Mahanine drives pancreatic adenocarcinoma cells into endoplasmic reticular stress-mediated apoptosis through modulating sialylation process and Ca2+-signaling
Endoplasmic reticulum (ER) stress results from protein unfolding/misfolding during cellular maturation, which requires a coordinated action of several chaperones and enzymes and Ca 2+ signalling. ER-stress possibly has a positive effect on survival of pancreatic cancer cell. Therefore, detailed insi...
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| Veröffentlicht in: | Scientific reports 2018-03, Vol.8 (1), p.1-12, Article 3911 |
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| creator | Sarkar Bhattacharya, Sayantani Mandal, Chandan Albiez, Reinhard Schwartz Samanta, Suman Kumar Mandal, Chitra |
| description | Endoplasmic reticulum (ER) stress results from protein unfolding/misfolding during cellular maturation, which requires a coordinated action of several chaperones and enzymes and Ca
2+
signalling. ER-stress possibly has a positive effect on survival of pancreatic cancer cell. Therefore, detailed insights into this complex signaling network are urgently needed. Here, we systematically analyzed the impact of ER stress-mediated unfolded protein response (UPR) and Ca
2+
-signaling cross-talk for the survival of pancreatic adenocarcinoma (PDAC) cells. We observed enhanced ER activity and initiation of UPR signaling induced by a carbazole alkaloid (mahanine). This event triggers a time-dependent increase of intracellular Ca
2+
leakage from ER and subsequently Ca
2+
signaling induced by enhanced reactive oxygen species (ROS) produced by this pro-oxidant agent. In addition, we observed an altered glycosylation, in particular with regard to reduced linkage-specific sialic acids possibly due to decreased sialyltransferase activity. Changes in sialylation entailed enhanced expression of the ganglioside GD3 in the treated cells. GD3, an inducer of apoptosis, inhibited pancreatic xenograft tumor. Taken together, our study describes a molecular scenario how PDAC cells are driven into apoptosis by mahanine by UPR-driven ER stress-associated and ROS-mediated calcium signaling and possibly defective sialylation. |
| doi_str_mv | 10.1038/s41598-018-22143-w |
| format | Article |
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2+
signalling. ER-stress possibly has a positive effect on survival of pancreatic cancer cell. Therefore, detailed insights into this complex signaling network are urgently needed. Here, we systematically analyzed the impact of ER stress-mediated unfolded protein response (UPR) and Ca
2+
-signaling cross-talk for the survival of pancreatic adenocarcinoma (PDAC) cells. We observed enhanced ER activity and initiation of UPR signaling induced by a carbazole alkaloid (mahanine). This event triggers a time-dependent increase of intracellular Ca
2+
leakage from ER and subsequently Ca
2+
signaling induced by enhanced reactive oxygen species (ROS) produced by this pro-oxidant agent. In addition, we observed an altered glycosylation, in particular with regard to reduced linkage-specific sialic acids possibly due to decreased sialyltransferase activity. Changes in sialylation entailed enhanced expression of the ganglioside GD3 in the treated cells. GD3, an inducer of apoptosis, inhibited pancreatic xenograft tumor. Taken together, our study describes a molecular scenario how PDAC cells are driven into apoptosis by mahanine by UPR-driven ER stress-associated and ROS-mediated calcium signaling and possibly defective sialylation.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-018-22143-w</identifier><identifier>PMID: 29500369</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>38 ; 38/61 ; 631/67/1504/1713 ; 631/80/86/2366 ; 82 ; 96 ; 96/1 ; 96/2 ; 96/31 ; Adenocarcinoma ; Apoptosis ; Calcium (intracellular) ; Calcium (reticular) ; Calcium signalling ; Carbazole ; Cell survival ; Chaperones ; Endoplasmic reticulum ; Glycosylation ; Humanities and Social Sciences ; Intracellular signalling ; multidisciplinary ; Oxidizing agents ; Pancreatic cancer ; Protein folding ; Reactive oxygen species ; Science ; Science (multidisciplinary) ; Sialic acids ; Xenografts</subject><ispartof>Scientific reports, 2018-03, Vol.8 (1), p.1-12, Article 3911</ispartof><rights>The Author(s) 2018</rights><rights>2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c381t-75e69895dbc8695e5db8ee98c120c81821b16d8fb8fc62bbf7498d6b55ced9423</citedby><cites>FETCH-LOGICAL-c381t-75e69895dbc8695e5db8ee98c120c81821b16d8fb8fc62bbf7498d6b55ced9423</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834441/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834441/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids></links><search><creatorcontrib>Sarkar Bhattacharya, Sayantani</creatorcontrib><creatorcontrib>Mandal, Chandan</creatorcontrib><creatorcontrib>Albiez, Reinhard Schwartz</creatorcontrib><creatorcontrib>Samanta, Suman Kumar</creatorcontrib><creatorcontrib>Mandal, Chitra</creatorcontrib><title>Mahanine drives pancreatic adenocarcinoma cells into endoplasmic reticular stress-mediated apoptosis through modulating sialylation process and Ca2+-signaling</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><description>Endoplasmic reticulum (ER) stress results from protein unfolding/misfolding during cellular maturation, which requires a coordinated action of several chaperones and enzymes and Ca
2+
signalling. ER-stress possibly has a positive effect on survival of pancreatic cancer cell. Therefore, detailed insights into this complex signaling network are urgently needed. Here, we systematically analyzed the impact of ER stress-mediated unfolded protein response (UPR) and Ca
2+
-signaling cross-talk for the survival of pancreatic adenocarcinoma (PDAC) cells. We observed enhanced ER activity and initiation of UPR signaling induced by a carbazole alkaloid (mahanine). This event triggers a time-dependent increase of intracellular Ca
2+
leakage from ER and subsequently Ca
2+
signaling induced by enhanced reactive oxygen species (ROS) produced by this pro-oxidant agent. In addition, we observed an altered glycosylation, in particular with regard to reduced linkage-specific sialic acids possibly due to decreased sialyltransferase activity. Changes in sialylation entailed enhanced expression of the ganglioside GD3 in the treated cells. GD3, an inducer of apoptosis, inhibited pancreatic xenograft tumor. Taken together, our study describes a molecular scenario how PDAC cells are driven into apoptosis by mahanine by UPR-driven ER stress-associated and ROS-mediated calcium signaling and possibly defective sialylation.</description><subject>38</subject><subject>38/61</subject><subject>631/67/1504/1713</subject><subject>631/80/86/2366</subject><subject>82</subject><subject>96</subject><subject>96/1</subject><subject>96/2</subject><subject>96/31</subject><subject>Adenocarcinoma</subject><subject>Apoptosis</subject><subject>Calcium (intracellular)</subject><subject>Calcium (reticular)</subject><subject>Calcium signalling</subject><subject>Carbazole</subject><subject>Cell survival</subject><subject>Chaperones</subject><subject>Endoplasmic reticulum</subject><subject>Glycosylation</subject><subject>Humanities and Social Sciences</subject><subject>Intracellular signalling</subject><subject>multidisciplinary</subject><subject>Oxidizing agents</subject><subject>Pancreatic cancer</subject><subject>Protein folding</subject><subject>Reactive oxygen species</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Sialic acids</subject><subject>Xenografts</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kkuLFDEUhQtRnGGcP-Aq4EaQ0iT16GQjSOMLRtzoOtxKblVnqErK3NQM82f8rabtwdfCbHIg3zncJKeqngr-UvBGvaJWdFrVXKhaStE29e2D6lzytqtlI-XDP_RZdUl0zcvqpG6FflydSd1x3vT6vPr-CQ4QfEDmkr9BYisEmxCytwwchmghWR_iAsziPBPzIUeGwcV1BloKlbCw2wyJUU5IVC_oPGR0DNa45kieWD6kuE0HtkRXyOzDxMjDfHfUMbA1RVucDIJje5AvavJTgLlgT6pHI8yEl_f7RfX13dsv-w_11ef3H_dvrmrbKJHrXYe9Vrpzg1W97rAIhaiVFZJbJZQUg-idGgc12l4Ow7hrtXL90HUWnW5lc1G9PuWu21DmtxhygtmsyS-Q7kwEb_4-Cf5gpnhjOtW0bStKwPP7gBS_bUjZLJ6OLwYB40ZG8vJrO1nogj77B72OWyr3PVJcq91OyaZQ8kTZFIkSjr-GEdwcG2BODTClAeZnA8xtMTUnExU4TJh-R__H9QPlfrgw</recordid><startdate>20180302</startdate><enddate>20180302</enddate><creator>Sarkar Bhattacharya, Sayantani</creator><creator>Mandal, Chandan</creator><creator>Albiez, Reinhard Schwartz</creator><creator>Samanta, Suman Kumar</creator><creator>Mandal, Chitra</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20180302</creationdate><title>Mahanine drives pancreatic adenocarcinoma cells into endoplasmic reticular stress-mediated apoptosis through modulating sialylation process and Ca2+-signaling</title><author>Sarkar Bhattacharya, Sayantani ; Mandal, Chandan ; Albiez, Reinhard Schwartz ; Samanta, Suman Kumar ; Mandal, Chitra</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-75e69895dbc8695e5db8ee98c120c81821b16d8fb8fc62bbf7498d6b55ced9423</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>38</topic><topic>38/61</topic><topic>631/67/1504/1713</topic><topic>631/80/86/2366</topic><topic>82</topic><topic>96</topic><topic>96/1</topic><topic>96/2</topic><topic>96/31</topic><topic>Adenocarcinoma</topic><topic>Apoptosis</topic><topic>Calcium (intracellular)</topic><topic>Calcium (reticular)</topic><topic>Calcium signalling</topic><topic>Carbazole</topic><topic>Cell survival</topic><topic>Chaperones</topic><topic>Endoplasmic reticulum</topic><topic>Glycosylation</topic><topic>Humanities and Social Sciences</topic><topic>Intracellular signalling</topic><topic>multidisciplinary</topic><topic>Oxidizing agents</topic><topic>Pancreatic cancer</topic><topic>Protein folding</topic><topic>Reactive oxygen species</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Sialic acids</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sarkar Bhattacharya, Sayantani</creatorcontrib><creatorcontrib>Mandal, Chandan</creatorcontrib><creatorcontrib>Albiez, Reinhard Schwartz</creatorcontrib><creatorcontrib>Samanta, Suman Kumar</creatorcontrib><creatorcontrib>Mandal, Chitra</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sarkar Bhattacharya, Sayantani</au><au>Mandal, Chandan</au><au>Albiez, Reinhard Schwartz</au><au>Samanta, Suman Kumar</au><au>Mandal, Chitra</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mahanine drives pancreatic adenocarcinoma cells into endoplasmic reticular stress-mediated apoptosis through modulating sialylation process and Ca2+-signaling</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><date>2018-03-02</date><risdate>2018</risdate><volume>8</volume><issue>1</issue><spage>1</spage><epage>12</epage><pages>1-12</pages><artnum>3911</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Endoplasmic reticulum (ER) stress results from protein unfolding/misfolding during cellular maturation, which requires a coordinated action of several chaperones and enzymes and Ca
2+
signalling. ER-stress possibly has a positive effect on survival of pancreatic cancer cell. Therefore, detailed insights into this complex signaling network are urgently needed. Here, we systematically analyzed the impact of ER stress-mediated unfolded protein response (UPR) and Ca
2+
-signaling cross-talk for the survival of pancreatic adenocarcinoma (PDAC) cells. We observed enhanced ER activity and initiation of UPR signaling induced by a carbazole alkaloid (mahanine). This event triggers a time-dependent increase of intracellular Ca
2+
leakage from ER and subsequently Ca
2+
signaling induced by enhanced reactive oxygen species (ROS) produced by this pro-oxidant agent. In addition, we observed an altered glycosylation, in particular with regard to reduced linkage-specific sialic acids possibly due to decreased sialyltransferase activity. Changes in sialylation entailed enhanced expression of the ganglioside GD3 in the treated cells. GD3, an inducer of apoptosis, inhibited pancreatic xenograft tumor. Taken together, our study describes a molecular scenario how PDAC cells are driven into apoptosis by mahanine by UPR-driven ER stress-associated and ROS-mediated calcium signaling and possibly defective sialylation.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>29500369</pmid><doi>10.1038/s41598-018-22143-w</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 38 38/61 631/67/1504/1713 631/80/86/2366 82 96 96/1 96/2 96/31 Adenocarcinoma Apoptosis Calcium (intracellular) Calcium (reticular) Calcium signalling Carbazole Cell survival Chaperones Endoplasmic reticulum Glycosylation Humanities and Social Sciences Intracellular signalling multidisciplinary Oxidizing agents Pancreatic cancer Protein folding Reactive oxygen species Science Science (multidisciplinary) Sialic acids Xenografts |
| title | Mahanine drives pancreatic adenocarcinoma cells into endoplasmic reticular stress-mediated apoptosis through modulating sialylation process and Ca2+-signaling |
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