Carnosic acid (CA) is a phenolic diterpene with many important biological activities including antimicrobial, antioxidant, anti-inflammatory properties, and anti-proliferative properties. The aim of the present study was to investigate cytotoxic activity, cell cycle, apoptotic, and molecular effects attributed to CA in non-tumoral IMR-90 (human fetal lung fibroblasts), as well as tumoral NCI-H460 (human non–small-cell lung cancer) cell lines. Cell proliferation was evaluated by Real-Time Cell Analysis system, while apoptosis and cell cycle were assessed using flow cytometry. RT-qPCR was used to estimate the relative expression of genes involved in cell cycle regulation, DNA damage and repair, and apoptosis induction. CA inhibited proliferation of IMR-90 and NCI-H460 cells via cell cycle arrest at G₀/G₁ and G₂/M phases, according to the treatment concentration. The mRNA levels of genes encoding cyclins A2, B1, and B2 were downregulated in response to CA treatment of IMR-90 cells. Apoptosis was induced and proapoptotic gene PUMA was upregulated in both cell lines. mRNA levels of genes ATR, CCND1, CHK1, CHK2, MYC, GADD45A, H2AFX, MTOR, TP53, and BCL2, CASP3 were not markedly changed following CA treatments. Although CA exerted antiproliferative activity against NCI-H460 tumor cells, this phytochemical induced toxic effects in non-tumoral cells, and thus needs to be considered carefully prior to pharmacological use therapeutically.

肌酸（CA）是一种酚二萜，具有许多重要的生物学活性，包括抗微生物，抗氧化剂，抗炎特性和抗增殖特性。本研究的目的是研究归因于非肿瘤IMR-90（人胎肺成纤维细胞）和肿瘤NCI-H460（人非小细胞癌）中CA的细胞毒活性，细胞周期，凋亡和分子效应。细胞肺癌）细胞系。通过实时细胞分析系统评估细胞增殖，而使用流式细胞术评估细胞凋亡和细胞周期。RT-qPCR被用于估计参与细胞周期调控，DNA损伤和修复以及细胞凋亡诱导的基因的相对表达。CA通过在G ₀ / G处阻滞细胞周期抑制IMR-90和NCI-H460细胞的增殖₁和G ₂ / M相，根据处理浓度而定。响应于CA处理IMR-90细胞，编码细胞周期蛋白A2，B1和B2的基因的mRNA水平下调。在两种细胞系中均诱导了凋亡，并且凋亡基因PUMA被上调。CA处理后，基因ATR，CCND1，CHK1，CHK2，MYC，GADD45A，H2AFX，MTOR，TP53和BCL2，CASP3的mRNA水平没有明显改变。尽管CA对NCI-H460肿瘤细胞具有抗增殖活性，但是这种植物化学作用在非肿瘤细胞中具有毒性作用，因此在进行药物治疗前需要仔细考虑。