Mitochondrial transfer in PC-3 cells fingerprinted in ferroptosis sensitivity: a brand new approach targeting cancer metabolism
Mitochondrial transfer in PC-3 cells fingerprinted in ferroptosis sensitivity: a brand new approach targeting cancer metabolism
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DOI：
10.1007/s13577-023-00896-5
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发表时间：
2023-03-24
期刊：
影响因子：
4.3
通讯作者：
Roushandeh，Amaneh Mohammadi
中科院分区：
文献类型：
--
作者：
Nikoo，Amirsadegh;Roudkenar，Mehryar Habibi;Roushandeh，Amaneh Mohammadi
尽管最近的治疗进展，癌症仍然是世界范围内死亡的主要原因之一，线粒体功能障碍与癌症的发生和进展有关，沿着化疗抗性和铁凋亡细胞死亡失败;然而，线粒体在各种癌症类型中的重要性目前仍然是一个争论的问题。本研究的目的是确定将健康线粒体转移到侵袭性和快速增殖的前列腺癌（PC-3）细胞中的结果，然后评估有或没有铁凋亡诱导剂erastin的联合治疗的疗效。从这个意义上说，正常线粒体首先从人脐带来源的间充质干细胞、人脐静脉内皮细胞和人胚肾细胞中分离，然后转移到PC-3细胞和罗丹明6 G处理的表现出线粒体功能障碍的PC-3细胞中。接下来，分别使用细胞计数试剂盒-8和丙二醛测定脂质过氧化试剂盒测量细胞增殖和对顺铂的敏感性，沿着铁毒性损伤。观察到将健康线粒体转移到PC-3细胞中增加细胞增殖并挽救顺铂诱导的细胞死亡，但不挽救erastin诱导的铁凋亡，因为在线粒体转移中有效地增强了PC-3细胞中erastin介导的铁凋亡。因此，将健康的线粒体引入高度侵袭性和增殖的癌细胞中将被认为是多种癌症的全新治疗策略。
Despite recent therapeutic advancements, cancer remains one of the leading causes of death worldwide, with mitochondrial dysfunction being associated with cancer initiation and progression, along with chemotherapeutic resistance and ferroptotic cell death failure; however, the significance of mitochondria in various cancer types remains a matter of debate for the moment. The aim of this study is to ascertain the outcome of transferring healthy mitochondria into the aggressive and rapidly proliferating prostate cancer (PC-3) cells and afterwards evaluate the efficacy of combination therapy with or without the ferroptosis inducer erastin. In this sense, normal mitochondria were first isolated from human umbilical cord-derived mesenchymal stem cells, human umbilical vein endothelial cells, and human embryonic kidney cells and were later transferred into PC-3 cells and rhodamine 6G-treated PC-3 cells exhibiting mitochondrial dysfunction. Next, cell proliferation and sensitivity to cisplatin were measured using Cell Counting Kit-8 and the Malondialdehyde Assay Lipid Peroxidation Kit, respectively, along with ferroptotic damage. Transferring the healthy mitochondria into PC-3 cells was observed to increase cell proliferation and rescue the cisplatin-induced cell death, but not the erastin-induced ferroptosis, as in mitochondrial transfer effectively enhanced erastin-mediated ferroptosis in PC-3 cells. Hence, the introduction of healthy mitochondria into the highly aggressive and proliferating cancer cells would be deemed a brand new therapeutic strategy for a variety of cancers.