Bidooki Seyed Hesamoddin, Quero Javier, Sánchez-Marco Javier, Herrero-Continente Tania, Marmol Inés, Lasheras Roberto, Sebastian Victor, Arruebo Manuel, Osada Jesús, Rodriguez-Yoldi María Jesús
Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón, Universidad de Zaragoza, E-50013 Zaragoza, Spain.
Departamento de Farmacología, Fisiología, Medicina Legal y Forense, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón, Universidad de Zaragoza, E-50013 Zaragoza, Spain.
Int J Mol Sci. 2024 Dec 4;25(23):13048. doi: 10.3390/ijms252313048.
Squalene, a triterpene found in extra virgin olive oil, has therapeutic properties in diseases related to oxidative stress, such as cancer. However, its hydrophobic nature and susceptibility to oxidation limit its bioavailability outside of olive oil. To expand its applications, alternative delivery methods are necessary. The objective of the present study was to examine the impact of squalene encapsulated in PLGA (poly(lactic-co-glycolic) acid) nanoparticles (PLGA + Sq) on the proliferation of human colon carcinoma Caco-2 cells, as well as its underlying mechanism of action. The findings demonstrated that PLGA + Sq exert no influence on differentiated cells; however, it is capable of reducing the proliferation of undifferentiated Caco-2 cells through apoptosis and cell cycle arrest in the G1 phase. This effect was initiated by the release of cytochrome c into the cytoplasm and the subsequent activation of caspase-3. Furthermore, squalene exhibited pro-oxidant activity, as evidenced by an increase in intracellular ROS (reactive oxygen species) levels. The results of the squalene effect on genes associated with cell death, inflammation, and the cell cycle indicate that its antiproliferative effect may be post-transcriptional. In conclusion, PLGA + Sq demonstrate an antiproliferative effect on Caco-2 cells through apoptosis by altering redox balance, suggesting squalene's potential as a functional food ingredient for colorectal cancer prevention.
角鲨烯是一种存在于特级初榨橄榄油中的三萜烯，在与氧化应激相关的疾病（如癌症）中具有治疗特性。然而，其疏水性和易氧化性限制了它在橄榄油之外的生物利用度。为了扩大其应用范围，需要采用替代的递送方法。本研究的目的是研究包裹在聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒中的角鲨烯（PLGA + Sq）对人结肠癌细胞Caco-2增殖的影响及其潜在作用机制。研究结果表明，PLGA + Sq对分化细胞没有影响；然而，它能够通过诱导细胞凋亡和使细胞周期停滞在G1期来减少未分化的Caco-2细胞的增殖。这种效应是由细胞色素c释放到细胞质中并随后激活caspase-3引发的。此外，角鲨烯表现出促氧化活性，细胞内活性氧（ROS）水平升高证明了这一点。角鲨烯对与细胞死亡、炎症和细胞周期相关基因的影响结果表明，其抗增殖作用可能是转录后水平的。总之，PLGA + Sq通过改变氧化还原平衡诱导细胞凋亡，对Caco-2细胞表现出抗增殖作用，这表明角鲨烯作为预防结直肠癌的功能性食品成分具有潜力。
