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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
Main Authors: 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
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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. 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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, Phytogenic</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Bcl-2 protein</topic><topic>Body weight</topic><topic>c-Myc protein</topic><topic>Cancer therapies</topic><topic>Carotenoids - therapeutic use</topic><topic>Caspase</topic><topic>Cell cycle</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>Cell viability</topic><topic>Chemotherapy</topic><topic>Crocus - chemistry</topic><topic>Cyclin-dependent kinase 2</topic><topic>Cytochrome</topic><topic>Cytochrome c</topic><topic>Cytochromes c - metabolism</topic><topic>Cytosol</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Female</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Humans</topic><topic>Lipid Peroxidation - drug effects</topic><topic>Liver</topic><topic>Liver Diseases - etiology</topic><topic>Liver Diseases - prevention &amp; control</topic><topic>Medical prognosis</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Mitochondria</topic><topic>Myc protein</topic><topic>p53 Protein</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - drug therapy</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>Pancreatic Neoplasms - radiotherapy</topic><topic>Penicillin</topic><topic>Radiation</topic><topic>Radiation damage</topic><topic>Radiation effects</topic><topic>Radiation Injuries - prevention &amp; control</topic><topic>Radiation therapy</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - genetics</topic><topic>Toxicity</topic><topic>Transcriptome</topic><topic>Tumors</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bakshi, Hamid A</creatorcontrib><creatorcontrib>Zoubi, Mazhar S Al</creatorcontrib><creatorcontrib>Hakkim, Faruck L</creatorcontrib><creatorcontrib>Aljabali, Alaa A A</creatorcontrib><creatorcontrib>Rabi, Firas A</creatorcontrib><creatorcontrib>Hafiz, Amin A</creatorcontrib><creatorcontrib>Al-Batanyeh, Khalid M</creatorcontrib><creatorcontrib>Al-Trad, Bahaa</creatorcontrib><creatorcontrib>Ansari, Prawej</creatorcontrib><creatorcontrib>Nasef, Mohamed M</creatorcontrib><creatorcontrib>Charbe, Nitin B</creatorcontrib><creatorcontrib>Satija, Saurabh</creatorcontrib><creatorcontrib>Mehta, Meenu</creatorcontrib><creatorcontrib>Mishra, Vijay</creatorcontrib><creatorcontrib>Gupta, Gaurav</creatorcontrib><creatorcontrib>Abobaker, Salem</creatorcontrib><creatorcontrib>Negi, Poonam</creatorcontrib><creatorcontrib>Azzouz, Ibrahim M</creatorcontrib><creatorcontrib>Dardouri, Ashref Ali K</creatorcontrib><creatorcontrib>Dureja, Harish</creatorcontrib><creatorcontrib>Prasher, Parteek</creatorcontrib><creatorcontrib>Chellappan, Dinesh K</creatorcontrib><creatorcontrib>Dua, Kamal</creatorcontrib><creatorcontrib>Webba da Silva, Mateus</creatorcontrib><creatorcontrib>El Tanani, Mohamed</creatorcontrib><creatorcontrib>McCarron, Paul A</creatorcontrib><creatorcontrib>Tambuwala, Murtaza M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Physical Education Index</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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 Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</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 Health &amp; Medical Complete (Alumni)</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Publicly Available Content (ProQuest)</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>PubMed Central (Full Participant titles)</collection><jtitle>Nutrients</jtitle></facets><delivery><delcategory>Remote Search 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>
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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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