Skip to main content
Top
Published in: Annals of Hematology 1/2010

01-01-2010 | Original Article

Treatment of K562 cells with 1,25-dihydroxyvitamin D3 induces distinct alterations in the expression of apoptosis-related genes BCL2, BAX, BCLXL, and p21

Authors: Sefa Kizildag, Halil Ates, Servet Kizildag

Published in: Annals of Hematology | Issue 1/2010

Login to get access

Abstract

Apoptosis, or programmed cell death, is a very important phenomenon in cytotoxicity induced by anticancer treatment. 1α,25-Dihydroxyvitamin D3 (1,25-(OH)2D3), 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)2D3. 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)2D3 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)2D3 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)2D3 treatment in apoptosis-related genes in K562 cells.
Literature
1.
go back to reference Colston KW, Colston MJ, Feldman D (1981) 1, 25-Dihydroxyvitamin D3 and malignant melanoma: the presence of receptors and inhibition of cell growth in culture. Endocrinology 108:1083–1086CrossRefPubMed Colston KW, Colston MJ, Feldman D (1981) 1, 25-Dihydroxyvitamin D3 and malignant melanoma: the presence of receptors and inhibition of cell growth in culture. Endocrinology 108:1083–1086CrossRefPubMed
3.
go back to reference Elstner E, Linker-Israeli M, Umiel T et al (1995) Combination of a potent 20-epi-vitamin D3 analog (KH 1060) with 9-cis-retinoic acid irreversibly inhibits clonal growth, decreases bcl-2 expression, and induces apoptosis in HL-60 leukemic cells. Cancer Res 56:3570–3576 Elstner E, Linker-Israeli M, Umiel T et al (1995) Combination of a potent 20-epi-vitamin D3 analog (KH 1060) with 9-cis-retinoic acid irreversibly inhibits clonal growth, decreases bcl-2 expression, and induces apoptosis in HL-60 leukemic cells. Cancer Res 56:3570–3576
5.
8.
go back to reference Chen TC, Schwartz GG, Burnstein KL, Lokeshwar BL, Holick MF (2000) The in vitro evaluation of 25-hydroxyvitamin D3 and 19-nor-1, 25-dihydroxyvitamin D2 as therapeutics agents for prostate cancer. Clin Cancer Res 6:901–908PubMed Chen TC, Schwartz GG, Burnstein KL, Lokeshwar BL, Holick MF (2000) The in vitro evaluation of 25-hydroxyvitamin D3 and 19-nor-1, 25-dihydroxyvitamin D2 as therapeutics agents for prostate cancer. Clin Cancer Res 6:901–908PubMed
9.
go back to reference Skarosi S, Abraham C, Bissonette M, Scaglione-Sewel B, Siltrin MD, Brastius TA (1997) 1, 25-Dihydroxyvitamin D3 stimulates apoptosis in CaCo-2 cells. Gastroenterology 112:A608 Skarosi S, Abraham C, Bissonette M, Scaglione-Sewel B, Siltrin MD, Brastius TA (1997) 1, 25-Dihydroxyvitamin D3 stimulates apoptosis in CaCo-2 cells. Gastroenterology 112:A608
14.
go back to reference Seol JG, Park WH, Kim ES et al (2000) Effect of a novel vitamin D3 analog, EB1089 on G1 cell cycle regulatory proteins in HL-60 cells. Int J Oncol 16:315–320PubMed Seol JG, Park WH, Kim ES et al (2000) Effect of a novel vitamin D3 analog, EB1089 on G1 cell cycle regulatory proteins in HL-60 cells. Int J Oncol 16:315–320PubMed
15.
go back to reference Liu M, Lee M-H, Cohen M, Bommakanti M, Freedman LP (1996) Transcriptional activation of the cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelocytic cell line U937. Genes Dev 10:142–153. doi:10.1101/gad.10.2.142 CrossRefPubMed Liu M, Lee M-H, Cohen M, Bommakanti M, Freedman LP (1996) Transcriptional activation of the cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelocytic cell line U937. Genes Dev 10:142–153. doi:10.​1101/​gad.​10.​2.​142 CrossRefPubMed
17.
go back to reference Reitsma PH, Rothberg PG, Astrin SM, Trial J, Bar-Shavit Z, Hall A, Teitelbaum SL, Kahn AJ (1983) Regulation of myc gene expression in HL-60 leukaemia cells by a vitamin D metabolite. Nature 306:492–494. doi:10.1038/306492a0 CrossRefPubMed Reitsma PH, Rothberg PG, Astrin SM, Trial J, Bar-Shavit Z, Hall A, Teitelbaum SL, Kahn AJ (1983) Regulation of myc gene expression in HL-60 leukaemia cells by a vitamin D metabolite. Nature 306:492–494. doi:10.​1038/​306492a0 CrossRefPubMed
19.
go back to reference Mørk Hansen C, Hamberg KJ, Binderup E, Binderup L (2000) Seocalcitol (EB 1089): a vitamin D analogue of anti-cancer potential. Background, design, synthesis, pre-clinical and clinical evaluation. Current Pharmaceutical Design 6:881–906 Mørk Hansen C, Hamberg KJ, Binderup E, Binderup L (2000) Seocalcitol (EB 1089): a vitamin D analogue of anti-cancer potential. Background, design, synthesis, pre-clinical and clinical evaluation. Current Pharmaceutical Design 6:881–906
23.
go back to reference Moore DC, Carter DL, Bhandal AK, Studzinski GP (1991) Inhibition by 1, 25 dihydroxyvitamin D3 of chemically induced erythroid differentiation of K562 leukemia cells. Blood 77:1452–1461PubMed Moore DC, Carter DL, Bhandal AK, Studzinski GP (1991) Inhibition by 1, 25 dihydroxyvitamin D3 of chemically induced erythroid differentiation of K562 leukemia cells. Blood 77:1452–1461PubMed
25.
go back to reference Diaz GD, Paraskeva C, Thomas MG, Binderup L, Hague A (2000) Apoptosis is induced by the active metabolite of vitamin D3 and its analog EB1089 in colorectal adenoma and carcinoma cells: possible implications for prevention and therapy. Cancer Res 60:2304–2312PubMed Diaz GD, Paraskeva C, Thomas MG, Binderup L, Hague A (2000) Apoptosis is induced by the active metabolite of vitamin D3 and its analog EB1089 in colorectal adenoma and carcinoma cells: possible implications for prevention and therapy. Cancer Res 60:2304–2312PubMed
26.
go back to reference Mathiasen IS, Lademann U, Jaattela M (1999) Apoptosis induced by vitamin D compounds in breast cancer is inhibited by Bcl-2 but doesn't involve known caspases or p53. Cancer Res 59:4848–4856PubMed Mathiasen IS, Lademann U, Jaattela M (1999) Apoptosis induced by vitamin D compounds in breast cancer is inhibited by Bcl-2 but doesn't involve known caspases or p53. Cancer Res 59:4848–4856PubMed
27.
go back to reference Miller GJ, Stapleton GE, Ferrara JA, Lucia MS, Pfister S et al (1992) The human prostatic carcinoma cell line LNCaP expresses biologically active, specific receptors for 1 alpha, 25-dihydroxyvitamin D3. Cancer Res 52:515–520PubMed Miller GJ, Stapleton GE, Ferrara JA, Lucia MS, Pfister S et al (1992) The human prostatic carcinoma cell line LNCaP expresses biologically active, specific receptors for 1 alpha, 25-dihydroxyvitamin D3. Cancer Res 52:515–520PubMed
28.
go back to reference Mork-Hansen C, Frandsen TL, Brunner N, Binderup L (1994) 1α-25-Dihydroxyvitamin D3 inhibits the invasive potential of human breast cancer cells in vitro. Clin. Exp. Metas. 12:195–202. doi:10.1007/BF01753887 CrossRef Mork-Hansen C, Frandsen TL, Brunner N, Binderup L (1994) 1α-25-Dihydroxyvitamin D3 inhibits the invasive potential of human breast cancer cells in vitro. Clin. Exp. Metas. 12:195–202. doi:10.​1007/​BF01753887 CrossRef
30.
go back to reference Chen S, Xue Y, Zhang X, Wu Y, Pan J, Wang Y, Ceng J (2005) A new human acute monocytic leukemia cell line SHI-1 with t(6;11)(q27;q23) gene alteration and high tumorigenicity in nude mice. Hematologia 90:766–775 Chen S, Xue Y, Zhang X, Wu Y, Pan J, Wang Y, Ceng J (2005) A new human acute monocytic leukemia cell line SHI-1 with t(6;11)(q27;q23) gene alteration and high tumorigenicity in nude mice. Hematologia 90:766–775
31.
go back to reference Park WH, Seol JG, Kim ES, Jung CW, Lee CC, Binderup L, Koeffler HP, Kim BK, Lee YY (2000) Cell cycle arrest induced by vitamin D3 analog EB1089 in NCI-H929 myeloma cells is associated with induction of the cyclin-dependent kinase inhibitor p27. Exp Cell Res 254:279–286. doi:10.1006/excr.1999.4735 CrossRefPubMed Park WH, Seol JG, Kim ES, Jung CW, Lee CC, Binderup L, Koeffler HP, Kim BK, Lee YY (2000) Cell cycle arrest induced by vitamin D3 analog EB1089 in NCI-H929 myeloma cells is associated with induction of the cyclin-dependent kinase inhibitor p27. Exp Cell Res 254:279–286. doi:10.​1006/​excr.​1999.​4735 CrossRefPubMed
36.
Metadata
Title
Treatment of K562 cells with 1,25-dihydroxyvitamin D3 induces distinct alterations in the expression of apoptosis-related genes BCL2, BAX, BCLXL, and p21
Authors
Sefa Kizildag
Halil Ates
Servet Kizildag
Publication date
01-01-2010
Publisher
Springer-Verlag
Published in
Annals of Hematology / Issue 1/2010
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-009-0766-y

Other articles of this Issue 1/2010

Annals of Hematology 1/2010 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine