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Dietary Crocin is Protective in Pancreatic Cancer while Reducing Radiation-Induced Hepatic Oxidative Damage
Pancreatic cancer is one of the fatal causes of global cancer-related deaths. Although surgery and chemotherapy are standard treatment options, post-treatment outcomes often end in a poor prognosis. In the present study, we investigated anti-pancreatic cancer and amelioration of radiation-induced ox...
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Published in: | Nutrients 2020-06, Vol.12 (6), p.1901 |
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creator | Bakshi, Hamid A Zoubi, Mazhar S Al Hakkim, Faruck L Aljabali, Alaa A A Rabi, Firas A Hafiz, Amin A Al-Batanyeh, Khalid M Al-Trad, Bahaa Ansari, Prawej Nasef, Mohamed M Charbe, Nitin B Satija, Saurabh Mehta, Meenu Mishra, Vijay Gupta, Gaurav Abobaker, Salem Negi, Poonam Azzouz, Ibrahim M Dardouri, Ashref Ali K Dureja, Harish Prasher, Parteek Chellappan, Dinesh K Dua, Kamal Webba da Silva, Mateus El Tanani, Mohamed McCarron, Paul A Tambuwala, Murtaza M |
description | Pancreatic cancer is one of the fatal causes of global cancer-related deaths. Although surgery and chemotherapy are standard treatment options, post-treatment outcomes often end in a poor prognosis. In the present study, we investigated anti-pancreatic cancer and amelioration of radiation-induced oxidative damage by crocin. Crocin is a carotenoid isolated from the dietary herb saffron, a prospect for novel leads as an anti-cancer agent. Crocin significantly reduced cell viability of BXPC3 and Capan-2 by triggering caspase signaling via the downregulation of Bcl-2. It modulated the expression of cell cycle signaling proteins P53, P21, P27, CDK2, c-MYC, Cyt-c and P38. Concomitantly, crocin treatment-induced apoptosis by inducing the release of cytochrome c from mitochondria to cytosol. Microarray analysis of the expression signature of genes induced by crocin showed a substantial number of genes involved in cell signaling pathways and checkpoints (723) are significantly affected by crocin. In mice bearing pancreatic tumors, crocin significantly reduced tumor burden without a change in body weight. Additionally, it showed significant protection against radiation-induced hepatic oxidative damage, reduced the levels of hepatic toxicity and preserved liver morphology. These findings indicate that crocin has a potential role in the treatment, prevention and management of pancreatic cancer. |
doi_str_mv | 10.3390/nu12061901 |
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Although surgery and chemotherapy are standard treatment options, post-treatment outcomes often end in a poor prognosis. In the present study, we investigated anti-pancreatic cancer and amelioration of radiation-induced oxidative damage by crocin. Crocin is a carotenoid isolated from the dietary herb saffron, a prospect for novel leads as an anti-cancer agent. Crocin significantly reduced cell viability of BXPC3 and Capan-2 by triggering caspase signaling via the downregulation of Bcl-2. It modulated the expression of cell cycle signaling proteins P53, P21, P27, CDK2, c-MYC, Cyt-c and P38. Concomitantly, crocin treatment-induced apoptosis by inducing the release of cytochrome c from mitochondria to cytosol. Microarray analysis of the expression signature of genes induced by crocin showed a substantial number of genes involved in cell signaling pathways and checkpoints (723) are significantly affected by crocin. In mice bearing pancreatic tumors, crocin significantly reduced tumor burden without a change in body weight. Additionally, it showed significant protection against radiation-induced hepatic oxidative damage, reduced the levels of hepatic toxicity and preserved liver morphology. These findings indicate that crocin has a potential role in the treatment, prevention and management of pancreatic cancer.</description><identifier>ISSN: 2072-6643</identifier><identifier>EISSN: 2072-6643</identifier><identifier>DOI: 10.3390/nu12061901</identifier><identifier>PMID: 32604971</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Animals ; Antineoplastic Agents, Phytogenic ; Apoptosis ; Apoptosis - drug effects ; Bcl-2 protein ; Body weight ; c-Myc protein ; Cancer therapies ; Carotenoids - therapeutic use ; Caspase ; Cell cycle ; Cell Cycle Proteins - metabolism ; Cell Line, Tumor ; Cell Survival - drug effects ; Cell viability ; Chemotherapy ; Crocus - chemistry ; Cyclin-dependent kinase 2 ; Cytochrome ; Cytochrome c ; Cytochromes c - metabolism ; Cytosol ; Deoxyribonucleic acid ; DNA ; Female ; Gene expression ; Genes ; Humans ; Lipid Peroxidation - drug effects ; Liver ; Liver Diseases - etiology ; Liver Diseases - prevention & control ; Medical prognosis ; Mice ; Mice, Nude ; Mitochondria ; Myc protein ; p53 Protein ; Pancreatic cancer ; Pancreatic Neoplasms - drug therapy ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - radiotherapy ; Penicillin ; Radiation ; Radiation damage ; Radiation effects ; Radiation Injuries - prevention & control ; Radiation therapy ; Signal Transduction - drug effects ; Signal Transduction - genetics ; Toxicity ; Transcriptome ; Tumors ; Xenograft Model Antitumor Assays</subject><ispartof>Nutrients, 2020-06, Vol.12 (6), p.1901</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). 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Although surgery and chemotherapy are standard treatment options, post-treatment outcomes often end in a poor prognosis. In the present study, we investigated anti-pancreatic cancer and amelioration of radiation-induced oxidative damage by crocin. Crocin is a carotenoid isolated from the dietary herb saffron, a prospect for novel leads as an anti-cancer agent. Crocin significantly reduced cell viability of BXPC3 and Capan-2 by triggering caspase signaling via the downregulation of Bcl-2. It modulated the expression of cell cycle signaling proteins P53, P21, P27, CDK2, c-MYC, Cyt-c and P38. Concomitantly, crocin treatment-induced apoptosis by inducing the release of cytochrome c from mitochondria to cytosol. Microarray analysis of the expression signature of genes induced by crocin showed a substantial number of genes involved in cell signaling pathways and checkpoints (723) are significantly affected by crocin. In mice bearing pancreatic tumors, crocin significantly reduced tumor burden without a change in body weight. Additionally, it showed significant protection against radiation-induced hepatic oxidative damage, reduced the levels of hepatic toxicity and preserved liver morphology. These findings indicate that crocin has a potential role in the treatment, prevention and management of pancreatic cancer.</description><subject>Animals</subject><subject>Antineoplastic Agents, Phytogenic</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Bcl-2 protein</subject><subject>Body weight</subject><subject>c-Myc protein</subject><subject>Cancer therapies</subject><subject>Carotenoids - therapeutic use</subject><subject>Caspase</subject><subject>Cell cycle</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Cell viability</subject><subject>Chemotherapy</subject><subject>Crocus - chemistry</subject><subject>Cyclin-dependent kinase 2</subject><subject>Cytochrome</subject><subject>Cytochrome c</subject><subject>Cytochromes c - metabolism</subject><subject>Cytosol</subject><subject>Deoxyribonucleic 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Crocin is Protective in Pancreatic Cancer while Reducing Radiation-Induced Hepatic Oxidative Damage</title><author>Bakshi, Hamid A ; Zoubi, Mazhar S Al ; Hakkim, Faruck L ; Aljabali, Alaa A A ; Rabi, Firas A ; Hafiz, Amin A ; Al-Batanyeh, Khalid M ; Al-Trad, Bahaa ; Ansari, Prawej ; Nasef, Mohamed M ; Charbe, Nitin B ; Satija, Saurabh ; Mehta, Meenu ; Mishra, Vijay ; Gupta, Gaurav ; Abobaker, Salem ; Negi, Poonam ; Azzouz, Ibrahim M ; Dardouri, Ashref Ali K ; Dureja, Harish ; Prasher, Parteek ; Chellappan, Dinesh K ; Dua, Kamal ; Webba da Silva, Mateus ; El Tanani, Mohamed ; McCarron, Paul A ; Tambuwala, Murtaza M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c406t-cf5390ab0beb0e39035267b30c1ce679bce681aad9847f3056d7aed8e5f7f31a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Antineoplastic Agents, 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Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bakshi, Hamid A</au><au>Zoubi, Mazhar S Al</au><au>Hakkim, Faruck L</au><au>Aljabali, Alaa A A</au><au>Rabi, Firas A</au><au>Hafiz, Amin A</au><au>Al-Batanyeh, Khalid M</au><au>Al-Trad, Bahaa</au><au>Ansari, Prawej</au><au>Nasef, Mohamed M</au><au>Charbe, Nitin B</au><au>Satija, Saurabh</au><au>Mehta, Meenu</au><au>Mishra, Vijay</au><au>Gupta, Gaurav</au><au>Abobaker, Salem</au><au>Negi, Poonam</au><au>Azzouz, Ibrahim M</au><au>Dardouri, Ashref Ali K</au><au>Dureja, Harish</au><au>Prasher, Parteek</au><au>Chellappan, Dinesh K</au><au>Dua, Kamal</au><au>Webba da Silva, Mateus</au><au>El Tanani, Mohamed</au><au>McCarron, Paul A</au><au>Tambuwala, Murtaza M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dietary Crocin is Protective in Pancreatic Cancer while Reducing Radiation-Induced Hepatic Oxidative Damage</atitle><jtitle>Nutrients</jtitle><addtitle>Nutrients</addtitle><date>2020-06-26</date><risdate>2020</risdate><volume>12</volume><issue>6</issue><spage>1901</spage><pages>1901-</pages><issn>2072-6643</issn><eissn>2072-6643</eissn><abstract>Pancreatic cancer is one of the fatal causes of global cancer-related deaths. Although surgery and chemotherapy are standard treatment options, post-treatment outcomes often end in a poor prognosis. In the present study, we investigated anti-pancreatic cancer and amelioration of radiation-induced oxidative damage by crocin. Crocin is a carotenoid isolated from the dietary herb saffron, a prospect for novel leads as an anti-cancer agent. Crocin significantly reduced cell viability of BXPC3 and Capan-2 by triggering caspase signaling via the downregulation of Bcl-2. It modulated the expression of cell cycle signaling proteins P53, P21, P27, CDK2, c-MYC, Cyt-c and P38. Concomitantly, crocin treatment-induced apoptosis by inducing the release of cytochrome c from mitochondria to cytosol. Microarray analysis of the expression signature of genes induced by crocin showed a substantial number of genes involved in cell signaling pathways and checkpoints (723) are significantly affected by crocin. In mice bearing pancreatic tumors, crocin significantly reduced tumor burden without a change in body weight. Additionally, it showed significant protection against radiation-induced hepatic oxidative damage, reduced the levels of hepatic toxicity and preserved liver morphology. These findings indicate that crocin has a potential role in the treatment, prevention and management of pancreatic cancer.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>32604971</pmid><doi>10.3390/nu12061901</doi><orcidid>https://orcid.org/0000-0002-9412-9424</orcidid><orcidid>https://orcid.org/0000-0003-0248-4777</orcidid><orcidid>https://orcid.org/0000-0002-0825-6276</orcidid><orcidid>https://orcid.org/0000-0002-3575-2443</orcidid><orcidid>https://orcid.org/0000-0001-8499-9891</orcidid><orcidid>https://orcid.org/0000-0001-7941-0229</orcidid><orcidid>https://orcid.org/0000-0001-5567-6663</orcidid><orcidid>https://orcid.org/0000-0002-9519-6338</orcidid><orcidid>https://orcid.org/0000-0002-1966-040X</orcidid><orcidid>https://orcid.org/0000-0002-2292-9887</orcidid><orcidid>https://orcid.org/0000-0002-2062-6241</orcidid><orcidid>https://orcid.org/0000-0001-9474-2766</orcidid><orcidid>https://orcid.org/0000-0001-8336-1984</orcidid><orcidid>https://orcid.org/0000-0002-7507-1159</orcidid><orcidid>https://orcid.org/0000-0001-6542-2464</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 2072-6643 |
ispartof | Nutrients, 2020-06, Vol.12 (6), p.1901 |
issn | 2072-6643 2072-6643 |
language | eng |
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source | Publicly Available Content (ProQuest); PubMed Central |
subjects | Animals Antineoplastic Agents, Phytogenic Apoptosis Apoptosis - drug effects Bcl-2 protein Body weight c-Myc protein Cancer therapies Carotenoids - therapeutic use Caspase Cell cycle Cell Cycle Proteins - metabolism Cell Line, Tumor Cell Survival - drug effects Cell viability Chemotherapy Crocus - chemistry Cyclin-dependent kinase 2 Cytochrome Cytochrome c Cytochromes c - metabolism Cytosol Deoxyribonucleic acid DNA Female Gene expression Genes Humans Lipid Peroxidation - drug effects Liver Liver Diseases - etiology Liver Diseases - prevention & control Medical prognosis Mice Mice, Nude Mitochondria Myc protein p53 Protein Pancreatic cancer Pancreatic Neoplasms - drug therapy Pancreatic Neoplasms - genetics Pancreatic Neoplasms - radiotherapy Penicillin Radiation Radiation damage Radiation effects Radiation Injuries - prevention & control Radiation therapy Signal Transduction - drug effects Signal Transduction - genetics Toxicity Transcriptome Tumors Xenograft Model Antitumor Assays |
title | Dietary Crocin is Protective in Pancreatic Cancer while Reducing Radiation-Induced Hepatic Oxidative Damage |
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