西西里葡萄渣提取物的抗肿瘤潜力:ROS 促成的自噬与细胞凋亡之间的平衡

IF 4.8 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Biomolecules Pub Date : 2024-09-03 DOI:10.3390/biom14091111
Federica Affranchi, Diana Di Liberto, Marianna Lauricella, Antonella D’Anneo, Giuseppe Calvaruso, Giovanni Pratelli, Daniela Carlisi, Anna De Blasio, Luisa Tesoriere, Michela Giuliano, Antonietta Notaro, Sonia Emanuele
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引用次数: 0

摘要

从循环经济的角度来看,回收废品用于人类健康是非常有益的。在生物活性植物化合物的健康益处中,葡萄渣是具有潜在抗肿瘤特性的生物活性分子的珍贵来源。在这里,我们描述了西西里葡萄渣水醇提取物(HE)对结肠癌和乳腺癌细胞的影响。水醇提取物成分的特征表明,它主要含有花青素和酚酸。HE 处理能更有效地降低结肠癌细胞的存活率,而乳腺癌细胞似乎更具抵抗力。事实上,结肠癌细胞会发生凋亡,表现为 DNA 断裂、caspase-3 激活和 PARP1 降解,而乳腺癌细胞似乎不会发生凋亡。为了阐明其潜在机制,研究人员对活性氧(ROS)进行了评估。有趣的是,两种细胞系中的 ROS 都增加了,但在结肠癌中,细胞的 ROS 迅速增加,并随着时间的推移逐渐减少,而在乳腺癌中,细胞的 ROS 增加持续到 24 小时。这种效应与诱导有利于生存的自噬有关,表现为自噬体的形成、自噬标记物的增加以及抗氧化剂 NAC 的保护作用。自噬抑制剂巴佛洛霉素 A1 能显著增强 HE 对乳腺癌细胞的作用,但对结肠癌细胞没有作用。总之,我们的数据证明了 HE 对肿瘤细胞的疗效取决于 ROS 介导的自噬和细胞凋亡之间的平衡。因此,抑制促进存活的自噬可能是一种工具,可用于靶向那些对 HE 作用有较强抵抗力的细胞。
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The Antitumor Potential of Sicilian Grape Pomace Extract: A Balance between ROS-Mediated Autophagy and Apoptosis
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.
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来源期刊
Biomolecules
Biomolecules Biochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
9.40
自引率
3.60%
发文量
1640
审稿时长
18.28 days
期刊介绍: Biomolecules (ISSN 2218-273X) is an international, peer-reviewed open access journal focusing on biogenic substances and their biological functions, structures, interactions with other molecules, and their microenvironment as well as biological systems. Biomolecules publishes reviews, regular research papers and short communications.  Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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