Sodium selenite induces apoptosis in acute promyelocytic leukemia-derived NB4 cells by a caspase-3-dependent mechanism and a redox pathway different from that of arsenic trioxide.
Two relatively recent discoveries stand behind our current effort to investigate the effects of the chemopreventive agent, selenium, on the proliferation and survival of NB4 cells. The first is that certain selenium compounds such as sodium selenite have pro-oxidant ability to catalyze the oxidation of thiols and simultaneously generate superoxide. The second lies in the exquisite susceptibility of NB4 cells to arsenic trioxide-induced, reactive oxygen species (ROS)-mediated apoptosis due to less efficiency of the cellular defense system. In this study, we demonstrated that sodium selenite could induce apoptosis in NB4 cells via the classic mitochondrial pathway involving caspase-3 activation and Bcl-2 cleavage. An increase in the basal cellular glutathione (GSH) content rendered NB4 cells resistant to arsenic trioxide, but could sensitize NB4 cells to sodium selenite. Moreover, combined treatment of NB4 cells with all- trans retinoic acid (ATRA) at low concentration and sodium selenite exhibited a synergistic effect on apoptosis induction. Together, our results suggest that selenite is a promising candidate for treatment of acute promyelocytic leukemia (APL) and the mechanism underlying its anticancer effects warrants further investigation.
Zuo
Lu
L
Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, 100730, Beijing, People's Republic of China.
Li
Jian
J
Yang
Yang
Y
Wang
Xuan
X
Shen
Ti
T
Xu
Cai-min
CM
Zhang
Zhi-nan
ZN
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010087:Oxides / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018038:Sodium Selenite / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D014212:Tretinoin; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D018038:Sodium Selenite; D000077237:Arsenic Trioxide