乳腺癌是女性的主要恶性肿瘤,特点是死亡率高。现有的文献证据表明硒,作为一种微量元素,对许多类型的癌症具有化学预防特性;因此,在其结构中含有它的化合物可能潜在地表现出抗癌活性。因此,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,线粒体膜极性变化(ΔkW),caspase3/7、8和9活性,还有Bax,Bcl-2,p53,Akt,AMPK,和LC3A/B蛋白。获得的数据表明,即使在纳摩尔剂量(0.41-0.79µM)下,测试的衍生物也具有高细胞毒性并抑制细胞增殖。重要的是,它们强烈的促凋亡特性(^caspase3/7)可归因于对外源性(^caspase8)和内源性(^ΔWm和Bcl-2,^Bax,p53和半胱天冬酶9)凋亡途径。此外,受试化合物是自噬激活剂(△Akt,自噬体和自溶酶体,AMPK,LC3A/B)。总之,有效的抗癌活性表明,所测试的化合物可能是未来乳腺癌治疗的有希望的候选药物。
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 (ΔΨm), 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 (↓ ΔΨm 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.