is important to note that (-)-α-bisabolol has no effects on MCF10A, a pre-neoplastic mammary epithelial cell line. To overcome the limitations associated with the lipophilicity of (–)-α-bisabolol, we developed poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (α-bis-NPs) to improve its solubility and biological distribution. α-Bis-NPs are characterized for their chemical and physical properties, and treatment of cells with these nanoparticles resulted in enhanced effects compared to the free compound. Notably, the nanoparticle formulation produces stronger effects than the free compound when used to treat the cells. Our data suggest that (-)-α-bisabolol, particularly through nanoparticle delivery, as a promising strategy to target STAT3-dependent oncogenic features in triple-negative breast cancer and breast cancer stem cells.
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