Institute of Biochemistry and Biophysics, Department of Biochemistry, University of Tehran, Tehran, Iran.
Institute of Biotechnology, Shiraz University, Shiraz, Iran.
Sci Rep. 2017 May 31;7(1):2553. doi: 10.1038/s41598-017-02633-z.
Recognizing new anticancer compounds to improve Breast cancer treatment seems crucial. Essential oil of Zataria Multiflora (ZEO) is a secondary metabolite with some biological properties, yet underlying cellular and molecular anticancer properties of ZEO is unclear. GC/MS analysis revealed that carvacrol is the major ingredient of the essential oil. ZEO increasingly suppressed viability in MDA-MB-231, MCF-7 and T47D Breast cancer cells while nontoxic to L929 normal cells in monolayer cell cultures (2D), whereas MDA-MB-231 multicellular spheroids (3D) were more resistant to inhibition. ZEO significantly induced cell apoptosis confirmed by fluorescent staining, flow cytometry analysis and DNA fragmentation in MDA-MB-231 2D and 3D cell cultures. ZEO increased ROS generation and subsequent loss of ΔΨm, caspase 3 activation and DNA damage which consequently caused G1 and G2/M cell cycle arrest in a dose- and time-dependent manner in 2D. S phase arrest occurred in cell spheroids therefore ZEO possible DNA interaction with gDNA was investigated and revealed ZEO binds DNA via intercalation. Altogether, these data corroborate anticancer properties of ZEO and suggest that cell culture format (2D monolayer vs. 3D spheroid) plays a critical role in drug response and provides new insights into the mechanisms underlying ZEO cytotoxicity effect on Breast cancer cells.
识别新的抗癌化合物以改善乳腺癌治疗似乎至关重要。香薷精油（ZEO）是一种具有某些生物特性的次生代谢物，但 ZEO 的潜在细胞和分子抗癌特性尚不清楚。GC/MS 分析显示，香芹酚是精油的主要成分。ZEO 在单层细胞培养物（2D）中逐渐抑制 MDA-MB-231、MCF-7 和 T47D 乳腺癌细胞的活力，而对 L929 正常细胞无毒，而 MDA-MB-231 多细胞球体（3D）则对抑制更具抵抗力。荧光染色、流式细胞术分析和 MDA-MB-231 2D 和 3D 细胞培养物中的 DNA 片段证实，ZEO 显著诱导细胞凋亡。ZEO 增加 ROS 生成，随后导致 ΔΨm 丧失、caspase 3 激活和 DNA 损伤，从而导致 2D 中细胞周期在剂量和时间依赖性方式下 G1 和 G2/M 期停滞。细胞球体中发生 S 期停滞，因此研究了 ZEO 与 gDNA 的可能相互作用，结果表明 ZEO 通过嵌入与 DNA 结合。总之，这些数据证实了 ZEO 的抗癌特性，并表明细胞培养形式（2D 单层与 3D 球体）在药物反应中起着关键作用，并为 ZEO 对乳腺癌细胞细胞毒性作用的机制提供了新的见解。
