Treatment of K562 cells with 1,25-dihydroxyvitamin D3 induces distinct alterations in the expression of apoptosis-related genes BCL2, BAX, BCLXL, and p21.
Apoptosis, or programmed cell death, is a very important phenomenon in cytotoxicity induced by anticancer treatment. 1α,25-Dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)), the active metabolite of vitamin D, inhibits the growth of multiple types of cancer cells including breast, colon, and prostate cancer cell lines. We studied alterations in the mRNA expression levels of BCL2, BAX, CYC, BCL-XL, and VDR genes in the K562 chronic myeloid leukemia cell line in response to treatment with 1,25-(OH)(2)D(3). Morphological observation of K562 cells was evaluated by the staining with Wright's solution. Cell percentage at different phases of the cell cycle was measured, and apoptosis was measured by flow cytometry. The expression levels of the apoptosis-related genes were analyzed by real-time reverse transcription polymerase chain reaction. We found that treatment with 1,25-(OH)(2)D(3) down-regulates BCL2 and BCL-XL mRNA expressions, as well as up-regulates expressions of BAX and p21 mRNA. The expression pattern of CYC and VDR genes were not influenced. However, K562 cells treated with 1,25-(OH)(2)D(3) caused an arrest of cell cycle progression in G1 phase resulting in a decreased number of cells in the S phase, complemented by an accumulation of cells in the G0-G1 phases. Our data show the modulatory effects of 1,25-(OH)(2)D(3) treatment in apoptosis-related genes in K562 cells.
Kizildag
Sefa
S
Department of Medical Biology and Medical Genetics, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey. sefa.kizildag@deu.edu.tr
Ates
Halil
H
Kizildag
Servet
S
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D002117:Calcitriol / Q000502:physiology*; D002453:Cell Cycle / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis* / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020014:K562 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015854:Up-Regulation / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D051020:bcl-X Protein / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics
C494826:BAX protein, human; C494811:BCL2L1 protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D002117:Calcitriol