Abstract 4655: Carnosic acid inhibits proliferation and induces apoptosis of breast cancer cells

Abstract Breast cancer remains a major cause of cancer-related mortality among women worldwide, contributing to an estimated 670,000 deaths in 2022. Although advances in early detection and systemic therapy have improved outcomes, incidence rates continue to rise, and therapeutic resistance—particularly in aggressive subtypes such as triple-negative breast cancer (TNBC)—remains a critical challenge. Plant-derived chemicals have historically served as a source of anticancer agents, exemplified by the clinical success of paclitaxel, highlighting the continued potential of plant-derived compounds.In this study, we examined the anticancer effects of carnosic acid (CA), a polyphenolic diterpene abundant in rosemary, sage, and oregano, across multiple breast cancer subtypes. CA significantly suppressed proliferation of TNBC cell lines (MDA-MB-231, HCC70, HCC1143) and Luminal A cell lines (MCF7, T47D) in a dose-dependent manner with IC50 values in the range of 30 to 78 μM, (MDA-MB-231: 77.92 μM; HCC70: 63.51μM; HCC1143: 38.56 μM; T47D: 30.29μM).CA induced apoptotic cell death, confirmed by increased Annexin V/PI staining and elevated levels of cleaved PARP in MDA-MB-231, MCF7, and T47D cells. Additionally, CA promoted autophagy, demonstrated by enhanced LC3A/B-II accumulation and increased Beclin-1 expression.These anti-proliferative and pro-apoptotic effects of CA were associated with robust activation of AMP-activated protein kinase (AMPK) signaling, as evidenced by increased phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase (ACC).Collectively, these data indicate that carnosic acid suppresses breast cancer cell proliferation, induces apoptosis and autophagy with a concomitant AMPK activation. These findings support CA as a promising plant-derived therapeutic candidate and justify further evaluation in in vivo breast cancer models. Citation Format: Amanda L. Kornel, Evangelia Tsiani. Carnosic acid inhibits proliferation and induces apoptosis of breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4655.