title: Per2 inhibits k562 leukemia cell growth in vitro and in vivo through cell cycle arrest and apoptosis induction.
abstract: Per2 regulates other molecular and biochemical processes beyond their established role in the regulation of the mammalian circadian clock, herein we investigated the growth inhibiting potential of Per2 in human K562 leukemia cells and the underlying mechanisms. The results showed that over-expression of Per2 induced not only cell cycle arrest at G2/M phase but also an increase in apoptosis, which was confirmed by characteristic morphological changes, FCM and evident DNA fragmentation. Further experiments confirmed both up-regulation of P53 and down-regulation of CylinB1and C-myc. On the other hand, while P53 was found to be down-regulated. CylinB1 and C-myc were up-regulated. after Per2 knockdown. In leukemia mice, Per2 transfection was shown to suppress cellular proliferation and accelerate apoptosis of K562 cells. Moreover, fewer leukemia cells were found to have infiltrated into the livers and spleens of the mice from the Per2 transfected group as compared with those from the control group. In summary, Per2 displayed a significant anti-tumor effect through cell cycle arrest and apoptosis induction in K562 cells. These data further support the emerging role of the circadian clock in critical aspects of cancer development and thorough research is underway on the mechanism of Per2 in the leukemia.
authors: Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Chongqing Medical University, Chongqing, People's Republic of China.
authors: Cheng-ming
authors: CM
authors: Sun
authors: Shi-feng
authors: SF
authors: Huang
authors: Jian-ming
authors: JM
authors: Zeng
authors: Din-bing
authors: DB
authors: Liu
authors: Qing
authors: Q
authors: Xiao
authors: Wen-jun
authors: WJ
authors: Tian
authors: Xi-dan
authors: XD
authors: Zhu
authors: Zong-gan
authors: ZG
authors: Huang
authors: Wen-li
authors: WL
authors: Feng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D056744:Cyclin B1 / Q000096:biosynthesis; D053938:DNA Fragmentation; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D056744:Cyclin B1; C489427:MYC protein, human; C421902:PER2 protein, human; D056950:Period Circadian Proteins; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53