Graviola: A novel promising natural-derived drug that inhibits tumorigenicity and metastasis of pancreatic cancer cells in vitro and in vivo through altering cell metabolism
Pancreatic tumors are resistant to conventional chemotherapies. The present study was aimed at evaluating the potential of a novel plant-derived product as a therapeutic agent for pancreatic cancer (PC). The effects of an extract from the tropical tree Annona Muricata, commonly known as Graviola, wa...
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| Veröffentlicht in: | Cancer letters 2012-10, Vol.323 (1), p.29-40 |
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| creator | Torres, María P Rachagani, Satyanarayana Purohit, Vinee Pandey, Poomy Joshi, Suhasini Moore, Erik D Johansson, Sonny L Singh, Pankaj K Ganti, Apar K Batra, Surinder K |
| description | Pancreatic tumors are resistant to conventional chemotherapies. The present study was aimed at evaluating the potential of a novel plant-derived product as a therapeutic agent for pancreatic cancer (PC). The effects of an extract from the tropical tree Annona Muricata, commonly known as Graviola, was evaluated for cytotoxicity, cell metabolism, cancer-associated protein/gene expression, tumorigenicity, and metastatic properties of PC cells. Our experiments revealed that Graviola induced necrosis of PC cells by inhibiting cellular metabolism. The expression of molecules related to hypoxia and glycolysis in PC cells (i.e. HIF-1α, NF-κB, GLUT1, GLUT4, HKII, and LDHA) were downregulated in the presence of the extract. In vitro functional assays further confirmed the inhibition of tumorigenic properties of PC cells. Overall, the compounds that are naturally present in a Graviola extract inhibited multiple signaling pathways that regulate metabolism, cell cycle, survival, and metastatic properties in PC cells. Collectively, alterations in these parameters led to a decrease in tumorigenicity and metastasis of orthotopically implanted pancreatic tumors, indicating promising characteristics of the natural product against this lethal disease. |
| doi_str_mv | 10.1016/j.canlet.2012.03.031 |
| format | Article |
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The present study was aimed at evaluating the potential of a novel plant-derived product as a therapeutic agent for pancreatic cancer (PC). The effects of an extract from the tropical tree Annona Muricata, commonly known as Graviola, was evaluated for cytotoxicity, cell metabolism, cancer-associated protein/gene expression, tumorigenicity, and metastatic properties of PC cells. Our experiments revealed that Graviola induced necrosis of PC cells by inhibiting cellular metabolism. The expression of molecules related to hypoxia and glycolysis in PC cells (i.e. HIF-1α, NF-κB, GLUT1, GLUT4, HKII, and LDHA) were downregulated in the presence of the extract. In vitro functional assays further confirmed the inhibition of tumorigenic properties of PC cells. Overall, the compounds that are naturally present in a Graviola extract inhibited multiple signaling pathways that regulate metabolism, cell cycle, survival, and metastatic properties in PC cells. Collectively, alterations in these parameters led to a decrease in tumorigenicity and metastasis of orthotopically implanted pancreatic tumors, indicating promising characteristics of the natural product against this lethal disease.</description><identifier>ISSN: 0304-3835</identifier><identifier>EISSN: 1872-7980</identifier><identifier>DOI: 10.1016/j.canlet.2012.03.031</identifier><identifier>PMID: 22475682</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Animals ; Annona - chemistry ; Annona muricata ; Antineoplastic Agents - pharmacology ; Biological activity ; Blotting, Western ; Breast cancer ; Cancer metabolism ; Cancer therapies ; Cell culture ; Cell cycle ; Cell Line, Tumor ; Cell Movement - drug effects ; Cell survival ; Chemical compounds ; Chemotherapy ; Clinical trials ; Cytotoxicity ; Diabetes ; Disease ; Drug dosages ; drugs ; Female ; Gene expression ; Glycolysis ; Hematology, Oncology and Palliative Medicine ; Humans ; Hypoxia ; Medical prognosis ; Metabolism ; Metastases ; Metastasis ; Mice ; Mice, Nude ; Microscopy, Confocal ; Natural product ; Natural products ; Necrosis ; Neoplasms, Experimental - drug therapy ; Neoplasms, Experimental - metabolism ; Neoplasms, Experimental - pathology ; NF-κB protein ; Pancreatic cancer ; pancreatic neoplasms ; Pancreatic Neoplasms - metabolism ; Pheochromocytoma cells ; Phytotherapy - methods ; plant extracts ; Plant Extracts - pharmacology ; Plants ; Protein turnover ; Real-Time Polymerase Chain Reaction ; signal transduction ; Signal Transduction - drug effects ; Therapy ; trees ; Tumorigenicity ; Tumors ; Xenograft Model Antitumor Assays</subject><ispartof>Cancer letters, 2012-10, Vol.323 (1), p.29-40</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2012 Elsevier Ireland Ltd</rights><rights>Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.</rights><rights>2012. Elsevier Ireland Ltd</rights><rights>2012 Elsevier Ireland Ltd. All rights reserved. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c570t-443d0c4b999b22f22606b7f8f74c4f1cb9c028cb147f372f2a142f9bc289b8c43</citedby><cites>FETCH-LOGICAL-c570t-443d0c4b999b22f22606b7f8f74c4f1cb9c028cb147f372f2a142f9bc289b8c43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.canlet.2012.03.031$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22475682$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Torres, María P</creatorcontrib><creatorcontrib>Rachagani, Satyanarayana</creatorcontrib><creatorcontrib>Purohit, Vinee</creatorcontrib><creatorcontrib>Pandey, Poomy</creatorcontrib><creatorcontrib>Joshi, Suhasini</creatorcontrib><creatorcontrib>Moore, Erik D</creatorcontrib><creatorcontrib>Johansson, Sonny L</creatorcontrib><creatorcontrib>Singh, Pankaj K</creatorcontrib><creatorcontrib>Ganti, Apar K</creatorcontrib><creatorcontrib>Batra, Surinder K</creatorcontrib><title>Graviola: A novel promising natural-derived drug that inhibits tumorigenicity and metastasis of pancreatic cancer cells in vitro and in vivo through altering cell metabolism</title><title>Cancer letters</title><addtitle>Cancer Lett</addtitle><description>Pancreatic tumors are resistant to conventional chemotherapies. The present study was aimed at evaluating the potential of a novel plant-derived product as a therapeutic agent for pancreatic cancer (PC). The effects of an extract from the tropical tree Annona Muricata, commonly known as Graviola, was evaluated for cytotoxicity, cell metabolism, cancer-associated protein/gene expression, tumorigenicity, and metastatic properties of PC cells. Our experiments revealed that Graviola induced necrosis of PC cells by inhibiting cellular metabolism. The expression of molecules related to hypoxia and glycolysis in PC cells (i.e. HIF-1α, NF-κB, GLUT1, GLUT4, HKII, and LDHA) were downregulated in the presence of the extract. In vitro functional assays further confirmed the inhibition of tumorigenic properties of PC cells. Overall, the compounds that are naturally present in a Graviola extract inhibited multiple signaling pathways that regulate metabolism, cell cycle, survival, and metastatic properties in PC cells. Collectively, alterations in these parameters led to a decrease in tumorigenicity and metastasis of orthotopically implanted pancreatic tumors, indicating promising characteristics of the natural product against this lethal disease.</description><subject>Animals</subject><subject>Annona - chemistry</subject><subject>Annona muricata</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Biological activity</subject><subject>Blotting, Western</subject><subject>Breast cancer</subject><subject>Cancer metabolism</subject><subject>Cancer therapies</subject><subject>Cell culture</subject><subject>Cell cycle</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Cell survival</subject><subject>Chemical compounds</subject><subject>Chemotherapy</subject><subject>Clinical trials</subject><subject>Cytotoxicity</subject><subject>Diabetes</subject><subject>Disease</subject><subject>Drug dosages</subject><subject>drugs</subject><subject>Female</subject><subject>Gene expression</subject><subject>Glycolysis</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Medical prognosis</subject><subject>Metabolism</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Microscopy, Confocal</subject><subject>Natural product</subject><subject>Natural products</subject><subject>Necrosis</subject><subject>Neoplasms, Experimental - drug therapy</subject><subject>Neoplasms, Experimental - metabolism</subject><subject>Neoplasms, Experimental - pathology</subject><subject>NF-κB protein</subject><subject>Pancreatic cancer</subject><subject>pancreatic neoplasms</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Pheochromocytoma cells</subject><subject>Phytotherapy - methods</subject><subject>plant extracts</subject><subject>Plant Extracts - pharmacology</subject><subject>Plants</subject><subject>Protein turnover</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>signal transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Therapy</subject><subject>trees</subject><subject>Tumorigenicity</subject><subject>Tumors</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0304-3835</issn><issn>1872-7980</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUttu1DAQjRCILoU_QGCpz1nGl9x4QKoqKEiVeCh9thzHyc7ixIvtRNqP4h_x7pZSeEEaaWT5zJkzcybLXlNYU6Dlu-1aq8mauGZA2Rp4CvokW9G6YnnV1PA0WwEHkfOaF2fZixC2AFCIqnienTGWclmzVfbz2qsFnVXvySWZ3GIs2Xk3YsBpIJOKs1c274zHxXSk8_NA4kZFgtMGW4yBxHl0Hgczoca4J2rqyGiiCikwENeTnZq0NyqiJkmvNp5oY21IDGTB6N2x5PhYXOL2bh42RNmYWiYFB-yRsHUWw_gye9YrG8yr-3ye3X36-O3qc37z9frL1eVNrosKYi4E70CLtmmalrGesRLKturrvhJa9FS3jQZW65aKqudVAigqWN-0mtVNW2vBz7MPJ97d3I6m02aKaQ9y53FUfi-dQvn3z4QbObhFcl5RKiARXNwTePdjNiHKrZv9lDRLWkAJVSlomVDihNLeheBN_9CBgjyYLLfyZLI8mCyBp6Cp7M1jdQ9Fv11NgLcnQK-cVIPHIO9uE0ORLoBzCo8GNGmLCxovg0aT7OnQGx1l5_B_Gv4l0BbTESj73exN-DOtDKlG3h5O8XCJlAEwKgr-C3pl3Tk</recordid><startdate>20121001</startdate><enddate>20121001</enddate><creator>Torres, María P</creator><creator>Rachagani, Satyanarayana</creator><creator>Purohit, Vinee</creator><creator>Pandey, Poomy</creator><creator>Joshi, Suhasini</creator><creator>Moore, Erik D</creator><creator>Johansson, Sonny L</creator><creator>Singh, Pankaj K</creator><creator>Ganti, Apar K</creator><creator>Batra, Surinder K</creator><general>Elsevier B.V</general><general>Elsevier Ireland Ltd</general><general>Elsevier Limited</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>5PM</scope></search><sort><creationdate>20121001</creationdate><title>Graviola: A novel promising natural-derived drug that inhibits tumorigenicity and metastasis of pancreatic cancer cells in vitro and in vivo through altering cell metabolism</title><author>Torres, María P ; Rachagani, Satyanarayana ; Purohit, Vinee ; Pandey, Poomy ; Joshi, Suhasini ; Moore, Erik D ; Johansson, Sonny L ; Singh, Pankaj K ; Ganti, Apar K ; Batra, Surinder K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c570t-443d0c4b999b22f22606b7f8f74c4f1cb9c028cb147f372f2a142f9bc289b8c43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Annona - chemistry</topic><topic>Annona muricata</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Biological activity</topic><topic>Blotting, Western</topic><topic>Breast cancer</topic><topic>Cancer metabolism</topic><topic>Cancer therapies</topic><topic>Cell culture</topic><topic>Cell cycle</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - drug effects</topic><topic>Cell survival</topic><topic>Chemical compounds</topic><topic>Chemotherapy</topic><topic>Clinical trials</topic><topic>Cytotoxicity</topic><topic>Diabetes</topic><topic>Disease</topic><topic>Drug dosages</topic><topic>drugs</topic><topic>Female</topic><topic>Gene expression</topic><topic>Glycolysis</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Medical prognosis</topic><topic>Metabolism</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Microscopy, Confocal</topic><topic>Natural product</topic><topic>Natural products</topic><topic>Necrosis</topic><topic>Neoplasms, Experimental - drug therapy</topic><topic>Neoplasms, Experimental - metabolism</topic><topic>Neoplasms, Experimental - pathology</topic><topic>NF-κB protein</topic><topic>Pancreatic cancer</topic><topic>pancreatic neoplasms</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Pheochromocytoma cells</topic><topic>Phytotherapy - methods</topic><topic>plant extracts</topic><topic>Plant Extracts - pharmacology</topic><topic>Plants</topic><topic>Protein turnover</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>signal transduction</topic><topic>Signal Transduction - drug effects</topic><topic>Therapy</topic><topic>trees</topic><topic>Tumorigenicity</topic><topic>Tumors</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Torres, María P</creatorcontrib><creatorcontrib>Rachagani, Satyanarayana</creatorcontrib><creatorcontrib>Purohit, Vinee</creatorcontrib><creatorcontrib>Pandey, Poomy</creatorcontrib><creatorcontrib>Joshi, Suhasini</creatorcontrib><creatorcontrib>Moore, Erik D</creatorcontrib><creatorcontrib>Johansson, Sonny L</creatorcontrib><creatorcontrib>Singh, Pankaj K</creatorcontrib><creatorcontrib>Ganti, Apar K</creatorcontrib><creatorcontrib>Batra, Surinder K</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Torres, María P</au><au>Rachagani, Satyanarayana</au><au>Purohit, Vinee</au><au>Pandey, Poomy</au><au>Joshi, Suhasini</au><au>Moore, Erik D</au><au>Johansson, Sonny L</au><au>Singh, Pankaj K</au><au>Ganti, Apar K</au><au>Batra, Surinder K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Graviola: A novel promising natural-derived drug that inhibits tumorigenicity and metastasis of pancreatic cancer cells in vitro and in vivo through altering cell metabolism</atitle><jtitle>Cancer letters</jtitle><addtitle>Cancer Lett</addtitle><date>2012-10-01</date><risdate>2012</risdate><volume>323</volume><issue>1</issue><spage>29</spage><epage>40</epage><pages>29-40</pages><issn>0304-3835</issn><eissn>1872-7980</eissn><abstract>Pancreatic tumors are resistant to conventional chemotherapies. The present study was aimed at evaluating the potential of a novel plant-derived product as a therapeutic agent for pancreatic cancer (PC). The effects of an extract from the tropical tree Annona Muricata, commonly known as Graviola, was evaluated for cytotoxicity, cell metabolism, cancer-associated protein/gene expression, tumorigenicity, and metastatic properties of PC cells. Our experiments revealed that Graviola induced necrosis of PC cells by inhibiting cellular metabolism. The expression of molecules related to hypoxia and glycolysis in PC cells (i.e. HIF-1α, NF-κB, GLUT1, GLUT4, HKII, and LDHA) were downregulated in the presence of the extract. In vitro functional assays further confirmed the inhibition of tumorigenic properties of PC cells. Overall, the compounds that are naturally present in a Graviola extract inhibited multiple signaling pathways that regulate metabolism, cell cycle, survival, and metastatic properties in PC cells. Collectively, alterations in these parameters led to a decrease in tumorigenicity and metastasis of orthotopically implanted pancreatic tumors, indicating promising characteristics of the natural product against this lethal disease.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>22475682</pmid><doi>10.1016/j.canlet.2012.03.031</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Annona - chemistry Annona muricata Antineoplastic Agents - pharmacology Biological activity Blotting, Western Breast cancer Cancer metabolism Cancer therapies Cell culture Cell cycle Cell Line, Tumor Cell Movement - drug effects Cell survival Chemical compounds Chemotherapy Clinical trials Cytotoxicity Diabetes Disease Drug dosages drugs Female Gene expression Glycolysis Hematology, Oncology and Palliative Medicine Humans Hypoxia Medical prognosis Metabolism Metastases Metastasis Mice Mice, Nude Microscopy, Confocal Natural product Natural products Necrosis Neoplasms, Experimental - drug therapy Neoplasms, Experimental - metabolism Neoplasms, Experimental - pathology NF-κB protein Pancreatic cancer pancreatic neoplasms Pancreatic Neoplasms - metabolism Pheochromocytoma cells Phytotherapy - methods plant extracts Plant Extracts - pharmacology Plants Protein turnover Real-Time Polymerase Chain Reaction signal transduction Signal Transduction - drug effects Therapy trees Tumorigenicity Tumors Xenograft Model Antitumor Assays |
| title | Graviola: A novel promising natural-derived drug that inhibits tumorigenicity and metastasis of pancreatic cancer cells in vitro and in vivo through altering cell metabolism |
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