PIM inhibitor SMI-4a induces cell apoptosis in B-cell acute lymphocytic leukemia cells via the HO-1-mediated JAK2/STAT3 pathway
The serine/threonine PIM protein kinases are critical regulators of tumorigenesis in multiple cancers. However, whether PIMs are potential therapeutic targets for treating B-cell acute lymphocytic leukemia (B-ALL) remains unclear. Therefore, here, PIM expression was detected in B-ALL patients and th...
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Veröffentlicht in: | Life sciences (1973) 2019-02, Vol.219, p.248-256 |
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creator | Kuang, Xingyi Xiong, Jie Wang, Weili Li, Xinyao Lu, Tingting Fang, Qin Wang, Jishi |
description | The serine/threonine PIM protein kinases are critical regulators of tumorigenesis in multiple cancers. However, whether PIMs are potential therapeutic targets for treating B-cell acute lymphocytic leukemia (B-ALL) remains unclear. Therefore, here, PIM expression was detected in B-ALL patients and the effects of SMI-4a, a pan-PIM small molecule inhibitor, were investigated in B-ALL cells.
PIM1 and PIM2 expression in 26 newly diagnosed B-ALL cases was detected by real-time PCR and Western blot. B-ALL cells were treated with varied SMI-4a doses and the viability of treated cells was investigated using a cell-counting kit-8 (CCK-8) assay. Apoptosis and cell cycles were analyzed by flow cytometry. Western blot analysis was then used to explore the expression of apoptosis-related proteins and the JAK2/STAT3 pathway.
PIM1 and 2 were overexpressed in B-ALL patients with high HO-1 level. SMI-4a induced decreases in PIMs and HO-1 expressions and inhibited B-ALL cell viability. Treatment with SMI-4a induced apoptosis by downregulating Bcl-2, upregulating Bax and other antiapoptotic proteins, and decreasing protein levels of p-JAK2 and p-STAT3. In addition, upregulation of HO-1 alleviated decrease in p-JAK2 and p-STAT3 expression, reduced SMI-4a-induced apoptosis of B-ALL cells, and influenced B-ALL cell survival.
PIMs were highly expressed in B-ALL patients. SMI-4a inhibited B-ALL proliferation and induced apoptosis via the HO-1-mediated JAK2/STAT3 pathway. SMI-4a might be applicable for treatment of B-ALL cells. |
doi_str_mv | 10.1016/j.lfs.2019.01.022 |
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PIM1 and PIM2 expression in 26 newly diagnosed B-ALL cases was detected by real-time PCR and Western blot. B-ALL cells were treated with varied SMI-4a doses and the viability of treated cells was investigated using a cell-counting kit-8 (CCK-8) assay. Apoptosis and cell cycles were analyzed by flow cytometry. Western blot analysis was then used to explore the expression of apoptosis-related proteins and the JAK2/STAT3 pathway.
PIM1 and 2 were overexpressed in B-ALL patients with high HO-1 level. SMI-4a induced decreases in PIMs and HO-1 expressions and inhibited B-ALL cell viability. Treatment with SMI-4a induced apoptosis by downregulating Bcl-2, upregulating Bax and other antiapoptotic proteins, and decreasing protein levels of p-JAK2 and p-STAT3. In addition, upregulation of HO-1 alleviated decrease in p-JAK2 and p-STAT3 expression, reduced SMI-4a-induced apoptosis of B-ALL cells, and influenced B-ALL cell survival.
PIMs were highly expressed in B-ALL patients. SMI-4a inhibited B-ALL proliferation and induced apoptosis via the HO-1-mediated JAK2/STAT3 pathway. SMI-4a might be applicable for treatment of B-ALL cells.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/j.lfs.2019.01.022</identifier><identifier>PMID: 30658101</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Apoptosis ; B-ALL ; JAK2/STAT3 ; SMI-4a</subject><ispartof>Life sciences (1973), 2019-02, Vol.219, p.248-256</ispartof><rights>2019</rights><rights>Copyright © 2019. Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-d9346abf950cb6b0ed957830a609287febf14833d803f38e7f4544fc7bb04993</citedby><cites>FETCH-LOGICAL-c353t-d9346abf950cb6b0ed957830a609287febf14833d803f38e7f4544fc7bb04993</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0024320519300311$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30658101$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kuang, Xingyi</creatorcontrib><creatorcontrib>Xiong, Jie</creatorcontrib><creatorcontrib>Wang, Weili</creatorcontrib><creatorcontrib>Li, Xinyao</creatorcontrib><creatorcontrib>Lu, Tingting</creatorcontrib><creatorcontrib>Fang, Qin</creatorcontrib><creatorcontrib>Wang, Jishi</creatorcontrib><title>PIM inhibitor SMI-4a induces cell apoptosis in B-cell acute lymphocytic leukemia cells via the HO-1-mediated JAK2/STAT3 pathway</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>The serine/threonine PIM protein kinases are critical regulators of tumorigenesis in multiple cancers. However, whether PIMs are potential therapeutic targets for treating B-cell acute lymphocytic leukemia (B-ALL) remains unclear. Therefore, here, PIM expression was detected in B-ALL patients and the effects of SMI-4a, a pan-PIM small molecule inhibitor, were investigated in B-ALL cells.
PIM1 and PIM2 expression in 26 newly diagnosed B-ALL cases was detected by real-time PCR and Western blot. B-ALL cells were treated with varied SMI-4a doses and the viability of treated cells was investigated using a cell-counting kit-8 (CCK-8) assay. Apoptosis and cell cycles were analyzed by flow cytometry. Western blot analysis was then used to explore the expression of apoptosis-related proteins and the JAK2/STAT3 pathway.
PIM1 and 2 were overexpressed in B-ALL patients with high HO-1 level. SMI-4a induced decreases in PIMs and HO-1 expressions and inhibited B-ALL cell viability. Treatment with SMI-4a induced apoptosis by downregulating Bcl-2, upregulating Bax and other antiapoptotic proteins, and decreasing protein levels of p-JAK2 and p-STAT3. In addition, upregulation of HO-1 alleviated decrease in p-JAK2 and p-STAT3 expression, reduced SMI-4a-induced apoptosis of B-ALL cells, and influenced B-ALL cell survival.
PIMs were highly expressed in B-ALL patients. SMI-4a inhibited B-ALL proliferation and induced apoptosis via the HO-1-mediated JAK2/STAT3 pathway. SMI-4a might be applicable for treatment of B-ALL cells.</description><subject>Apoptosis</subject><subject>B-ALL</subject><subject>JAK2/STAT3</subject><subject>SMI-4a</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kM1v1DAQxS1ERbeFP4AL8pFL0vFHPixOS1Xapa2K1L1bjjPWekk2IXaK9tR_vV62cOQ0o6f3nmZ-hHxkkDNg5cU271zIOTCVA8uB8zdkwepKZVAK9pYsALjMBIfilJyFsAWAoqjEO3IqoCzqVLEgzz9W99TvNr7xcZjo4_0qkyYJ7WwxUItdR804jHEIPiSZfs2Omp0j0m7fj5vB7qO3tMP5J_be_MkE-pS2uEF685CxrMfWm4gt_b685ReP6-Va0NHEzW-zf09OnOkCfnid52T97Wp9eZPdPVyvLpd3mRWFiFmrhCxN41QBtikbwFYVVS3AlKB4XTlsHJO1EG0NwokaKycLKZ2tmgakUuKcfD7WjtPwa8YQde_D4VKzw2EOmrNKiVJyWSQrO1rtNIQwodPj5Hsz7TUDfcCutzph1wfsGphO2FPm02v93KRn_yX-ck6GL0cDph-fPE46WI87m8BMaKNuB_-f-hfBlpFm</recordid><startdate>20190215</startdate><enddate>20190215</enddate><creator>Kuang, Xingyi</creator><creator>Xiong, Jie</creator><creator>Wang, Weili</creator><creator>Li, Xinyao</creator><creator>Lu, Tingting</creator><creator>Fang, Qin</creator><creator>Wang, Jishi</creator><general>Elsevier Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20190215</creationdate><title>PIM inhibitor SMI-4a induces cell apoptosis in B-cell acute lymphocytic leukemia cells via the HO-1-mediated JAK2/STAT3 pathway</title><author>Kuang, Xingyi ; Xiong, Jie ; Wang, Weili ; Li, Xinyao ; Lu, Tingting ; Fang, Qin ; Wang, Jishi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-d9346abf950cb6b0ed957830a609287febf14833d803f38e7f4544fc7bb04993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Apoptosis</topic><topic>B-ALL</topic><topic>JAK2/STAT3</topic><topic>SMI-4a</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kuang, Xingyi</creatorcontrib><creatorcontrib>Xiong, Jie</creatorcontrib><creatorcontrib>Wang, Weili</creatorcontrib><creatorcontrib>Li, Xinyao</creatorcontrib><creatorcontrib>Lu, Tingting</creatorcontrib><creatorcontrib>Fang, Qin</creatorcontrib><creatorcontrib>Wang, Jishi</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kuang, Xingyi</au><au>Xiong, Jie</au><au>Wang, Weili</au><au>Li, Xinyao</au><au>Lu, Tingting</au><au>Fang, Qin</au><au>Wang, Jishi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PIM inhibitor SMI-4a induces cell apoptosis in B-cell acute lymphocytic leukemia cells via the HO-1-mediated JAK2/STAT3 pathway</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>2019-02-15</date><risdate>2019</risdate><volume>219</volume><spage>248</spage><epage>256</epage><pages>248-256</pages><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>The serine/threonine PIM protein kinases are critical regulators of tumorigenesis in multiple cancers. However, whether PIMs are potential therapeutic targets for treating B-cell acute lymphocytic leukemia (B-ALL) remains unclear. Therefore, here, PIM expression was detected in B-ALL patients and the effects of SMI-4a, a pan-PIM small molecule inhibitor, were investigated in B-ALL cells.
PIM1 and PIM2 expression in 26 newly diagnosed B-ALL cases was detected by real-time PCR and Western blot. B-ALL cells were treated with varied SMI-4a doses and the viability of treated cells was investigated using a cell-counting kit-8 (CCK-8) assay. Apoptosis and cell cycles were analyzed by flow cytometry. Western blot analysis was then used to explore the expression of apoptosis-related proteins and the JAK2/STAT3 pathway.
PIM1 and 2 were overexpressed in B-ALL patients with high HO-1 level. SMI-4a induced decreases in PIMs and HO-1 expressions and inhibited B-ALL cell viability. Treatment with SMI-4a induced apoptosis by downregulating Bcl-2, upregulating Bax and other antiapoptotic proteins, and decreasing protein levels of p-JAK2 and p-STAT3. In addition, upregulation of HO-1 alleviated decrease in p-JAK2 and p-STAT3 expression, reduced SMI-4a-induced apoptosis of B-ALL cells, and influenced B-ALL cell survival.
PIMs were highly expressed in B-ALL patients. SMI-4a inhibited B-ALL proliferation and induced apoptosis via the HO-1-mediated JAK2/STAT3 pathway. SMI-4a might be applicable for treatment of B-ALL cells.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>30658101</pmid><doi>10.1016/j.lfs.2019.01.022</doi><tpages>9</tpages></addata></record> |
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subjects | Apoptosis B-ALL JAK2/STAT3 SMI-4a |
title | PIM inhibitor SMI-4a induces cell apoptosis in B-cell acute lymphocytic leukemia cells via the HO-1-mediated JAK2/STAT3 pathway |
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