Department of Medicine, Division of Hematology, Oncology and Blood and Marrow Transplantation, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States; Institute of Cancer Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Department of Medicine, Division of Hematology, Oncology and Blood and Marrow Transplantation, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States.
EBioMedicine. 2017 Apr;18:41-49. doi: 10.1016/j.ebiom.2017.02.011. Epub 2017 Feb 16.
High-dose chemotherapies to treat multiple myeloma (MM) can be life-threatening due to toxicities to normal cells and there is a need to target only tumor cells and/or lower standard drug dosage without losing efficacy. We show that pharmacologically-dosed ascorbic acid (PAA), in the presence of iron, leads to the formation of highly reactive oxygen species (ROS) resulting in cell death. PAA selectively kills CD138 MM tumor cells derived from MM and smoldering MM (SMM) but not from monoclonal gammopathy undetermined significance (MGUS) patients. PAA alone or in combination with melphalan inhibits tumor formation in MM xenograft mice. This study shows PAA efficacy on primary cancer cells and cell lines in vitro and in vivo.
高剂量化疗治疗多发性骨髓瘤(MM)可能会因对正常细胞的毒性而危及生命,因此需要靶向肿瘤细胞和/或降低标准药物剂量,同时不降低疗效。我们发现,在铁存在的情况下,药物剂量的抗坏血酸(PAA)会导致高活性氧(ROS)的形成,从而导致细胞死亡。PAA 选择性地杀死 CD138 MM 肿瘤细胞,这些细胞来源于 MM 和冒烟型 MM(SMM),而不是来源于意义未明的单克隆丙种球蛋白血症(MGUS)患者。PAA 单独或与美法仑联合使用可抑制 MM 异种移植小鼠的肿瘤形成。本研究显示了 PAA 在体外和体内对原发性癌细胞和细胞系的疗效。