{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T23:46:11Z","timestamp":1784072771588,"version":"3.55.0"},"reference-count":68,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,10,3]],"date-time":"2018-10-03T00:00:00Z","timestamp":1538524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["102-2320-B-259-001-3"],"award-info":[{"award-number":["102-2320-B-259-001-3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Prodigiosin (PG) belongs to a family of prodiginines isolated from gram-negative bacteria. It is a water insoluble red pigment and a potent proapoptotic compound. This study elucidates the anti-tumor activity and underlying mechanism of PG in doxorubicin-sensitive (Dox-S) and doxorubicin-resistant (Dox-R) lung cancer cells. The cytotoxicity and cell death characteristics of PG in two cells were measured by MTT assay, cell cycle analysis, and apoptosis\/autophagic marker analysis. Then, the potential mechanism of PG-induced cell death was evaluated through the phosphatidylinositol-4,5-bisphosphate 3-kinase-p85\/Protein kinase B \/mammalian target of rapamycin (PI3K-p85\/Akt\/mTOR) and Beclin-1\/phosphatidylinositol-4,5-bisphosphate 3-kinase-Class III (Beclin-1\/PI3K-Class III) signaling. Finally, in vivo efficacy was examined by intratracheal inoculation and treatment. There was similar cytotoxicity with PG in both Dox-S and Dox-R cells, where the half maximal inhibitory concentrations (IC50) were all in 10 \u03bcM. Based on a non-significant increase in the sub-G1 phase with an increase of microtubule-associated proteins 1A\/1B light chain 3B-phosphatidylethanolamine conjugate (LC3-II), the cell death of both cells was categorized to achieve autophagy. Interestingly, an increase in cleaved-poly ADP ribose polymerase (cleaved-PARP) also showed the existence of an apoptosis-sensitive subpopulation. In both Dox-S and Dox-R cells, PI3K-p85\/Akt\/mTOR signaling pathways were reduced, which inhibited autophagy initiation. However, Beclin-1\/PI3K-Class III downregulation implicated non-canonical autophagy pathways were involved in PG-induced autophagy. At completion of the PG regimen, tumors accumulated in the mice trachea and were attenuated by PG treatment, which indicated the efficacy of PG for both Dox-S and Dox-R lung cancer. All the above results concluded that PG is a potential chemotherapeutic agent for lung cancer regimens regardless of doxorubicin resistance.<\/jats:p>","DOI":"10.3390\/jcm7100321","type":"journal-article","created":{"date-parts":[[2018,10,4]],"date-time":"2018-10-04T02:19:49Z","timestamp":1538619589000},"page":"321","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Prodigiosin-Emerged PI3K\/Beclin-1-Independent Pathway Elicits Autophagic Cell Death in Doxorubicin-Sensitive and -Resistant Lung Cancer"],"prefix":"10.3390","volume":"7","author":[{"given":"Wei-Jun","family":"Chiu","sequence":"first","affiliation":[{"name":"Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 97401, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4160-2361","authenticated-orcid":false,"given":"Shian-Ren","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 97401, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hsin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 97401, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May-Jwan","family":"Tsai","sequence":"additional","affiliation":[{"name":"Neural Regeneration Laboratory, Neurological Institute, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6927-1517","authenticated-orcid":false,"given":"Max","family":"Leong","sequence":"additional","affiliation":[{"name":"Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 97401, Taiwan"},{"name":"Department of Chemistry, National Dong Hwa University, Hualien 97401, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Feng","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 97401, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21442","article-title":"Cancer statistics, 2018","volume":"68","author":"Siegel","year":"2018","journal-title":"CA Cancer J. 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