Mizutani Hideki, Hotta Saki, Nishimoto Ayano, Ikemura Kenji, Miyazawa Daisuke, Ikeda Yoshiaki, Maeda Tohru, Yoshikawa Masae, Hiraku Yusuke, Kawanishi Shosuke
College of Pharmacy, Kinjo Gakuin University, Nagoya, Japan
College of Pharmacy, Kinjo Gakuin University, Nagoya, Japan.
Anticancer Res. 2017 Nov;37(11):6063-6069. doi: 10.21873/anticanres.12054.
BACKGROUND/AIM: Pirarubicin (THP) has shown equal or superior cytotoxicity compared to doxorubicin. One of the main anticancer actions of doxorubicin is believed to be involved in ROS (reactive oxygen species) generation. Therefore, the anticancer mechanisms of THP may involve ROS generation. The aim of this study was to clarify the mechanisms of THP-induced apoptosis through ROS generation.
We analyzed the apoptotic events induced by THP in HL-60 cells and HP100 cells, hydrogen peroxide (HO)-resistant cells derived from HL-60.
The apparent cytotoxicity could be detected at above 0.1 μM in HL-60 cells after 24-h incubation, whereas it was suppressed under these conditions in HP100 cells. In HP100 cells, THP-induced apoptosis, evaluated by DNA ladder formation, HO generation, mitochondrial membrane potential decrease and caspase-3/7 activity, was suppressed or delayed compared to those of HL-60 cells.
These findings can be explained by the involvement of HO generation in the THP apoptotic pathway. This is the first report on THP-induced apoptosis through the HO generation.
背景/目的：吡柔比星（THP）已显示出与多柔比星相当或更强的细胞毒性。多柔比星的主要抗癌作用之一被认为与活性氧（ROS）的产生有关。因此，THP的抗癌机制可能涉及ROS的产生。本研究的目的是阐明THP通过ROS产生诱导细胞凋亡的机制。
我们分析了THP在HL-60细胞和HP100细胞（源自HL-60的过氧化氢（HO）抗性细胞）中诱导的凋亡事件。
在HL-60细胞中，孵育24小时后，在浓度高于0.1μM时可检测到明显的细胞毒性，而在这些条件下HP100细胞中的细胞毒性受到抑制。在HP100细胞中，通过DNA梯状条带形成、HO产生、线粒体膜电位降低和半胱天冬酶-3/7活性评估，THP诱导的细胞凋亡与HL-60细胞相比受到抑制或延迟。
这些发现可以通过HO产生参与THP凋亡途径来解释。这是关于THP通过HO产生诱导细胞凋亡的首次报道。
