AlKahlout Amal, Fardoun Manal, Mesmar Joelle, Abdallah Rola, Badran Adnan, Nasser Suzanne A, Baydoun Serine, Kobeissy Firas, Shaito Abdullah, Iratni Rabah, Muhammad Khalid, Baydoun Elias, Eid Ali H
Kurome Therapeutics, Cincinnati, OH, United States.
Department of Biology, American University of Beirut, Beirut, Lebanon.
Front Oncol. 2022 Jun 30;12:922196. doi: 10.3389/fonc.2022.922196. eCollection 2022.
Breast cancer is the leading cause of cancer-related deaths among women. Among breast cancer types, triple negative breast cancer (TNBC) is the most aggressive, and is resistant to hormonal and chemotherapeutic treatments. As such, alternative approaches that may provide some benefit in fighting this debilitating pathology are critically needed; hence the utilization of herbal medicine. L., one of the most regularly consumed plants in the Mediterranean region, exhibits antiproliferative effect on several cancer cell lines. However, whether this herb modulates the malignant phenotype of TNBC remains poorly investigated. Here, we show that in MDA-MB-231, a TNBC cell line, L. aqueous extract (OSE) inhibited cellular viability, induced autophagy determined by the accumulation of lipidized LC3 II, and triggered apoptosis. We also show that OSE significantly promoted homotypic cell-cell adhesion while it decreased cellular migration, adhesion to fibronectin, and invasion of MDA-MB-231 cells. This was supported by decreased activity of focal adhesion kinase (FAK), reduced α2 integrin expression, and downregulation of secreted PgE, MMP2 and MMP-9, in OSE-treated cells. Finally, we also show that OSE significantly inhibited angiogenesis and downregulated the level of nitric oxide (NO) production. Our findings demonstrate the ability of OSE to attenuate the malignant phenotype of the MDA-MB-231 cells, thus presenting L. as a promising potential source for therapeutic compounds for TNBC.
乳腺癌是女性癌症相关死亡的主要原因。在乳腺癌类型中，三阴性乳腺癌（TNBC）最为侵袭性，且对激素和化疗治疗具有抗性。因此，迫切需要可能在对抗这种使人衰弱的病理状况中提供一些益处的替代方法；因此草药的利用受到关注。在地中海地区最常食用的植物之一，对几种癌细胞系表现出抗增殖作用。然而，这种草药是否调节TNBC的恶性表型仍研究不足。在这里，我们表明，在TNBC细胞系MDA-MB-231中，该植物水提取物（OSE）抑制细胞活力，通过脂化LC3 II的积累确定诱导自噬，并触发细胞凋亡。我们还表明，OSE显著促进同型细胞间粘附，同时降低细胞迁移、对纤连蛋白的粘附以及MDA-MB-231细胞的侵袭。在OSE处理的细胞中，粘着斑激酶（FAK）活性降低、α2整合素表达减少以及分泌的PgE、MMP2和MMP-9下调支持了这一点。最后，我们还表明，OSE显著抑制血管生成并下调一氧化氮（NO）产生水平。我们的研究结果证明了OSE减弱MDA-MB-231细胞恶性表型的能力，从而将该植物呈现为TNBC治疗化合物的有希望的潜在来源。
