Doxorubicin-transferrin conjugate alters mitochondrial homeostasis and energy metabolism in human breast cancer cells.
Doxorubicin-transferrin conjugate alters mitochondrial homeostasis and energy metabolism in human breast cancer cells.
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DOI：
10.1038/s41598-021-84146-4
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发表时间：
2021-02-25
影响因子：
4.6
通讯作者：
Szwed M
中科院分区：
文献类型：
--
作者：
Wigner P;Zielinski K;Labieniec-Watala M;Marczak A;Szwed M
阿霉素 (DOX) 被认为是最有效的化疗药物之一，但其临床使用有一些局限性，包括心肌病和细胞对该药物的耐药性。然而，通过使用转铁蛋白（Tf）作为药物载体，可以减少阿霉素的副作用以及耐药性。本研究的主要目的是确定 DOX-Tf 缀合物治疗对线粒体功能影响的确切性质和程度，特别是在人乳腺癌细胞中。我们评估了 DOX-Tf 缀合物作为药物递送系统的潜力，并使用 MTT 测定和 ATP 测量监测其细胞毒性。此外，我们测量了线粒体功能和氧化应激标记物的变化。 DOX-Tf 的作用在 MDA-MB-231（三阴性乳腺癌细胞）中最为明显，而非癌内皮 HUVEC-ST 细胞对 DOX-Tf 缀合物的抵抗力比对游离 DOX 治疗的抵抗力更强。两种研究的乳腺癌细胞系的不同敏感性与其细胞抗氧化系统的功能和雌激素受体的表达相对应。我们的数据还显示，结合物治疗介导自由基的产生并改变乳腺癌细胞中的线粒体生物能。
Doxorubicin (DOX) is considered one of the most powerful chemotherapeutic agents but its clinical use has several limitations, including cardiomyopathy and cellular resistance to the drug. By using transferrin (Tf) as a drug carrier, however, the adverse effects of doxorubicin as well as drug resistance can be reduced. The main objective of this study was to determine the exact nature and extent to which mitochondrial function is influenced by DOX–Tf conjugate treatment, specifically in human breast adenocarcinoma cells. We assessed the potential of DOX–Tf conjugate as a drug delivery system, monitoring its cytotoxicity using the MTT assay and ATP measurements. Moreover, we measured the alterations of mitochondrial function and oxidative stress markers. The effect of DOX–Tf was the most pronounced in MDA-MB-231, triple-negative breast cancer cells, whereas non-cancer endothelial HUVEC-ST cells were more resistant to DOX–Tf conjugate than to free DOX treatment. A different sensitivity of two investigate breast cancer cell lines corresponded to the functionality of their cellular antioxidant systems and expression of estrogen receptors. Our data also revealed that conjugate treatment mediated free radical generation and altered the mitochondrial bioenergetics in breast cancer cells.
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影响因子：
7.4
作者：
Gilliam, Laura A. A.;Fisher-Wellman, Kelsey H.;Lin, Chien-Te;Maples, Jill M.;Cathey, Brook L.;Neufer, P. Darrell
通讯作者：
Neufer, P. Darrell
影响因子：
3.8
作者：
Marques O;Porto G;Rêma A;Faria F;Cruz Paula A;Gomez-Lazaro M;Silva P;Martins da Silva B;Lopes C
通讯作者：
Lopes C
影响因子：
4.3
作者：
Chifman J;Arat S;Deng Z;Lemler E;Pino JC;Harris LA;Kochen MA;Lopez CF;Akman SA;Torti FM;Torti SV;Laubenbacher R
通讯作者：
Laubenbacher R
影响因子：
5.2
作者：
Sweeney EE;Fan P;Jordan VC
通讯作者：
Jordan VC
影响因子：
5.4
作者：
Soe, Zar Chi;Kwon, Jun Bum;Kim, Jong Oh
通讯作者：
Kim, Jong Oh