Downregulation of hTERT: an important As2O3 induced mechanism of apoptosis in myelodysplastic syndrome.
Two myelodysplastic syndrome (MDS) cell lines, MUTZ-1 and SKM-1 cells, were used to study the effect of arsenic trioxide (As2O3) on hematological malignant cells. As2O3 induced this two cell lines apoptosis via activation of caspase-3/8 and cleavage of poly (ADP-ribose) polymerase (PARP), a DNA repa...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0113199&type=printable |
| _version_ | 1826587280003825664 |
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| author | Weilai Xu Yungui Wang Hongyan Tong Wenbin Qian Jie Jin |
| author_facet | Weilai Xu Yungui Wang Hongyan Tong Wenbin Qian Jie Jin |
| author_sort | Weilai Xu |
| collection | DOAJ |
| description | Two myelodysplastic syndrome (MDS) cell lines, MUTZ-1 and SKM-1 cells, were used to study the effect of arsenic trioxide (As2O3) on hematological malignant cells. As2O3 induced this two cell lines apoptosis via activation of caspase-3/8 and cleavage of poly (ADP-ribose) polymerase (PARP), a DNA repair enzyme. As2O3 reduced NF-κB activity, which was important for inducing MUTZ-1 and SKM-1 cells apoptosis. As2O3 also inhibited the activities of hTERT in MUTZ-1 and SKM-1 cells. Moreover, the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), had no effect on caspase-8 activation, although PDTC did inhibit MUTZ-1 and SKM-1 cells proliferation. Incubation of MUTZ-1 cells with a caspase-8 inhibitor failed to block As2O3-induced inhibition of NF-κB activity. Our findings suggest that As2O3 may induce apoptosis in MUTZ-1 and SKM-1 cells by two independent pathways: first, by activation of caspase-3/8 and PARP; and second, by inhibition of NF-κB activity, which results in downregulation of hTERT expression. We conclude that hTERT and NF-κB are important molecular targets in As2O3-induced apoptosis. |
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| issn | 1932-6203 |
| language | English |
| last_indexed | 2025-03-14T16:22:55Z |
| publishDate | 2014-01-01 |
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| spelling | doaj.art-3fc66043a1994bf9bad6458e1a65360b2025-02-22T05:32:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01911e11319910.1371/journal.pone.0113199Downregulation of hTERT: an important As2O3 induced mechanism of apoptosis in myelodysplastic syndrome.Weilai XuYungui WangHongyan TongWenbin QianJie JinTwo myelodysplastic syndrome (MDS) cell lines, MUTZ-1 and SKM-1 cells, were used to study the effect of arsenic trioxide (As2O3) on hematological malignant cells. As2O3 induced this two cell lines apoptosis via activation of caspase-3/8 and cleavage of poly (ADP-ribose) polymerase (PARP), a DNA repair enzyme. As2O3 reduced NF-κB activity, which was important for inducing MUTZ-1 and SKM-1 cells apoptosis. As2O3 also inhibited the activities of hTERT in MUTZ-1 and SKM-1 cells. Moreover, the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), had no effect on caspase-8 activation, although PDTC did inhibit MUTZ-1 and SKM-1 cells proliferation. Incubation of MUTZ-1 cells with a caspase-8 inhibitor failed to block As2O3-induced inhibition of NF-κB activity. Our findings suggest that As2O3 may induce apoptosis in MUTZ-1 and SKM-1 cells by two independent pathways: first, by activation of caspase-3/8 and PARP; and second, by inhibition of NF-κB activity, which results in downregulation of hTERT expression. We conclude that hTERT and NF-κB are important molecular targets in As2O3-induced apoptosis.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0113199&type=printable |
| spellingShingle | Weilai Xu Yungui Wang Hongyan Tong Wenbin Qian Jie Jin Downregulation of hTERT: an important As2O3 induced mechanism of apoptosis in myelodysplastic syndrome. PLoS ONE |
| title | Downregulation of hTERT: an important As2O3 induced mechanism of apoptosis in myelodysplastic syndrome. |
| title_full | Downregulation of hTERT: an important As2O3 induced mechanism of apoptosis in myelodysplastic syndrome. |
| title_fullStr | Downregulation of hTERT: an important As2O3 induced mechanism of apoptosis in myelodysplastic syndrome. |
| title_full_unstemmed | Downregulation of hTERT: an important As2O3 induced mechanism of apoptosis in myelodysplastic syndrome. |
| title_short | Downregulation of hTERT: an important As2O3 induced mechanism of apoptosis in myelodysplastic syndrome. |
| title_sort | downregulation of htert an important as2o3 induced mechanism of apoptosis in myelodysplastic syndrome |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0113199&type=printable |
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