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Functional Component Isolated from Phaseolus vulgaris Lectin Exerts In Vitro and In Vivo Anti-Tumor Activity Through Potentiation of Apoptosis and Immunomodulation
Phytohemagglutinin (PHA), the lectin purified from red kidney bean (Phaseolus vulgaris), is a well-known mitogen for human lymphocyte. Because it has obvious anti-proliferative and anti-tumor activity, PHA may serve as a potential antineoplastic drug in future cancer therapeutics. However, the liter...
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Published in: | Molecules (Basel, Switzerland) Switzerland), 2021-01, Vol.26 (2), p.498 |
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description | Phytohemagglutinin (PHA), the lectin purified from red kidney bean (Phaseolus vulgaris), is a well-known mitogen for human lymphocyte. Because it has obvious anti-proliferative and anti-tumor activity, PHA may serve as a potential antineoplastic drug in future cancer therapeutics. However, the literature is also replete with data on detrimental effects of PHA including oral toxicity, hemagglutinating activity, and immunogenicity. There is a critical need to evaluate the functional as well as the toxic components of PHAs to assist the rational designs of treatment with it. In this report, we performed SDS-PAGE to identify components of PHA-L, the tetrameric isomer of PHA with four identical L-type subunits, and then characterized biological function or toxicity of the major protein bands through in vitro experiments. It was found that the protein appearing as a 130 kD band in SDS-PAGE gel run under the condition of removal of β-mercaptoethanol from the sample buffer together with omission of a heating step could inhibit tumor cell growth and stimulate lymphocyte proliferation, while most of the 35 kD proteins are likely non-functional impurity proteins and 15 kD protein may be related to hemolytic effect. Importantly, the 130 kD functional protein exhibits promising in vivo anti-tumor activity in B16-F10 melanoma C57 BL/6 mouse models, which may be achieved through potentiation of apoptosis and immunomodulation. Altogether, our results suggest that PHA-L prepared from crude extracts of red kidney bean by standard strategies is a mixture of many ingredients, and a 130 kD protein of PHA-L was purified and identified as the major functional component. Our study may pave the way for PHA-L as a potential anticancer drug. |
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Because it has obvious anti-proliferative and anti-tumor activity, PHA may serve as a potential antineoplastic drug in future cancer therapeutics. However, the literature is also replete with data on detrimental effects of PHA including oral toxicity, hemagglutinating activity, and immunogenicity. There is a critical need to evaluate the functional as well as the toxic components of PHAs to assist the rational designs of treatment with it. In this report, we performed SDS-PAGE to identify components of PHA-L, the tetrameric isomer of PHA with four identical L-type subunits, and then characterized biological function or toxicity of the major protein bands through in vitro experiments. It was found that the protein appearing as a 130 kD band in SDS-PAGE gel run under the condition of removal of β-mercaptoethanol from the sample buffer together with omission of a heating step could inhibit tumor cell growth and stimulate lymphocyte proliferation, while most of the 35 kD proteins are likely non-functional impurity proteins and 15 kD protein may be related to hemolytic effect. Importantly, the 130 kD functional protein exhibits promising in vivo anti-tumor activity in B16-F10 melanoma C57 BL/6 mouse models, which may be achieved through potentiation of apoptosis and immunomodulation. Altogether, our results suggest that PHA-L prepared from crude extracts of red kidney bean by standard strategies is a mixture of many ingredients, and a 130 kD protein of PHA-L was purified and identified as the major functional component. Our study may pave the way for PHA-L as a potential anticancer drug.</description><identifier>ISSN: 1420-3049</identifier><identifier>EISSN: 1420-3049</identifier><identifier>DOI: 10.3390/molecules26020498</identifier><identifier>PMID: 33477737</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Animal models ; anti-tumor activity ; Apoptosis ; Beans ; Biocompatibility ; Cancer ; functional component ; Gel electrophoresis ; Immunogenicity ; Immunomodulation ; Kidney beans ; Lectins ; Lymphocytes ; Melanoma ; PHA-L ; Phaseolus vulgaris ; Proteins ; Toxicity</subject><ispartof>Molecules (Basel, Switzerland), 2021-01, Vol.26 (2), p.498</ispartof><rights>2021. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c493t-7103143f13afbf43bcb1973a44f9e0f37adb81191e3fe1c4984beddd9af9f7993</citedby><cites>FETCH-LOGICAL-c493t-7103143f13afbf43bcb1973a44f9e0f37adb81191e3fe1c4984beddd9af9f7993</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2480030756/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2480030756?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25752,27923,27924,37011,44589,53790,53792,74897</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33477737$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Peipei</creatorcontrib><creatorcontrib>Leng, Xiaohong</creatorcontrib><creatorcontrib>Duan, Jiaqi</creatorcontrib><creatorcontrib>Zhu, Yue</creatorcontrib><creatorcontrib>Wang, Jue</creatorcontrib><creatorcontrib>Yan, Zirui</creatorcontrib><creatorcontrib>Min, Shitong</creatorcontrib><creatorcontrib>Wei, Dapeng</creatorcontrib><creatorcontrib>Wang, Xia</creatorcontrib><title>Functional Component Isolated from Phaseolus vulgaris Lectin Exerts In Vitro and In Vivo Anti-Tumor Activity Through Potentiation of Apoptosis and Immunomodulation</title><title>Molecules (Basel, Switzerland)</title><addtitle>Molecules</addtitle><description>Phytohemagglutinin (PHA), the lectin purified from red kidney bean (Phaseolus vulgaris), is a well-known mitogen for human lymphocyte. Because it has obvious anti-proliferative and anti-tumor activity, PHA may serve as a potential antineoplastic drug in future cancer therapeutics. However, the literature is also replete with data on detrimental effects of PHA including oral toxicity, hemagglutinating activity, and immunogenicity. There is a critical need to evaluate the functional as well as the toxic components of PHAs to assist the rational designs of treatment with it. In this report, we performed SDS-PAGE to identify components of PHA-L, the tetrameric isomer of PHA with four identical L-type subunits, and then characterized biological function or toxicity of the major protein bands through in vitro experiments. It was found that the protein appearing as a 130 kD band in SDS-PAGE gel run under the condition of removal of β-mercaptoethanol from the sample buffer together with omission of a heating step could inhibit tumor cell growth and stimulate lymphocyte proliferation, while most of the 35 kD proteins are likely non-functional impurity proteins and 15 kD protein may be related to hemolytic effect. Importantly, the 130 kD functional protein exhibits promising in vivo anti-tumor activity in B16-F10 melanoma C57 BL/6 mouse models, which may be achieved through potentiation of apoptosis and immunomodulation. Altogether, our results suggest that PHA-L prepared from crude extracts of red kidney bean by standard strategies is a mixture of many ingredients, and a 130 kD protein of PHA-L was purified and identified as the major functional component. Our study may pave the way for PHA-L as a potential anticancer drug.</description><subject>Animal models</subject><subject>anti-tumor activity</subject><subject>Apoptosis</subject><subject>Beans</subject><subject>Biocompatibility</subject><subject>Cancer</subject><subject>functional component</subject><subject>Gel electrophoresis</subject><subject>Immunogenicity</subject><subject>Immunomodulation</subject><subject>Kidney beans</subject><subject>Lectins</subject><subject>Lymphocytes</subject><subject>Melanoma</subject><subject>PHA-L</subject><subject>Phaseolus vulgaris</subject><subject>Proteins</subject><subject>Toxicity</subject><issn>1420-3049</issn><issn>1420-3049</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNplks1uEzEUhUcIREvhAdggS6wH7LETjzdIUdRCpEh0Edha9thOHM34Bv9E9Hl4UdykVK1Y2dc-5zv-uU3znuBPlAr8eYLRDmW0qZvjDjPRv2guCetwS2vx8sn8onmT0h7jjjAye91cUMo455RfNn9uShiyh6BGtITpAMGGjFYJRpWtQS7ChG53KlkYS0LHMm5V9AmtbTUFdP3bxpzQKqCfPkdAKphzcQS0CNm3mzJBRIsqPvp8hza7CGW7Q7eQa4xX98EIHFoc4JAhVfCJME0lwASmjCfF2-aVU2Oy7x7Gq-bHzfVm-a1df_-6Wi7W7cAEzS0nmBJGHaHKaceoHjQRnCrGnLDYUa6M7gkRxFJnSfX0TFtjjFBOOC4EvWpWZ64BtZeH6CcV7yQoL08LELdSxeyH0UqG6_v3SvduEGyOjRa9VtoIK9zMYc0r68uZdSh6smao141qfAZ9vhP8Tm7hKHlPu0qvgI8PgAi_ik1Z7qHE-k1JdqzHmGI-m1cVOauGCClF6x4TCJb3PSL_65Hq-fD0aI-Of01B_wIdqL-f</recordid><startdate>20210118</startdate><enddate>20210118</enddate><creator>Wang, Peipei</creator><creator>Leng, Xiaohong</creator><creator>Duan, Jiaqi</creator><creator>Zhu, Yue</creator><creator>Wang, Jue</creator><creator>Yan, Zirui</creator><creator>Min, Shitong</creator><creator>Wei, Dapeng</creator><creator>Wang, Xia</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20210118</creationdate><title>Functional Component Isolated from Phaseolus vulgaris Lectin Exerts In Vitro and In Vivo Anti-Tumor Activity Through Potentiation of Apoptosis and Immunomodulation</title><author>Wang, Peipei ; 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Because it has obvious anti-proliferative and anti-tumor activity, PHA may serve as a potential antineoplastic drug in future cancer therapeutics. However, the literature is also replete with data on detrimental effects of PHA including oral toxicity, hemagglutinating activity, and immunogenicity. There is a critical need to evaluate the functional as well as the toxic components of PHAs to assist the rational designs of treatment with it. In this report, we performed SDS-PAGE to identify components of PHA-L, the tetrameric isomer of PHA with four identical L-type subunits, and then characterized biological function or toxicity of the major protein bands through in vitro experiments. It was found that the protein appearing as a 130 kD band in SDS-PAGE gel run under the condition of removal of β-mercaptoethanol from the sample buffer together with omission of a heating step could inhibit tumor cell growth and stimulate lymphocyte proliferation, while most of the 35 kD proteins are likely non-functional impurity proteins and 15 kD protein may be related to hemolytic effect. Importantly, the 130 kD functional protein exhibits promising in vivo anti-tumor activity in B16-F10 melanoma C57 BL/6 mouse models, which may be achieved through potentiation of apoptosis and immunomodulation. Altogether, our results suggest that PHA-L prepared from crude extracts of red kidney bean by standard strategies is a mixture of many ingredients, and a 130 kD protein of PHA-L was purified and identified as the major functional component. Our study may pave the way for PHA-L as a potential anticancer drug.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>33477737</pmid><doi>10.3390/molecules26020498</doi><oa>free_for_read</oa></addata></record> |
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subjects | Animal models anti-tumor activity Apoptosis Beans Biocompatibility Cancer functional component Gel electrophoresis Immunogenicity Immunomodulation Kidney beans Lectins Lymphocytes Melanoma PHA-L Phaseolus vulgaris Proteins Toxicity |
title | Functional Component Isolated from Phaseolus vulgaris Lectin Exerts In Vitro and In Vivo Anti-Tumor Activity Through Potentiation of Apoptosis and Immunomodulation |
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