Celik Aybuke, Orfany Arzoo, Dearling Jason, Del Nido Pedro J, McCully James D, Bakar-Ates Filiz
Department of Biochemistry, Faculty of Pharmacy, Ankara University, Ankara, Turkey; Department of Cardiac Surgery, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Department of Cardiac Surgery, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Biomed Pharmacother. 2023 May;161:114524. doi: 10.1016/j.biopha.2023.114524. Epub 2023 Mar 20.
Prostate and ovarian cancers affect the male and female reproductive organs and are among the most common cancers in developing countries. Previous studies have demonstrated that cancer cells have a high rate of aerobic glycolysis that is present in nearly all invasive human cancers and persists even under normoxic conditions. Aerobic glycolysis has been correlated with chemotherapeutic resistance and tumor aggressiveness. These data suggest that mitochondrial dysfunction may confer a significant proliferative advantage during the somatic evolution of cancer. In this study we investigated the effect of direct mitochondria transplantation on cancer cell proliferation and chemotherapeutic sensitivity in prostate and ovarian cancer models, both in vitro and in vivo. Our results show that the transplantation of viable, respiration competent mitochondria has no effect on cancer cell proliferation but significantly decreases migration and alters cell cycle checkpoints. Our results further demonstrate that mitochondrial transplantation significantly increases chemotherapeutic sensitivity, providing similar apoptotic levels with low-dose chemotherapy as that achieved with high-dose chemotherapy. These results suggest that mitochondria transplantation provides a novel approach for early prostate and ovarian cancer therapy, significantly increasing chemotherapeutic sensitivity in in vitro and in vivo murine models.
前列腺癌和卵巢癌分别影响男性和女性生殖器官，是发展中国家最常见的癌症之一。先前的研究表明，癌细胞具有较高的有氧糖酵解速率，几乎所有侵袭性人类癌症中都存在这种现象，甚至在常氧条件下也持续存在。有氧糖酵解与化疗耐药性和肿瘤侵袭性相关。这些数据表明，线粒体功能障碍可能在癌症的体细胞进化过程中赋予显著的增殖优势。在本研究中，我们在体外和体内前列腺癌及卵巢癌模型中，研究了直接线粒体移植对癌细胞增殖和化疗敏感性的影响。我们的结果表明，移植有活力、具备呼吸功能的线粒体对癌细胞增殖没有影响，但能显著减少迁移并改变细胞周期检查点。我们的结果进一步证明，线粒体移植显著提高化疗敏感性，低剂量化疗所达到的凋亡水平与高剂量化疗相似。这些结果表明，线粒体移植为早期前列腺癌和卵巢癌治疗提供了一种新方法，在体外和体内小鼠模型中显著提高了化疗敏感性。
