Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland.
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Int J Mol Sci. 2024 Jul 16;25(14):7764. doi: 10.3390/ijms25147764.
Breast cancer is a major malignancy among women, characterized by a high mortality rate. The available literature evidence indicates that selenium, as a trace element, has chemopreventive properties against many types of cancer; as such, compounds containing it in their structure may potentially exhibit anticancer activity. Accordingly, we have undertaken a study to evaluate the effects of novel selenoesters (EDAG-1, -7, -8, -10) on MCF-7 and MDA-MB-231 breast cancer cells. Our analysis included investigations of cell proliferation and viability as well as cytometric determinations of apoptosis/autophagy induction, changes in mitochondrial membrane polarity (ΔΨ), caspase 3/7, 8, and 9 activities, and Bax, Bcl-2, p53, Akt, AMPK, and LC3A/B proteins. The obtained data revealed that the tested derivatives are highly cytotoxic and inhibit cell proliferation even at nanomolar doses (0.41-0.79 µM). Importantly, their strong proapoptotic properties (↑ caspase 3/7) are attributable to the effects on both the extrinsic (↑ caspase 8) and intrinsic (↓ ΔΨ and Bcl-2, ↑ Bax, p53, and caspase 9) pathways of apoptosis. Moreover, the tested compounds are autophagy activators (↓ Akt, ↑ autophagosomes and autolysosomes, AMPK, LC3A/B). In summary, the potent anticancer activity suggests that the tested compounds may be promising drug candidates for future breast cancer therapy.
乳腺癌是女性中的一种主要恶性肿瘤，其死亡率较高。现有文献证据表明，硒作为一种微量元素，对许多类型的癌症具有化学预防作用；因此，其结构中含有硒的化合物可能具有抗癌活性。有鉴于此，我们进行了一项研究，以评估新型硒酯（EDAG-1、-7、-8、-10）对 MCF-7 和 MDA-MB-231 乳腺癌细胞的影响。我们的分析包括对细胞增殖和活力的研究以及细胞凋亡/自噬诱导的细胞计数测定、线粒体膜极性（ΔΨ）变化、caspase 3/7、8 和 9 活性以及 Bax、Bcl-2、p53、Akt、AMPK 和 LC3A/B 蛋白的变化。所得数据表明，所测试的衍生物具有高度细胞毒性，甚至在纳摩尔剂量（0.41-0.79 μM）下也能抑制细胞增殖。重要的是，它们强烈的促凋亡特性（↑caspase 3/7）归因于对外源性（↑caspase 8）和内源性（↓ΔΨ和 Bcl-2，↑Bax、p53 和 caspase 9）凋亡途径的影响。此外，测试的化合物是自噬激活剂（↓Akt，↑自噬体和自溶体，AMPK，LC3A/B）。总之，强大的抗癌活性表明，所测试的化合物可能是未来乳腺癌治疗的有前途的候选药物。
