Cytotoxic properties of unfractionated and fractionated bromelain alone or in combination with chemotherapeutic agents in colorectal cancer cells
Colorectal cancer (CRC) is one of the most lethal cancers worldwide. Long-term survival is not achieved in metastatic CRC despite the current multidisciplinary therapies. Bromelain, a compound extracted from the pineapple plant, has multiple functions and anticancer properties. Previously, bromelain...
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| Veröffentlicht in: | PloS one 2023-06, Vol.18 (6), p.e0285970-e0285970 |
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| description | Colorectal cancer (CRC) is one of the most lethal cancers worldwide. Long-term survival is not achieved in metastatic CRC despite the current multidisciplinary therapies. Bromelain, a compound extracted from the pineapple plant, has multiple functions and anticancer properties. Previously, bromelain has been chromatographically separated into four fractions. Fraction 3 (F3) exhibits the highest proteolytic activity. The anticancer effects of F3 bromelain in CRC cells is unknown.
In vitro cytotoxicity was verified through a sulforhodamine B assay. Apoptosis in CRC cells induced by unfractionated or F3 bromelain was examined using Annexin V-FITC/PI staining and Western blot analysis. ROS status, autophagy and lysosome formation were determined by specific detection kit.
The cytotoxicity of F3 bromelain in CRC cells was found to be comparable to that of unfractionated bromelain. F3 bromelain induces caspase-dependent apoptosis in CRC cells. Treatment with unfractionated or F3 bromelain increased superoxide and oxidative stress levels and autophagy and lysosome formation. ATG5/12 and beclin-1 were upregulated, and the conversion of LC3B-I to LC3B-II was increased significantly by treatment with F3 bromelain. Treated CQ, autophagy inhibitor, with unfractionated or F3 bromelain enhances the cytotoxic effects. Finally, the combination of unfractionated and F3 bromelain with a routine chemotherapeutic agent (5-fluourouracil, irinotecan, or oxaliplatin) resulted in synergistically higher cytotoxic potency in CRC cells.
Unfractionated and F3 bromelain inhibits CRC cell proliferation in vitro, and the cytotoxic effects of unfractionated bromelain are equivalent to F3 bromelain. F3 bromelain may be a potential and potent drug for clinical use due to its anticancer efficacy and high synergistic cytotoxicity when combined with a routine chemotherapeutic agent for CRC. |
| doi_str_mv | 10.1371/journal.pone.0285970 |
| format | Article |
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In vitro cytotoxicity was verified through a sulforhodamine B assay. Apoptosis in CRC cells induced by unfractionated or F3 bromelain was examined using Annexin V-FITC/PI staining and Western blot analysis. ROS status, autophagy and lysosome formation were determined by specific detection kit.
The cytotoxicity of F3 bromelain in CRC cells was found to be comparable to that of unfractionated bromelain. F3 bromelain induces caspase-dependent apoptosis in CRC cells. Treatment with unfractionated or F3 bromelain increased superoxide and oxidative stress levels and autophagy and lysosome formation. ATG5/12 and beclin-1 were upregulated, and the conversion of LC3B-I to LC3B-II was increased significantly by treatment with F3 bromelain. Treated CQ, autophagy inhibitor, with unfractionated or F3 bromelain enhances the cytotoxic effects. Finally, the combination of unfractionated and F3 bromelain with a routine chemotherapeutic agent (5-fluourouracil, irinotecan, or oxaliplatin) resulted in synergistically higher cytotoxic potency in CRC cells.
Unfractionated and F3 bromelain inhibits CRC cell proliferation in vitro, and the cytotoxic effects of unfractionated bromelain are equivalent to F3 bromelain. F3 bromelain may be a potential and potent drug for clinical use due to its anticancer efficacy and high synergistic cytotoxicity when combined with a routine chemotherapeutic agent for CRC.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0285970</identifier><identifier>PMID: 37262048</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Annexin V ; Anticancer properties ; Antimitotic agents ; Antineoplastic agents ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Apoptosis ; Autophagy ; Biology and Life Sciences ; Bromelains - pharmacology ; Cancer ; Cancer therapies ; Care and treatment ; Caspase ; Cell cycle ; Cell death ; Cell Line, Tumor ; Cell Proliferation ; Chemotherapy ; Chromatography ; Colonic Neoplasms - drug therapy ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - pathology ; Cytotoxicity ; Diagnosis ; Dosage and administration ; Dyes ; Humans ; In vitro methods and tests ; Irinotecan ; Irinotecan - therapeutic use ; Medicine and Health Sciences ; Metastases ; Metastasis ; Oxaliplatin ; Oxidative stress ; Patient outcomes ; Physical Sciences ; Plant extracts ; Polymerase chain reaction ; Prevention ; Proteins ; Proteolysis ; Reagents ; Risk factors ; Sodium ; Sulforhodamine ; Superoxide ; Survival ; Thermal cycling ; Toxicity</subject><ispartof>PloS one, 2023-06, Vol.18 (6), p.e0285970-e0285970</ispartof><rights>Copyright: © 2023 Tsai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2023 Public Library of Science</rights><rights>2023 Tsai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 Tsai et al 2023 Tsai et al</rights><rights>2023 Tsai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Long-term survival is not achieved in metastatic CRC despite the current multidisciplinary therapies. Bromelain, a compound extracted from the pineapple plant, has multiple functions and anticancer properties. Previously, bromelain has been chromatographically separated into four fractions. Fraction 3 (F3) exhibits the highest proteolytic activity. The anticancer effects of F3 bromelain in CRC cells is unknown.
In vitro cytotoxicity was verified through a sulforhodamine B assay. Apoptosis in CRC cells induced by unfractionated or F3 bromelain was examined using Annexin V-FITC/PI staining and Western blot analysis. ROS status, autophagy and lysosome formation were determined by specific detection kit.
The cytotoxicity of F3 bromelain in CRC cells was found to be comparable to that of unfractionated bromelain. F3 bromelain induces caspase-dependent apoptosis in CRC cells. Treatment with unfractionated or F3 bromelain increased superoxide and oxidative stress levels and autophagy and lysosome formation. ATG5/12 and beclin-1 were upregulated, and the conversion of LC3B-I to LC3B-II was increased significantly by treatment with F3 bromelain. Treated CQ, autophagy inhibitor, with unfractionated or F3 bromelain enhances the cytotoxic effects. Finally, the combination of unfractionated and F3 bromelain with a routine chemotherapeutic agent (5-fluourouracil, irinotecan, or oxaliplatin) resulted in synergistically higher cytotoxic potency in CRC cells.
Unfractionated and F3 bromelain inhibits CRC cell proliferation in vitro, and the cytotoxic effects of unfractionated bromelain are equivalent to F3 bromelain. F3 bromelain may be a potential and potent drug for clinical use due to its anticancer efficacy and high synergistic cytotoxicity when combined with a routine chemotherapeutic agent for CRC.</description><subject>Analysis</subject><subject>Annexin V</subject><subject>Anticancer properties</subject><subject>Antimitotic agents</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Apoptosis</subject><subject>Autophagy</subject><subject>Biology and Life Sciences</subject><subject>Bromelains - pharmacology</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Caspase</subject><subject>Cell cycle</subject><subject>Cell death</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Chemotherapy</subject><subject>Chromatography</subject><subject>Colonic Neoplasms - drug 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properties of unfractionated and fractionated bromelain alone or in combination with chemotherapeutic agents in colorectal cancer cells</title><author>Tsai, Kuei-Yen ; Wei, Po-Li ; Azarkan, Mohamed ; M'Rabet, Nasiha ; Makondi, Precious Takondwa ; Chen, Hsin-An ; Huang, Chien-Yu ; Chang, Yu-Jia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c693t-88a1e92bf1d5aeb0bac6bf323a68d0433be4cad6b1c5aee8e8cdd0c59aff2ab23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Analysis</topic><topic>Annexin V</topic><topic>Anticancer properties</topic><topic>Antimitotic agents</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Apoptosis</topic><topic>Autophagy</topic><topic>Biology and Life Sciences</topic><topic>Bromelains - pharmacology</topic><topic>Cancer</topic><topic>Cancer 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One</addtitle><date>2023-06-01</date><risdate>2023</risdate><volume>18</volume><issue>6</issue><spage>e0285970</spage><epage>e0285970</epage><pages>e0285970-e0285970</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Colorectal cancer (CRC) is one of the most lethal cancers worldwide. Long-term survival is not achieved in metastatic CRC despite the current multidisciplinary therapies. Bromelain, a compound extracted from the pineapple plant, has multiple functions and anticancer properties. Previously, bromelain has been chromatographically separated into four fractions. Fraction 3 (F3) exhibits the highest proteolytic activity. The anticancer effects of F3 bromelain in CRC cells is unknown.
In vitro cytotoxicity was verified through a sulforhodamine B assay. Apoptosis in CRC cells induced by unfractionated or F3 bromelain was examined using Annexin V-FITC/PI staining and Western blot analysis. ROS status, autophagy and lysosome formation were determined by specific detection kit.
The cytotoxicity of F3 bromelain in CRC cells was found to be comparable to that of unfractionated bromelain. F3 bromelain induces caspase-dependent apoptosis in CRC cells. Treatment with unfractionated or F3 bromelain increased superoxide and oxidative stress levels and autophagy and lysosome formation. ATG5/12 and beclin-1 were upregulated, and the conversion of LC3B-I to LC3B-II was increased significantly by treatment with F3 bromelain. Treated CQ, autophagy inhibitor, with unfractionated or F3 bromelain enhances the cytotoxic effects. Finally, the combination of unfractionated and F3 bromelain with a routine chemotherapeutic agent (5-fluourouracil, irinotecan, or oxaliplatin) resulted in synergistically higher cytotoxic potency in CRC cells.
Unfractionated and F3 bromelain inhibits CRC cell proliferation in vitro, and the cytotoxic effects of unfractionated bromelain are equivalent to F3 bromelain. F3 bromelain may be a potential and potent drug for clinical use due to its anticancer efficacy and high synergistic cytotoxicity when combined with a routine chemotherapeutic agent for CRC.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>37262048</pmid><doi>10.1371/journal.pone.0285970</doi><tpages>e0285970</tpages><orcidid>https://orcid.org/0000-0003-3978-3244</orcidid><orcidid>https://orcid.org/0000-0001-8592-6336</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2023-06, Vol.18 (6), p.e0285970-e0285970 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2821629939 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Analysis Annexin V Anticancer properties Antimitotic agents Antineoplastic agents Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Apoptosis Autophagy Biology and Life Sciences Bromelains - pharmacology Cancer Cancer therapies Care and treatment Caspase Cell cycle Cell death Cell Line, Tumor Cell Proliferation Chemotherapy Chromatography Colonic Neoplasms - drug therapy Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - drug therapy Colorectal Neoplasms - pathology Cytotoxicity Diagnosis Dosage and administration Dyes Humans In vitro methods and tests Irinotecan Irinotecan - therapeutic use Medicine and Health Sciences Metastases Metastasis Oxaliplatin Oxidative stress Patient outcomes Physical Sciences Plant extracts Polymerase chain reaction Prevention Proteins Proteolysis Reagents Risk factors Sodium Sulforhodamine Superoxide Survival Thermal cycling Toxicity |
| title | Cytotoxic properties of unfractionated and fractionated bromelain alone or in combination with chemotherapeutic agents in colorectal cancer cells |
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