Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, 90128 Palermo, Italy.
Department of Biomedicine, Neurosciences and Advanced Diagnostics (BIND), Institute of Biochemistry, University of Palermo, Via del Vespro 129, 90127 Palermo, Italy.
Biomolecules. 2024 Sep 3;14(9):1111. doi: 10.3390/biom14091111.
From the perspective of circular economy, it is extremely useful to recycle waste products for human health applications. Among the health-beneficial properties of bioactive phyto-compounds, grape pomace represents a precious source of bioactive molecules with potential antitumor properties. Here, we describe the effects of a Sicilian grape pomace hydroalcoholic extract (HE) in colon and breast cancer cells. The characterization of HE composition revealed the predominance of anthoxanthins and phenolic acids. HE treatment was more effective in reducing the viability of colon cancer cells, while breast cancer cells appeared more resistant. Indeed, while colon cancer cells underwent apoptosis, as shown by DNA fragmentation, caspase-3 activation, and PARP1 degradation, breast cancer cells seemed to not undergo apoptosis. To elucidate the underlying mechanisms, reactive oxygen species (ROS) were evaluated. Interestingly, ROS increased in both cell lines but, while in colon cancer, cells' ROS rapidly increased and progressively diminished over time, in breast cancer, cells' ROS increase was persistent up to 24 h. This effect was correlated with the induction of pro-survival autophagy, demonstrated by autophagosomes formation, autophagic markers increase, and protection by the antioxidant NAC. The autophagy inhibitor bafilomycin A1 significantly increased the HE effects in breast cancer cells but not in colon cancer cells. Overall, our data provide evidence that HE efficacy in tumor cells depends on a balance between ROS-mediated autophagy and apoptosis. Therefore, inhibiting pro-survival autophagy may be a tool to target those cells that appear more resistant to the effect of HE.
从循环经济的角度来看，回收有益于人类健康的产品用于应用具有重要意义。在具有生物活性的植物化合物的有益健康特性中，葡萄渣代表了具有潜在抗肿瘤特性的生物活性分子的宝贵来源。在这里，我们描述了一种西西里葡萄渣水醇提取物（HE）对结肠和乳腺癌细胞的影响。HE 组成的特征表明，蒽酮和酚酸占主导地位。HE 处理在降低结肠癌细胞活力方面更有效，而乳腺癌细胞似乎更具抗性。事实上，虽然结肠癌细胞经历了细胞凋亡，如 DNA 片段化、caspase-3 激活和 PARP1 降解所示，但乳腺癌细胞似乎没有经历细胞凋亡。为了阐明潜在的机制，评估了活性氧（ROS）。有趣的是，两种细胞系中的 ROS 都增加了，但在结肠癌细胞中，细胞的 ROS 迅速增加并随着时间的推移逐渐减少，而在乳腺癌细胞中，ROS 的增加持续到 24 小时。这种效应与诱导促生存自噬有关，这表现为自噬体形成、自噬标记物增加以及抗氧化剂 NAC 的保护。自噬抑制剂巴弗洛霉素 A1 显著增加了 HE 对乳腺癌细胞的作用，但对结肠癌细胞没有作用。总体而言，我们的数据提供了证据，表明 HE 在肿瘤细胞中的功效取决于 ROS 介导的自噬和细胞凋亡之间的平衡。因此，抑制促生存自噬可能是针对那些对 HE 作用更具抗性的细胞的一种工具。
