Complementary effects of Orthosiphon stamineus standardized ethanolic extract and rosmarinic acid in combination with gemcitabine on pancreatic cancer
Pancreatic cancer is one of the most notorious cancers and is known for its highly invasive characteristics, drug resistance, and metastatic progression. Unfortunately, many patients with advanced pancreatic cancer become insensitive towards gemcitabine treatment. Orthosiphon stamineus (O.s) is used...
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| Veröffentlicht in: | Biomedical Journal 2021-12, Vol.44 (6), p.694-708 |
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| description | Pancreatic cancer is one of the most notorious cancers and is known for its highly invasive characteristics, drug resistance, and metastatic progression. Unfortunately, many patients with advanced pancreatic cancer become insensitive towards gemcitabine treatment. Orthosiphon stamineus (O.s) is used widely as a traditional medicine for the treatment of multiple ailments, including cancer in South East Asia. The present in vitro study was designed to investigate the complementary effects of an ethanolic extract of O.s (Et. O.s) or rosmarinic acid in combination with gemcitabine on Panc-1 pancreatic cancer cells.
Cell viability and colony formation assays were used to determine the 50% inhibitory concentration (IC50) of Et. O.s, rosmarinic acid, and gemcitabine. Different doses of gemcitabine in combination with Et. O.s or rosmarinic acid were tested against Panc-1 to select the best concentrations which possessed synergistic effects. Elucidation of molecular mechanisms responsible for mediating chemo-sensitivity in Panc-1 was performed using Quantitative Real-time PCR (QPCR), flow cytometry and immunohistochemistry.
Et. O.s was found to significantly sensitise Panc-1 towards gemcitabine by reducing the gene expression of multidrug-resistant protein family (MDR) (MDR-1, MRP-4, and MRP-5) and molecules related to epithelial-mesenchymal transition (ZEB-1 and Snail-1). An induction of the human equilibrate nucleoside transporter-1 (hENT-1) gene was also found in cells treated with Et. O.s-gemcitabine. The Et. O.s-gemcitabine combination induced cellular senescence, cell death and cell cycle arrest in Panc-1. In addition, the inhibition of Notch signalling was demonstrated through the downregulation of Notch 1 intracellular domain in this treatment group. In contrast, rosmarinic acid-gemcitabine combination showed no additional effects on cellular senescence, apoptosis, epithelial mesenchymal transition (EMT) markers, the MRP-4 and MRP-5 multi-drug resistance protein family, hENT-1, and the Notch pathway through Notch 1 intracellular domain.
This study provides valuable insights on the use of Et. O.s to complement gemcitabine in targeting pancreatic cancer in vitro, suggesting its potential use as a novel complementary treatment in pancreatic cancer patients.
[Display omitted] |
| doi_str_mv | 10.1016/j.bj.2020.05.015 |
| format | Article |
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Cell viability and colony formation assays were used to determine the 50% inhibitory concentration (IC50) of Et. O.s, rosmarinic acid, and gemcitabine. Different doses of gemcitabine in combination with Et. O.s or rosmarinic acid were tested against Panc-1 to select the best concentrations which possessed synergistic effects. Elucidation of molecular mechanisms responsible for mediating chemo-sensitivity in Panc-1 was performed using Quantitative Real-time PCR (QPCR), flow cytometry and immunohistochemistry.
Et. O.s was found to significantly sensitise Panc-1 towards gemcitabine by reducing the gene expression of multidrug-resistant protein family (MDR) (MDR-1, MRP-4, and MRP-5) and molecules related to epithelial-mesenchymal transition (ZEB-1 and Snail-1). An induction of the human equilibrate nucleoside transporter-1 (hENT-1) gene was also found in cells treated with Et. O.s-gemcitabine. The Et. O.s-gemcitabine combination induced cellular senescence, cell death and cell cycle arrest in Panc-1. In addition, the inhibition of Notch signalling was demonstrated through the downregulation of Notch 1 intracellular domain in this treatment group. In contrast, rosmarinic acid-gemcitabine combination showed no additional effects on cellular senescence, apoptosis, epithelial mesenchymal transition (EMT) markers, the MRP-4 and MRP-5 multi-drug resistance protein family, hENT-1, and the Notch pathway through Notch 1 intracellular domain.
This study provides valuable insights on the use of Et. O.s to complement gemcitabine in targeting pancreatic cancer in vitro, suggesting its potential use as a novel complementary treatment in pancreatic cancer patients.
[Display omitted]</description><identifier>ISSN: 2319-4170</identifier><identifier>EISSN: 2320-2890</identifier><identifier>DOI: 10.1016/j.bj.2020.05.015</identifier><identifier>PMID: 35166208</identifier><language>eng</language><publisher>AMSTERDAM: Elsevier B.V</publisher><subject><![CDATA[Apoptosis ; Biochemistry & Molecular Biology ; Cell Line, Tumor ; Cinnamates ; Complementary medicine ; Deoxycytidine - analogs & derivatives ; Depsides ; Gemcitabine ; Humans ; Life Sciences & Biomedicine ; Medicine, Research & Experimental ; Original ; Orthosiphon - chemistry ; Orthosiphon stamineus ; Pancreatic cancer ; Pancreatic Neoplasms - drug therapy ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - pathology ; Plant Extracts - pharmacology ; Plant Extracts - therapeutic use ; Research & Experimental Medicine ; Rosmarinic Acid ; Science & Technology]]></subject><ispartof>Biomedical Journal, 2021-12, Vol.44 (6), p.694-708</ispartof><rights>2020 Chang Gung University</rights><rights>Copyright © 2020 Chang Gung University. Published by Elsevier B.V. All rights reserved.</rights><rights>2020 Chang Gung University. Publishing services by Elsevier B.V. 2020 Chang Gung University</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>10</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000754493100008</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c447t-3bcbf5113c47292d2cccc871ddf59e8b1f4c641fc9f3393470cbe02096a5a793</citedby><cites>FETCH-LOGICAL-c447t-3bcbf5113c47292d2cccc871ddf59e8b1f4c641fc9f3393470cbe02096a5a793</cites><orcidid>0000-0001-8989-9945</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8847836/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8847836/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2115,27929,27930,39263,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35166208$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yehya, Ashwaq H.S.</creatorcontrib><creatorcontrib>Asif, Muhammad</creatorcontrib><creatorcontrib>Abdul Majid, Amin M.S.</creatorcontrib><creatorcontrib>Oon, Chern E.</creatorcontrib><title>Complementary effects of Orthosiphon stamineus standardized ethanolic extract and rosmarinic acid in combination with gemcitabine on pancreatic cancer</title><title>Biomedical Journal</title><addtitle>BIOMED J</addtitle><addtitle>Biomed J</addtitle><description>Pancreatic cancer is one of the most notorious cancers and is known for its highly invasive characteristics, drug resistance, and metastatic progression. Unfortunately, many patients with advanced pancreatic cancer become insensitive towards gemcitabine treatment. Orthosiphon stamineus (O.s) is used widely as a traditional medicine for the treatment of multiple ailments, including cancer in South East Asia. The present in vitro study was designed to investigate the complementary effects of an ethanolic extract of O.s (Et. O.s) or rosmarinic acid in combination with gemcitabine on Panc-1 pancreatic cancer cells.
Cell viability and colony formation assays were used to determine the 50% inhibitory concentration (IC50) of Et. O.s, rosmarinic acid, and gemcitabine. Different doses of gemcitabine in combination with Et. O.s or rosmarinic acid were tested against Panc-1 to select the best concentrations which possessed synergistic effects. Elucidation of molecular mechanisms responsible for mediating chemo-sensitivity in Panc-1 was performed using Quantitative Real-time PCR (QPCR), flow cytometry and immunohistochemistry.
Et. O.s was found to significantly sensitise Panc-1 towards gemcitabine by reducing the gene expression of multidrug-resistant protein family (MDR) (MDR-1, MRP-4, and MRP-5) and molecules related to epithelial-mesenchymal transition (ZEB-1 and Snail-1). An induction of the human equilibrate nucleoside transporter-1 (hENT-1) gene was also found in cells treated with Et. O.s-gemcitabine. The Et. O.s-gemcitabine combination induced cellular senescence, cell death and cell cycle arrest in Panc-1. In addition, the inhibition of Notch signalling was demonstrated through the downregulation of Notch 1 intracellular domain in this treatment group. In contrast, rosmarinic acid-gemcitabine combination showed no additional effects on cellular senescence, apoptosis, epithelial mesenchymal transition (EMT) markers, the MRP-4 and MRP-5 multi-drug resistance protein family, hENT-1, and the Notch pathway through Notch 1 intracellular domain.
This study provides valuable insights on the use of Et. O.s to complement gemcitabine in targeting pancreatic cancer in vitro, suggesting its potential use as a novel complementary treatment in pancreatic cancer patients.
[Display omitted]</description><subject>Apoptosis</subject><subject>Biochemistry & Molecular Biology</subject><subject>Cell Line, Tumor</subject><subject>Cinnamates</subject><subject>Complementary medicine</subject><subject>Deoxycytidine - analogs & derivatives</subject><subject>Depsides</subject><subject>Gemcitabine</subject><subject>Humans</subject><subject>Life Sciences & Biomedicine</subject><subject>Medicine, Research & Experimental</subject><subject>Original</subject><subject>Orthosiphon - chemistry</subject><subject>Orthosiphon stamineus</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - drug therapy</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Plant Extracts - pharmacology</subject><subject>Plant Extracts - therapeutic use</subject><subject>Research & Experimental Medicine</subject><subject>Rosmarinic Acid</subject><subject>Science & Technology</subject><issn>2319-4170</issn><issn>2320-2890</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>HGBXW</sourceid><sourceid>EIF</sourceid><recordid>eNqNUsuKFTEQbURxhnH2riRLQbpN0m8XgjS-YGA2sw_ppDKdS3fSJrnz8EP8Xqu914suBLNJUXXOqVSdZNlLRgtGWfN2V4y7glNOC1oXlNVPsnNecprzrqdPt5j1ecVaepZdxmhHWlVtyRrePc_Oypo1DafdefZj8Ms6wwIuyfBIwBhQKRJvyHVIk492nbwjMcnFOtjHLXJaBm2_gyaQJun8bBWBhxSkSgSLJPi4yGAdpqWymlhHlF9G62SyqHVv00RuYVE2SUwCwdwqnQqAdUUUhhBeZM-MnCNcHu-L7ObTx5vhS351_fnr8OEqVzhNystRjaZmrFRVy3uuucLTtUxrU_fQjcxUqqmYUb0py76sWqpGwI31jaxl25cX2fuD7LofF9AKtxDkLNZgcYJH4aUVf1ecncStvxNdV7Vd2aDA66NA8N_2EJNYbFQwz9KB30fBG97TukcrEEoPUIULigHMqQ2jYjNU7MS4E5uhgtYCDUXKqz-fdyL8tg8Bbw6Aexi9icoCLu8Eo5S2dVVhd4x-obv_Rw9oz-bX4PcuIfXdgQpoxp2FII50bQN-GKG9_fcYPwFHY9Zn</recordid><startdate>20211201</startdate><enddate>20211201</enddate><creator>Yehya, Ashwaq H.S.</creator><creator>Asif, Muhammad</creator><creator>Abdul Majid, Amin M.S.</creator><creator>Oon, Chern E.</creator><general>Elsevier B.V</general><general>Elsevier</general><general>Chang Gung University</general><scope>6I.</scope><scope>AAFTH</scope><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</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>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8989-9945</orcidid></search><sort><creationdate>20211201</creationdate><title>Complementary effects of Orthosiphon stamineus standardized ethanolic extract and rosmarinic acid in combination with gemcitabine on pancreatic cancer</title><author>Yehya, Ashwaq H.S. ; Asif, Muhammad ; Abdul Majid, Amin M.S. ; Oon, Chern E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c447t-3bcbf5113c47292d2cccc871ddf59e8b1f4c641fc9f3393470cbe02096a5a793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Apoptosis</topic><topic>Biochemistry & Molecular Biology</topic><topic>Cell Line, Tumor</topic><topic>Cinnamates</topic><topic>Complementary medicine</topic><topic>Deoxycytidine - analogs & derivatives</topic><topic>Depsides</topic><topic>Gemcitabine</topic><topic>Humans</topic><topic>Life Sciences & Biomedicine</topic><topic>Medicine, Research & Experimental</topic><topic>Original</topic><topic>Orthosiphon - chemistry</topic><topic>Orthosiphon stamineus</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - drug therapy</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Plant Extracts - pharmacology</topic><topic>Plant Extracts - therapeutic use</topic><topic>Research & Experimental Medicine</topic><topic>Rosmarinic Acid</topic><topic>Science & Technology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yehya, Ashwaq H.S.</creatorcontrib><creatorcontrib>Asif, Muhammad</creatorcontrib><creatorcontrib>Abdul Majid, Amin M.S.</creatorcontrib><creatorcontrib>Oon, Chern E.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Web of Science - Science Citation Index Expanded - 2021</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biomedical Journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yehya, Ashwaq H.S.</au><au>Asif, Muhammad</au><au>Abdul Majid, Amin M.S.</au><au>Oon, Chern E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Complementary effects of Orthosiphon stamineus standardized ethanolic extract and rosmarinic acid in combination with gemcitabine on pancreatic cancer</atitle><jtitle>Biomedical Journal</jtitle><stitle>BIOMED J</stitle><addtitle>Biomed J</addtitle><date>2021-12-01</date><risdate>2021</risdate><volume>44</volume><issue>6</issue><spage>694</spage><epage>708</epage><pages>694-708</pages><issn>2319-4170</issn><eissn>2320-2890</eissn><abstract>Pancreatic cancer is one of the most notorious cancers and is known for its highly invasive characteristics, drug resistance, and metastatic progression. Unfortunately, many patients with advanced pancreatic cancer become insensitive towards gemcitabine treatment. Orthosiphon stamineus (O.s) is used widely as a traditional medicine for the treatment of multiple ailments, including cancer in South East Asia. The present in vitro study was designed to investigate the complementary effects of an ethanolic extract of O.s (Et. O.s) or rosmarinic acid in combination with gemcitabine on Panc-1 pancreatic cancer cells.
Cell viability and colony formation assays were used to determine the 50% inhibitory concentration (IC50) of Et. O.s, rosmarinic acid, and gemcitabine. Different doses of gemcitabine in combination with Et. O.s or rosmarinic acid were tested against Panc-1 to select the best concentrations which possessed synergistic effects. Elucidation of molecular mechanisms responsible for mediating chemo-sensitivity in Panc-1 was performed using Quantitative Real-time PCR (QPCR), flow cytometry and immunohistochemistry.
Et. O.s was found to significantly sensitise Panc-1 towards gemcitabine by reducing the gene expression of multidrug-resistant protein family (MDR) (MDR-1, MRP-4, and MRP-5) and molecules related to epithelial-mesenchymal transition (ZEB-1 and Snail-1). An induction of the human equilibrate nucleoside transporter-1 (hENT-1) gene was also found in cells treated with Et. O.s-gemcitabine. The Et. O.s-gemcitabine combination induced cellular senescence, cell death and cell cycle arrest in Panc-1. In addition, the inhibition of Notch signalling was demonstrated through the downregulation of Notch 1 intracellular domain in this treatment group. In contrast, rosmarinic acid-gemcitabine combination showed no additional effects on cellular senescence, apoptosis, epithelial mesenchymal transition (EMT) markers, the MRP-4 and MRP-5 multi-drug resistance protein family, hENT-1, and the Notch pathway through Notch 1 intracellular domain.
This study provides valuable insights on the use of Et. O.s to complement gemcitabine in targeting pancreatic cancer in vitro, suggesting its potential use as a novel complementary treatment in pancreatic cancer patients.
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| subjects | Apoptosis Biochemistry & Molecular Biology Cell Line, Tumor Cinnamates Complementary medicine Deoxycytidine - analogs & derivatives Depsides Gemcitabine Humans Life Sciences & Biomedicine Medicine, Research & Experimental Original Orthosiphon - chemistry Orthosiphon stamineus Pancreatic cancer Pancreatic Neoplasms - drug therapy Pancreatic Neoplasms - genetics Pancreatic Neoplasms - pathology Plant Extracts - pharmacology Plant Extracts - therapeutic use Research & Experimental Medicine Rosmarinic Acid Science & Technology |
| title | Complementary effects of Orthosiphon stamineus standardized ethanolic extract and rosmarinic acid in combination with gemcitabine on pancreatic cancer |
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