Lappano Rosamaria, Sebastiani Anna, Cirillo Francesca, Rigiracciolo Damiano Cosimo, Galli Giulia Raffaella, Curcio Rosita, Malaguarnera Roberta, Belfiore Antonino, Cappello Anna Rita, Maggiolini Marcello
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy.
Cell Death Discov. 2017 Sep 18;3:17063. doi: 10.1038/cddiscovery.2017.63. eCollection 2017.
The saturated medium-chain fatty-acid lauric acid (LA) has been associated to certain health-promoting benefits of coconut oil intake, including the improvement of the quality of life in breast cancer patients during chemotherapy. As it concerns the potential to hamper tumor growth, LA was shown to elicit inhibitory effects only in colon cancer cells. Here, we provide novel insights regarding the molecular mechanisms through which LA triggers antiproliferative and pro-apoptotic effects in both breast and endometrial cancer cells. In particular, our results demonstrate that LA increases reactive oxygen species levels, stimulates the phosphorylation of EGFR, ERK and c-Jun and induces the expression of c-fos. In addition, our data evidence that LA via the Rho-associated kinase-mediated pathway promotes stress fiber formation, which exerts a main role in the morphological changes associated with apoptotic cell death. Next, we found that the increase of p21 expression, which occurs upon LA exposure in a p53-independent manner, is involved in the apoptotic effects prompted by LA in both breast and endometrial cancer cells. Collectively, our findings may pave the way to better understand the anticancer action of LA, although additional studies are warranted to further corroborate its usefulness in more comprehensive therapeutic approaches.
饱和中链脂肪酸月桂酸（LA）与摄入椰子油带来的某些促进健康的益处有关，包括改善乳腺癌患者化疗期间的生活质量。关于其抑制肿瘤生长的潜力，LA仅在结肠癌细胞中显示出抑制作用。在此，我们提供了关于LA在乳腺癌和子宫内膜癌细胞中触发抗增殖和促凋亡作用的分子机制的新见解。特别是，我们的结果表明，LA会增加活性氧水平，刺激表皮生长因子受体（EGFR）、细胞外信号调节激酶（ERK）和c-Jun的磷酸化，并诱导c-fos的表达。此外，我们的数据证明，LA通过Rho相关激酶介导的途径促进应力纤维形成，这在与凋亡性细胞死亡相关的形态变化中起主要作用。接下来，我们发现，LA暴露后以p53非依赖方式发生的p21表达增加，与LA在乳腺癌和子宫内膜癌细胞中引发的凋亡作用有关。总体而言，我们的发现可能为更好地理解LA的抗癌作用铺平道路，尽管还需要进一步的研究来进一步证实其在更全面治疗方法中的有效性。
