PO.MCB02.01 · 分子与细胞生物学
迷迭香酸抑制乳腺癌细胞增殖并诱导凋亡
Carnosic acid inhibits proliferation and induces apoptosis of breast cancer cells
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
乳腺癌仍是全球女性癌症相关死亡的主要原因之一，2022年造成估计约670,000例死亡。尽管早期检测和全身治疗的进步改善了预后，但发病率持续上升，且治疗耐药性——尤其是在三阴性乳腺癌(TNBC)等侵袭性亚型中——仍是一项关键挑战。植物来源的化学物质历来是抗癌药物的来源，紫杉醇的临床成功即为例证，凸显了植物来源化合物的持续潜力。在本研究中，我们考察了迷迭香酸(CA)——一种富含于迷迭香、鼠尾草和牛至中的多酚类二萜——在多种乳腺癌亚型中的抗癌作用。CA以剂量依赖方式显著抑制TNBC细胞系(MDA-MB-231、HCC70、HCC1143)和Luminal A细胞系(MCF7、T47D)的增殖，IC₅₀值在30至78 µM范围内(MDA-MB-231: 77.92 µM; HCC70: 63.51 µM; HCC1143: 38.56 µM; T47D: 30.29 µM)。CA诱导凋亡性细胞死亡，经MDA-MB-231、MCF7和T47D细胞中Annexin V/PI染色增加和切割型PARP水平升高所证实。此外，CA促进自噬，表现为LC3A/B-II积累增强和Beclin-1表达增加。CA的这些抗增殖和促凋亡作用与AMP活化蛋白激酶(AMPK)信号的强烈激活相关，表现为AMPK及其下游靶点乙酰辅酶A羧化酶(ACC)的磷酸化增加。综上，这些数据表明迷迭香酸抑制乳腺癌细胞增殖，诱导凋亡和自噬，并伴随AMPK激活。这些发现支持CA作为一种有前景的植物来源治疗候选物，并证明有必要在乳腺癌体内模型中进一步评估。
查看英文原文 English 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.
利益披露 Disclosure
A. L. Kornel, None.