Single and double modified salinomycin analogs target stem-like cells in 2D and 3D breast cancer models.
Single and double modified salinomycin analogs target stem-like cells in 2D and 3D breast cancer models.
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DOI：
10.1016/j.biopha.2021.111815
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
MacNicol AM
中科院分区：
文献类型：
--
作者：
Urbaniak A;Reed MR;Fil D;Moorjani A;Heflin S;Antoszczak M;Sulik M;Huczyński A;Kupsik M;Eoff RL;MacNicol MC;Chambers TC;MacNicol AM
乳腺癌仍然是妇女的主要癌症之一。癌症干细胞（CSC）是肿瘤起始细胞，其驱动疾病的进展、转移和复发。CSC对常规化疗和放疗具有抗性，并且它们在这种治疗中存活的能力使得肿瘤重建成为可能。转移是乳腺癌女性死亡的主要原因，因此治疗的进展将取决于靶向CSC的治疗策略。盐霉素（SAL）是一种天然存在的聚醚离子载体抗生素，因其对多种类型的肿瘤细胞具有抗癌活性而闻名。在本工作中，筛选了17个C1-单和C1/C20-双修饰的SAL类似物的文库，以鉴定具有改善的抗乳腺CSC活性的化合物。与SAL（IC 50为4.9 ± 1.6 μM）相比，6种单修饰类似物和2种双修饰类似物对乳腺癌细胞系MDA-MB-231更有效（IC 50范围为1.1 ± 0.1至1.4 ± 0.2 μ M）。发现双重修饰的化合物17比SAL更有效地对抗NCI-60人类肿瘤细胞系小组中的大多数癌细胞系。化合物17在抑制MDA-MB-231细胞的细胞迁移和细胞更新特性以及诱导单层（2D）和类器官（3D）培养物中的CD 44 +/CD 24 −/低干细胞样亚群的选择性丧失方面比SAL更有效。目前的研究结果突出了SAL类似物对乳腺CSC的治疗潜力，并确定了值得进一步研究和临床开发的精选化合物。
Breast cancer remains one of the leading cancers among women. Cancer stem cells (CSCs) are tumor-initiating cells which drive progression, metastasis, and reoccurrence of the disease. CSCs are resistant to conventional chemo- and radio-therapies and their ability to survive such treatment enables tumor reestablishment. Metastasis is the main cause of mortality in women with breast cancer, thus advances in treatment will depend on therapeutic strategies targeting CSCs. Salinomycin (SAL) is a naturally occurring polyether ionophore antibiotic known for its anticancer activity towards several types of tumor cells. In the present work, a library of 17 C1-single and C1/C20-double modified SAL analogs was screened to identify compounds with improved activity against breast CSCs. Six single- and two double-modified analogs were more potent (IC50 range of 1.1 ± 0.1 to 1.4 ± 0.2 μM) toward the breast cancer cell line MDA-MB-231 compared to SAL (IC50 of 4.9 ± 1.6 μM). Double-modified compound 17 was found to be more efficacious than SAL against the majority of cancer cell lines in the NCI-60 Human Tumor Cell Line Panel. Compound 17 was more potent than SAL in inhibiting cell migration and cell renewal properties of MDA-MB-231 cells, as well as inducing selective loss of the CD44+/CD24−/low stem-cell-like subpopulation in both monolayer (2D) and organoid (3D) culture. The present findings highlight the therapeutic potential of SAL analogs towards breast CSCs and identify select compounds that merit further study and clinical development.
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DOI：
10.3390/molecules191219435
发表时间：
2014-11-25
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Antoszczak M;Maj E;Napiórkowska A;Stefańska J;Augustynowicz-Kopeć E;Wietrzyk J;Janczak J;Brzezinski B;Huczyński A
通讯作者：
Huczyński A
影响因子：
3.7
作者：
An H;Kim JY;Oh E;Lee N;Cho Y;Seo JH
通讯作者：
Seo JH
影响因子：
6.7
作者：
Antoszczak, Michal;Urbaniak, Alicja;Strand, Daniel
通讯作者：
Strand, Daniel
影响因子：
6.7
作者：
Antoszczak, Michal;Steverding, Dietmar;Huczynski, Adam
通讯作者：
Huczynski, Adam
影响因子：
4
作者：
Huang, Xiaoli;Borgstrom, Bjorn;Strand, Daniel
通讯作者：
Strand, Daniel