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All-trans retinoic acid arrests cell cycle in leukemic bone marrow stromal cells by increasing intercellular communication through connexin 43-mediated gap junction.

Liu Y, Wen Q, Chen XL, Yang SJ, Gao L, Gao L, Zhang C, Li JL, Xiang XX, Wan K, Chen XH, Zhang X, Zhong JF - J Hematol Oncol (2015)

Bottom Line: Gap junctional intercellular communication (GJIC) is typically decreased in malignant tumors.Most of the observed effects mediated by ATRA were abolished by amphotericin-B pretreatment.ATRA arrests cell cycle progression in leukemic BMSCs, likely due to upregulating Cx43 expression and enhancing GJIC function.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, Xinqiao Hospital, the Third Military Medical University, Xinqiao Street, Chongqing, 400037, China. yl749@foxmail.com.

ABSTRACT

Background: Gap junctional intercellular communication (GJIC) is typically decreased in malignant tumors. Gap junction is not presented between hematopoietic cells but occurred in bone marrow stromal cells (BMSCs). Connexin 43 (Cx43) is the major gap junction (GJ) protein; our previous study revealed that Cx43 expression and GJIC were decreased in acute leukemic BMSCs. All-trans retinoic acid (ATRA) increases GJIC in a variety of cancer cells and has been used to treat acute promyelocytic leukemia, but the effects of ATRA on leukemic BMSCs is unknown. In this study, we evaluated the potential effects of ATRA on cell cycle, proliferation, and apoptosis of leukemic BMSCs. Effects of ATRA on Cx43 expression and GJIC were also examined.

Methods: Human BMSCs obtained from 25 patients with primary acute leukemia, and 10 normal healthy donors were cultured. Effects of ATRA on cell cycle, cell proliferation, and apoptosis were examined with or without co-treatment with amphotericin-B. Cx43 expression was examined at both the mRNA and protein expression levels. GJIC was examined by using a dye transfer assay and measuring the rate of fluorescence recovery after photobleaching (FRAP).

Results: ATRA arrested the cell cycle progression, inhibited cell growth, and increased apoptosis in leukemic BMSCs. Both Cx43 expression and GJIC function were increased by ATRA treatment. Most of the observed effects mediated by ATRA were abolished by amphotericin-B pretreatment.

Conclusions: ATRA arrests cell cycle progression in leukemic BMSCs, likely due to upregulating Cx43 expression and enhancing GJIC function.

No MeSH data available.


Related in: MedlinePlus

Effects of ATRA on the cell viability of BMSCs (MTT assay). Cell viability was evaluated by MTT assay in leukemic BMSCs, leukemic BMSCs treated with ATRA, and leukemic BMSCs treated with both ATRA and amphotericin-B. Data are presented as mean ± SD. Single asterisk indicates significant difference (P < 0.05)
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Fig5: Effects of ATRA on the cell viability of BMSCs (MTT assay). Cell viability was evaluated by MTT assay in leukemic BMSCs, leukemic BMSCs treated with ATRA, and leukemic BMSCs treated with both ATRA and amphotericin-B. Data are presented as mean ± SD. Single asterisk indicates significant difference (P < 0.05)

Mentions: ATRA (10 uM for 48 h) inhibited the cell growth of leukemic BMSCs by 40 % (p < 0.05; Fig. 5), and pretreatment with amphotericin-B blocked the ATRA effects.Fig. 5


All-trans retinoic acid arrests cell cycle in leukemic bone marrow stromal cells by increasing intercellular communication through connexin 43-mediated gap junction.

Liu Y, Wen Q, Chen XL, Yang SJ, Gao L, Gao L, Zhang C, Li JL, Xiang XX, Wan K, Chen XH, Zhang X, Zhong JF - J Hematol Oncol (2015)

Effects of ATRA on the cell viability of BMSCs (MTT assay). Cell viability was evaluated by MTT assay in leukemic BMSCs, leukemic BMSCs treated with ATRA, and leukemic BMSCs treated with both ATRA and amphotericin-B. Data are presented as mean ± SD. Single asterisk indicates significant difference (P < 0.05)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4597383&req=5

Fig5: Effects of ATRA on the cell viability of BMSCs (MTT assay). Cell viability was evaluated by MTT assay in leukemic BMSCs, leukemic BMSCs treated with ATRA, and leukemic BMSCs treated with both ATRA and amphotericin-B. Data are presented as mean ± SD. Single asterisk indicates significant difference (P < 0.05)
Mentions: ATRA (10 uM for 48 h) inhibited the cell growth of leukemic BMSCs by 40 % (p < 0.05; Fig. 5), and pretreatment with amphotericin-B blocked the ATRA effects.Fig. 5

Bottom Line: Gap junctional intercellular communication (GJIC) is typically decreased in malignant tumors.Most of the observed effects mediated by ATRA were abolished by amphotericin-B pretreatment.ATRA arrests cell cycle progression in leukemic BMSCs, likely due to upregulating Cx43 expression and enhancing GJIC function.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, Xinqiao Hospital, the Third Military Medical University, Xinqiao Street, Chongqing, 400037, China. yl749@foxmail.com.

ABSTRACT

Background: Gap junctional intercellular communication (GJIC) is typically decreased in malignant tumors. Gap junction is not presented between hematopoietic cells but occurred in bone marrow stromal cells (BMSCs). Connexin 43 (Cx43) is the major gap junction (GJ) protein; our previous study revealed that Cx43 expression and GJIC were decreased in acute leukemic BMSCs. All-trans retinoic acid (ATRA) increases GJIC in a variety of cancer cells and has been used to treat acute promyelocytic leukemia, but the effects of ATRA on leukemic BMSCs is unknown. In this study, we evaluated the potential effects of ATRA on cell cycle, proliferation, and apoptosis of leukemic BMSCs. Effects of ATRA on Cx43 expression and GJIC were also examined.

Methods: Human BMSCs obtained from 25 patients with primary acute leukemia, and 10 normal healthy donors were cultured. Effects of ATRA on cell cycle, cell proliferation, and apoptosis were examined with or without co-treatment with amphotericin-B. Cx43 expression was examined at both the mRNA and protein expression levels. GJIC was examined by using a dye transfer assay and measuring the rate of fluorescence recovery after photobleaching (FRAP).

Results: ATRA arrested the cell cycle progression, inhibited cell growth, and increased apoptosis in leukemic BMSCs. Both Cx43 expression and GJIC function were increased by ATRA treatment. Most of the observed effects mediated by ATRA were abolished by amphotericin-B pretreatment.

Conclusions: ATRA arrests cell cycle progression in leukemic BMSCs, likely due to upregulating Cx43 expression and enhancing GJIC function.

No MeSH data available.


Related in: MedlinePlus