Combined ginger extract & Gelam honey modulate Ras/ERK and PI3K/AKT pathway genes in colon cancer HT29 cells
BACKGROUND: The interconnected Ras/ERK and PI3K/AKT pathways play a central role in colorectal tumorigenesis, and they are targets for elucidating mechanisms involved in attempts to induce colon cancer cell death. Both ginger (Zingiber officinale) and honey have been shown to exhibit anti-tumor and...
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| Veröffentlicht in: | Nutrition journal 2015-04, Vol.14 (1), p.31-15, Article 31 |
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| creator | Tahir, Analhuda Abdullah Sani, Nur Fathiah Abdul Murad, Noor Azian Makpol, Suzana Ngah, Wan Zurinah Wan Yusof, Yasmin Anum Mohd |
| description | BACKGROUND: The interconnected Ras/ERK and PI3K/AKT pathways play a central role in colorectal tumorigenesis, and they are targets for elucidating mechanisms involved in attempts to induce colon cancer cell death. Both ginger (Zingiber officinale) and honey have been shown to exhibit anti-tumor and anti-inflammation properties against many types of cancer, including colorectal cancer. However, there are currently no reports showing the combined effect of these two dietary compounds in cancer growth inhibition. The aim of this study was to evaluate the synergistic effect of crude ginger extract and Gelam honey in combination as potential cancer chemopreventive agents against the colorectal cancer cell line HT29. METHODS: The cells were divided into 4 groups: the first group represents HT29 cells without treatment, the second and third groups were cells treated singly with either ginger or Gelam honey, respectively, and the last group represents cells treated with ginger and Gelam honey combined. RESULTS: The results of MTS assay showed that the IC₅₀ of ginger and Gelam honey alone were 5.2 mg/ml and 80 mg/ml, respectively, whereas the IC₅₀ of the combination treatment was 3 mg/ml of ginger plus 27 mg/ml of Gelam honey with a combination index of < 1, suggesting synergism. Cell death in response to the combined ginger and Gelam honey treatment was associated with the stimulation of early apoptosis (upregulation of caspase 9 and IκB genes) accompanied by downregulation of the KRAS, ERK, AKT, Bcl-xL, NFkB (p65) genes in a synergistic manner. CONCLUSIONS: In conclusion, the combination of ginger and Gelam honey may be an effective chemopreventive and therapeutic strategy for inducing the death of colon cancer cells. |
| doi_str_mv | 10.1186/s12937-015-0015-2 |
| format | Article |
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Both ginger (Zingiber officinale) and honey have been shown to exhibit anti-tumor and anti-inflammation properties against many types of cancer, including colorectal cancer. However, there are currently no reports showing the combined effect of these two dietary compounds in cancer growth inhibition. The aim of this study was to evaluate the synergistic effect of crude ginger extract and Gelam honey in combination as potential cancer chemopreventive agents against the colorectal cancer cell line HT29. METHODS: The cells were divided into 4 groups: the first group represents HT29 cells without treatment, the second and third groups were cells treated singly with either ginger or Gelam honey, respectively, and the last group represents cells treated with ginger and Gelam honey combined. RESULTS: The results of MTS assay showed that the IC₅₀ of ginger and Gelam honey alone were 5.2 mg/ml and 80 mg/ml, respectively, whereas the IC₅₀ of the combination treatment was 3 mg/ml of ginger plus 27 mg/ml of Gelam honey with a combination index of < 1, suggesting synergism. Cell death in response to the combined ginger and Gelam honey treatment was associated with the stimulation of early apoptosis (upregulation of caspase 9 and IκB genes) accompanied by downregulation of the KRAS, ERK, AKT, Bcl-xL, NFkB (p65) genes in a synergistic manner. CONCLUSIONS: In conclusion, the combination of ginger and Gelam honey may be an effective chemopreventive and therapeutic strategy for inducing the death of colon cancer cells.</description><identifier>ISSN: 1475-2891</identifier><identifier>EISSN: 1475-2891</identifier><identifier>DOI: 10.1186/s12937-015-0015-2</identifier><identifier>PMID: 25889965</identifier><language>eng</language><publisher>England: Springer-Verlag</publisher><subject>anti-inflammatory activity ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - pharmacology ; apoptosis ; Apoptosis - drug effects ; Apoptosis - genetics ; bcl-X Protein - genetics ; Cancer ; carcinogenesis ; Care and treatment ; Caspase 9 - genetics ; caspases ; Cell death ; chemoprevention ; Colonic Neoplasms - drug therapy ; Colonic Neoplasms - genetics ; Colonic Neoplasms - pathology ; colorectal neoplasms ; death ; Down-Regulation - drug effects ; Drug Therapy, Combination - methods ; Gene Expression - drug effects ; gene expression regulation ; genes ; Genetic aspects ; ginger ; growth retardation ; Health aspects ; Honey ; HT29 Cells ; Humans ; Inflammation - drug therapy ; Inflammation - genetics ; inhibitory concentration 50 ; MAP Kinase Signaling System - drug effects ; MAP Kinase Signaling System - genetics ; mitogen-activated protein kinase ; neoplasm cells ; NF-kappaB-Inducing Kinase ; Oncogene Protein v-akt - genetics ; Oncology, Experimental ; Phytotherapy - methods ; Plant Extracts - chemistry ; Plant Extracts - pharmacology ; Plant Preparations - chemistry ; Plant Preparations - pharmacology ; Protein Serine-Threonine Kinases - genetics ; Protein Tyrosine Phosphatases - genetics ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins p21(ras) ; ras Proteins - genetics ; synergism ; Treatment Outcome ; Up-Regulation - drug effects ; Zingiber officinale ; Zingiber officinale - chemistry</subject><ispartof>Nutrition journal, 2015-04, Vol.14 (1), p.31-15, Article 31</ispartof><rights>COPYRIGHT 2015 BioMed Central Ltd.</rights><rights>Abdulah Tahir et al.; licensee BioMed Central. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c557t-9269e3b336ab0c483e9ecefa97449e073ac993ad22428744eea9f2f0a30217ec3</citedby><cites>FETCH-LOGICAL-c557t-9269e3b336ab0c483e9ecefa97449e073ac993ad22428744eea9f2f0a30217ec3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4390091/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4390091/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25889965$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tahir, Analhuda Abdullah</creatorcontrib><creatorcontrib>Sani, Nur Fathiah Abdul</creatorcontrib><creatorcontrib>Murad, Noor Azian</creatorcontrib><creatorcontrib>Makpol, Suzana</creatorcontrib><creatorcontrib>Ngah, Wan Zurinah Wan</creatorcontrib><creatorcontrib>Yusof, Yasmin Anum Mohd</creatorcontrib><title>Combined ginger extract & Gelam honey modulate Ras/ERK and PI3K/AKT pathway genes in colon cancer HT29 cells</title><title>Nutrition journal</title><addtitle>Nutr J</addtitle><description>BACKGROUND: The interconnected Ras/ERK and PI3K/AKT pathways play a central role in colorectal tumorigenesis, and they are targets for elucidating mechanisms involved in attempts to induce colon cancer cell death. Both ginger (Zingiber officinale) and honey have been shown to exhibit anti-tumor and anti-inflammation properties against many types of cancer, including colorectal cancer. However, there are currently no reports showing the combined effect of these two dietary compounds in cancer growth inhibition. The aim of this study was to evaluate the synergistic effect of crude ginger extract and Gelam honey in combination as potential cancer chemopreventive agents against the colorectal cancer cell line HT29. METHODS: The cells were divided into 4 groups: the first group represents HT29 cells without treatment, the second and third groups were cells treated singly with either ginger or Gelam honey, respectively, and the last group represents cells treated with ginger and Gelam honey combined. RESULTS: The results of MTS assay showed that the IC₅₀ of ginger and Gelam honey alone were 5.2 mg/ml and 80 mg/ml, respectively, whereas the IC₅₀ of the combination treatment was 3 mg/ml of ginger plus 27 mg/ml of Gelam honey with a combination index of < 1, suggesting synergism. Cell death in response to the combined ginger and Gelam honey treatment was associated with the stimulation of early apoptosis (upregulation of caspase 9 and IκB genes) accompanied by downregulation of the KRAS, ERK, AKT, Bcl-xL, NFkB (p65) genes in a synergistic manner. CONCLUSIONS: In conclusion, the combination of ginger and Gelam honey may be an effective chemopreventive and therapeutic strategy for inducing the death of colon cancer cells.</description><subject>anti-inflammatory activity</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - genetics</subject><subject>bcl-X Protein - genetics</subject><subject>Cancer</subject><subject>carcinogenesis</subject><subject>Care and treatment</subject><subject>Caspase 9 - genetics</subject><subject>caspases</subject><subject>Cell death</subject><subject>chemoprevention</subject><subject>Colonic Neoplasms - drug therapy</subject><subject>Colonic Neoplasms - genetics</subject><subject>Colonic Neoplasms - pathology</subject><subject>colorectal neoplasms</subject><subject>death</subject><subject>Down-Regulation - drug effects</subject><subject>Drug Therapy, Combination - methods</subject><subject>Gene Expression - drug effects</subject><subject>gene expression regulation</subject><subject>genes</subject><subject>Genetic aspects</subject><subject>ginger</subject><subject>growth retardation</subject><subject>Health aspects</subject><subject>Honey</subject><subject>HT29 Cells</subject><subject>Humans</subject><subject>Inflammation - drug therapy</subject><subject>Inflammation - genetics</subject><subject>inhibitory concentration 50</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>MAP Kinase Signaling System - genetics</subject><subject>mitogen-activated protein kinase</subject><subject>neoplasm cells</subject><subject>NF-kappaB-Inducing Kinase</subject><subject>Oncogene Protein v-akt - genetics</subject><subject>Oncology, Experimental</subject><subject>Phytotherapy - methods</subject><subject>Plant Extracts - chemistry</subject><subject>Plant Extracts - pharmacology</subject><subject>Plant Preparations - chemistry</subject><subject>Plant Preparations - pharmacology</subject><subject>Protein Serine-Threonine Kinases - genetics</subject><subject>Protein Tyrosine Phosphatases - genetics</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Proto-Oncogene Proteins p21(ras)</subject><subject>ras Proteins - genetics</subject><subject>synergism</subject><subject>Treatment Outcome</subject><subject>Up-Regulation - drug effects</subject><subject>Zingiber officinale</subject><subject>Zingiber officinale - chemistry</subject><issn>1475-2891</issn><issn>1475-2891</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkm1rFDEQxxdRbK1-AN9oQBB9cb087EPyRjiO2h5XUK7X12EuO7sX2U3Oza56394sW0sPJDAZJr__wEz-SfKW0UvGZD4PjCtRzCjLZnQM_FlyztIiJlKx50_ys-RVCD8o5VKq4mVyxrOYqDw7T5qlb3fWYUlq62rsCP7pOzA9-UiusYGW7L3DI2l9OTTQI9lAmF9t1gRcSb6vxHq-WG_JAfr9bziSGh0GYh0xvvExgjOx482WK2KwacLr5EUFTcA3D_dFcv_1aru8md1-u14tF7czk2VFP1M8Vyh2QuSwoyaVAhUarEAVaaqQFgKMUgJKzlMuYw0RVMUrCoJyVqARF8mXqe9h2LVYGnRxpkYfOttCd9QerD59cXava_9Lp0JRqlhs8OmhQed_Dhh63dowjgAO_RA0k1RQmSuVRfTDhNbQoLau8uP-RlwvspSlMssVj9Tlf6h4SmytiSuubKyfCD6fCCLTx6-pYQhBr-42pyybWNP5EDqsHidlVI9G0ZNRdPSIHo2iR827pyt6VPxzRgTeT0AFXkPd2aDv7zhlOaVUFnFP4i8Ozb84</recordid><startdate>20150401</startdate><enddate>20150401</enddate><creator>Tahir, Analhuda Abdullah</creator><creator>Sani, Nur Fathiah Abdul</creator><creator>Murad, Noor Azian</creator><creator>Makpol, Suzana</creator><creator>Ngah, Wan Zurinah Wan</creator><creator>Yusof, Yasmin Anum Mohd</creator><general>Springer-Verlag</general><general>BioMed Central Ltd</general><general>BioMed Central</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>ISR</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20150401</creationdate><title>Combined ginger extract & Gelam honey modulate Ras/ERK and PI3K/AKT pathway genes in colon cancer HT29 cells</title><author>Tahir, Analhuda Abdullah ; Sani, Nur Fathiah Abdul ; Murad, Noor Azian ; Makpol, Suzana ; Ngah, Wan Zurinah Wan ; Yusof, Yasmin Anum Mohd</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c557t-9269e3b336ab0c483e9ecefa97449e073ac993ad22428744eea9f2f0a30217ec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>anti-inflammatory activity</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - genetics</topic><topic>bcl-X Protein - genetics</topic><topic>Cancer</topic><topic>carcinogenesis</topic><topic>Care and treatment</topic><topic>Caspase 9 - genetics</topic><topic>caspases</topic><topic>Cell death</topic><topic>chemoprevention</topic><topic>Colonic Neoplasms - drug therapy</topic><topic>Colonic Neoplasms - genetics</topic><topic>Colonic Neoplasms - pathology</topic><topic>colorectal neoplasms</topic><topic>death</topic><topic>Down-Regulation - drug effects</topic><topic>Drug Therapy, Combination - methods</topic><topic>Gene Expression - drug effects</topic><topic>gene expression regulation</topic><topic>genes</topic><topic>Genetic aspects</topic><topic>ginger</topic><topic>growth retardation</topic><topic>Health aspects</topic><topic>Honey</topic><topic>HT29 Cells</topic><topic>Humans</topic><topic>Inflammation - drug therapy</topic><topic>Inflammation - genetics</topic><topic>inhibitory concentration 50</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>MAP Kinase Signaling System - genetics</topic><topic>mitogen-activated protein kinase</topic><topic>neoplasm cells</topic><topic>NF-kappaB-Inducing Kinase</topic><topic>Oncogene Protein v-akt - genetics</topic><topic>Oncology, Experimental</topic><topic>Phytotherapy - methods</topic><topic>Plant Extracts - chemistry</topic><topic>Plant Extracts - pharmacology</topic><topic>Plant Preparations - chemistry</topic><topic>Plant Preparations - pharmacology</topic><topic>Protein Serine-Threonine Kinases - genetics</topic><topic>Protein Tyrosine Phosphatases - genetics</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Proto-Oncogene Proteins p21(ras)</topic><topic>ras Proteins - genetics</topic><topic>synergism</topic><topic>Treatment Outcome</topic><topic>Up-Regulation - drug effects</topic><topic>Zingiber officinale</topic><topic>Zingiber officinale - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tahir, Analhuda Abdullah</creatorcontrib><creatorcontrib>Sani, Nur Fathiah Abdul</creatorcontrib><creatorcontrib>Murad, Noor Azian</creatorcontrib><creatorcontrib>Makpol, Suzana</creatorcontrib><creatorcontrib>Ngah, Wan Zurinah Wan</creatorcontrib><creatorcontrib>Yusof, Yasmin Anum Mohd</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>Gale In Context: Science</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nutrition journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tahir, Analhuda Abdullah</au><au>Sani, Nur Fathiah Abdul</au><au>Murad, Noor Azian</au><au>Makpol, Suzana</au><au>Ngah, Wan Zurinah Wan</au><au>Yusof, Yasmin Anum Mohd</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Combined ginger extract & Gelam honey modulate Ras/ERK and PI3K/AKT pathway genes in colon cancer HT29 cells</atitle><jtitle>Nutrition journal</jtitle><addtitle>Nutr J</addtitle><date>2015-04-01</date><risdate>2015</risdate><volume>14</volume><issue>1</issue><spage>31</spage><epage>15</epage><pages>31-15</pages><artnum>31</artnum><issn>1475-2891</issn><eissn>1475-2891</eissn><abstract>BACKGROUND: The interconnected Ras/ERK and PI3K/AKT pathways play a central role in colorectal tumorigenesis, and they are targets for elucidating mechanisms involved in attempts to induce colon cancer cell death. Both ginger (Zingiber officinale) and honey have been shown to exhibit anti-tumor and anti-inflammation properties against many types of cancer, including colorectal cancer. However, there are currently no reports showing the combined effect of these two dietary compounds in cancer growth inhibition. The aim of this study was to evaluate the synergistic effect of crude ginger extract and Gelam honey in combination as potential cancer chemopreventive agents against the colorectal cancer cell line HT29. METHODS: The cells were divided into 4 groups: the first group represents HT29 cells without treatment, the second and third groups were cells treated singly with either ginger or Gelam honey, respectively, and the last group represents cells treated with ginger and Gelam honey combined. RESULTS: The results of MTS assay showed that the IC₅₀ of ginger and Gelam honey alone were 5.2 mg/ml and 80 mg/ml, respectively, whereas the IC₅₀ of the combination treatment was 3 mg/ml of ginger plus 27 mg/ml of Gelam honey with a combination index of < 1, suggesting synergism. Cell death in response to the combined ginger and Gelam honey treatment was associated with the stimulation of early apoptosis (upregulation of caspase 9 and IκB genes) accompanied by downregulation of the KRAS, ERK, AKT, Bcl-xL, NFkB (p65) genes in a synergistic manner. CONCLUSIONS: In conclusion, the combination of ginger and Gelam honey may be an effective chemopreventive and therapeutic strategy for inducing the death of colon cancer cells.</abstract><cop>England</cop><pub>Springer-Verlag</pub><pmid>25889965</pmid><doi>10.1186/s12937-015-0015-2</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | anti-inflammatory activity Antineoplastic Agents - administration & dosage Antineoplastic Agents - pharmacology apoptosis Apoptosis - drug effects Apoptosis - genetics bcl-X Protein - genetics Cancer carcinogenesis Care and treatment Caspase 9 - genetics caspases Cell death chemoprevention Colonic Neoplasms - drug therapy Colonic Neoplasms - genetics Colonic Neoplasms - pathology colorectal neoplasms death Down-Regulation - drug effects Drug Therapy, Combination - methods Gene Expression - drug effects gene expression regulation genes Genetic aspects ginger growth retardation Health aspects Honey HT29 Cells Humans Inflammation - drug therapy Inflammation - genetics inhibitory concentration 50 MAP Kinase Signaling System - drug effects MAP Kinase Signaling System - genetics mitogen-activated protein kinase neoplasm cells NF-kappaB-Inducing Kinase Oncogene Protein v-akt - genetics Oncology, Experimental Phytotherapy - methods Plant Extracts - chemistry Plant Extracts - pharmacology Plant Preparations - chemistry Plant Preparations - pharmacology Protein Serine-Threonine Kinases - genetics Protein Tyrosine Phosphatases - genetics Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins p21(ras) ras Proteins - genetics synergism Treatment Outcome Up-Regulation - drug effects Zingiber officinale Zingiber officinale - chemistry |
| title | Combined ginger extract & Gelam honey modulate Ras/ERK and PI3K/AKT pathway genes in colon cancer HT29 cells |
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