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. 2017 Aug 5;277:109-114.
doi: 10.1016/j.toxlet.2017.06.006. Epub 2017 Jun 28.

Aclarubicin, an Anthracycline Anti-Cancer Drug, Fluorescently Contrasts Mitochondria and Reduces the Oxygen Consumption Rate in Living Human Cells

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Aclarubicin, an Anthracycline Anti-Cancer Drug, Fluorescently Contrasts Mitochondria and Reduces the Oxygen Consumption Rate in Living Human Cells

Haruka Iihoshi et al. Toxicol Lett. .

Abstract

Aclarubicin (Acla), an effective anthracycline chemotherapeutic agent for hematologic cancers and solid tumors, is documented to perturb chromatin function via histone eviction and DNA topoisomerase inhibition in the nucleus, but much less attention has been paid to cytotoxic function in the cytoplasm. Here, we showed that Acla emitted fluorescence and that human cervical cancer HeLa cells exposed to Acla exhibited bright fluorescence signals in the cytoplasm when fluorescence microscopy was performed using the red filter (excitation 530-550nm/emission 575nm). Intriguingly, most of the signals appeared to be partitioned and enriched in entangled tubule-like structures; moreover, these signals merged with the mitochondria-specific MitoTracker signals. Notably, analysis of mitochondrial respiratory activity revealed that the oxygen consumption rate was decreased in Acla-treated cells. These findings suggest that Acla accumulates efficiently in the mitochondria of living human cells and leads to mitochondrial dysfunction, implying a previously overlooked cytotoxicity of Acla in the cytoplasm and adding mechanistic insight of the anti-cancer activity, as well as the side effects, of Acla/anthracycline-based chemotherapy.

Keywords: Aclarubicin; Anthracycline; Anti-cancer activity; Chemotherapy; Mitochondria.

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