Cytotoxicity mechanisms of plumbagin in drug-resistant tongue squamous cell carcinoma
Abstract Objectives To evaluate the inhibitory effect and mechanism of plumbagin (PLB) against drug-resistant tongue squamous cell carcinoma (TSCC), and whether its antitumour effect is not affected by tumour drug resistance. Methods TSCC sensitive CAL27 cells and drug-resistant CAL27/RE cells were...
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| Veröffentlicht in: | Journal of pharmacy and pharmacology 2021-03, Vol.73 (1), p.98-109 |
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| creator | Xue, Danfeng Zhou, Xiongming Qiu, Jiaxuan |
| description | Abstract
Objectives
To evaluate the inhibitory effect and mechanism of plumbagin (PLB) against drug-resistant tongue squamous cell carcinoma (TSCC), and whether its antitumour effect is not affected by tumour drug resistance.
Methods
TSCC sensitive CAL27 cells and drug-resistant CAL27/RE cells were used to study the cytotoxicity and mechanism of PLB in vitro, including CCK-8 analysis, colony formation, DAPI staining, flow cytometry assay, transmission electron microscopy, western blotting assay, autophagy, apoptosis and ROS fluorescent probes. BALB/c nude mice xenograft models were used to study the growth inhibitory effect of PLB in vivo.
Key findings
The results showed that the cell viability and proliferation inhibition and apoptosis induction abilities of PLB on drug-resistant cells were more obvious than that on sensitive cells. And PLB induced protective autophagy in TSCC cells. Mechanistically, PLB induced apoptosis and autophagy by generating reactive oxygen species to mediate JNK and AKT/mTOR pathways. Finally, the growth inhibitory effect of PLB against drug-resistant TSCC was also confirmed in vivo.
Conclusions
PLB will be a promising anticancer agent to overcome drug-resistant TSCC without being affected by its drug resistance properties. |
| doi_str_mv | 10.1093/jpp/rgaa027 |
| format | Article |
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Objectives
To evaluate the inhibitory effect and mechanism of plumbagin (PLB) against drug-resistant tongue squamous cell carcinoma (TSCC), and whether its antitumour effect is not affected by tumour drug resistance.
Methods
TSCC sensitive CAL27 cells and drug-resistant CAL27/RE cells were used to study the cytotoxicity and mechanism of PLB in vitro, including CCK-8 analysis, colony formation, DAPI staining, flow cytometry assay, transmission electron microscopy, western blotting assay, autophagy, apoptosis and ROS fluorescent probes. BALB/c nude mice xenograft models were used to study the growth inhibitory effect of PLB in vivo.
Key findings
The results showed that the cell viability and proliferation inhibition and apoptosis induction abilities of PLB on drug-resistant cells were more obvious than that on sensitive cells. And PLB induced protective autophagy in TSCC cells. Mechanistically, PLB induced apoptosis and autophagy by generating reactive oxygen species to mediate JNK and AKT/mTOR pathways. Finally, the growth inhibitory effect of PLB against drug-resistant TSCC was also confirmed in vivo.
Conclusions
PLB will be a promising anticancer agent to overcome drug-resistant TSCC without being affected by its drug resistance properties.</description><identifier>ISSN: 0022-3573</identifier><identifier>EISSN: 2042-7158</identifier><identifier>DOI: 10.1093/jpp/rgaa027</identifier><identifier>PMID: 33791802</identifier><language>eng</language><publisher>UK: Oxford University Press</publisher><subject>Animals ; Antineoplastic Agents, Phytogenic - pharmacology ; Antineoplastic Agents, Phytogenic - therapeutic use ; Apoptosis ; Autophagy ; Carcinoma, Squamous Cell - drug therapy ; Carcinoma, Squamous Cell - metabolism ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Drug Resistance, Neoplasm - drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Naphthoquinones - pharmacology ; Naphthoquinones - therapeutic use ; Phytotherapy ; Plant Extracts - pharmacology ; Plant Extracts - therapeutic use ; Tongue - drug effects ; Tongue - metabolism ; Tongue - pathology ; Tongue Neoplasms - drug therapy ; Tongue Neoplasms - metabolism ; Tongue Neoplasms - pathology ; TOR Serine-Threonine Kinases - metabolism</subject><ispartof>Journal of pharmacy and pharmacology, 2021-03, Vol.73 (1), p.98-109</ispartof><rights>The Author(s) 2020. Published by Oxford University Press on behalf of Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2020</rights><rights>The Author(s) 2020. Published by Oxford University Press on behalf of Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-3e3a6cf2c4b2cbbb9492a7167318d72cef556f6ac5469ce48fd97e37eb20088a3</citedby><cites>FETCH-LOGICAL-c362t-3e3a6cf2c4b2cbbb9492a7167318d72cef556f6ac5469ce48fd97e37eb20088a3</cites><orcidid>0000-0002-4629-1785</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27904,27905</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33791802$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xue, Danfeng</creatorcontrib><creatorcontrib>Zhou, Xiongming</creatorcontrib><creatorcontrib>Qiu, Jiaxuan</creatorcontrib><title>Cytotoxicity mechanisms of plumbagin in drug-resistant tongue squamous cell carcinoma</title><title>Journal of pharmacy and pharmacology</title><addtitle>J Pharm Pharmacol</addtitle><description>Abstract
Objectives
To evaluate the inhibitory effect and mechanism of plumbagin (PLB) against drug-resistant tongue squamous cell carcinoma (TSCC), and whether its antitumour effect is not affected by tumour drug resistance.
Methods
TSCC sensitive CAL27 cells and drug-resistant CAL27/RE cells were used to study the cytotoxicity and mechanism of PLB in vitro, including CCK-8 analysis, colony formation, DAPI staining, flow cytometry assay, transmission electron microscopy, western blotting assay, autophagy, apoptosis and ROS fluorescent probes. BALB/c nude mice xenograft models were used to study the growth inhibitory effect of PLB in vivo.
Key findings
The results showed that the cell viability and proliferation inhibition and apoptosis induction abilities of PLB on drug-resistant cells were more obvious than that on sensitive cells. And PLB induced protective autophagy in TSCC cells. Mechanistically, PLB induced apoptosis and autophagy by generating reactive oxygen species to mediate JNK and AKT/mTOR pathways. Finally, the growth inhibitory effect of PLB against drug-resistant TSCC was also confirmed in vivo.
Conclusions
PLB will be a promising anticancer agent to overcome drug-resistant TSCC without being affected by its drug resistance properties.</description><subject>Animals</subject><subject>Antineoplastic Agents, Phytogenic - pharmacology</subject><subject>Antineoplastic Agents, Phytogenic - therapeutic use</subject><subject>Apoptosis</subject><subject>Autophagy</subject><subject>Carcinoma, Squamous Cell - drug therapy</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Cell Survival</subject><subject>Drug Resistance, Neoplasm - drug effects</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Naphthoquinones - pharmacology</subject><subject>Naphthoquinones - therapeutic use</subject><subject>Phytotherapy</subject><subject>Plant Extracts - pharmacology</subject><subject>Plant Extracts - therapeutic use</subject><subject>Tongue - drug effects</subject><subject>Tongue - metabolism</subject><subject>Tongue - pathology</subject><subject>Tongue Neoplasms - drug therapy</subject><subject>Tongue Neoplasms - metabolism</subject><subject>Tongue Neoplasms - pathology</subject><subject>TOR Serine-Threonine Kinases - metabolism</subject><issn>0022-3573</issn><issn>2042-7158</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1LwzAYh4Mobk5P3iUnEaQuH23SHmX4BQMv7lzSNK0ZTVPzAe6_N2PTo_DCe3l4-PEAcI3RA0YVXW6nael6IRDhJ2BOUE4yjovyFMwRIiSjBaczcOH9FiHEGWPnYEYpr3CJyBxsVrtgg_3WUocdNEp-ilF746Ht4DRE04hejzBd62KfOeW1D2IMMNixjwr6ryiMjR5KNQxQCif1aI24BGedGLy6Ov4F2Dw_faxes_X7y9vqcZ1JykjIqKKCyY7IvCGyaZoqr4jgmHGKy5YTqbqiYB0TsshZJVVedm3FFeWqIQiVpaALcHfwTs5-ReVDbbTfTxGjSqtqUiCeZJhUCb0_oNJZ753q6slpI9yuxqjed6xTx_rYMdE3R3FsjGr_2N9wCbg9ADZO_5p-AAMgfic</recordid><startdate>20210301</startdate><enddate>20210301</enddate><creator>Xue, Danfeng</creator><creator>Zhou, Xiongming</creator><creator>Qiu, Jiaxuan</creator><general>Oxford University Press</general><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><orcidid>https://orcid.org/0000-0002-4629-1785</orcidid></search><sort><creationdate>20210301</creationdate><title>Cytotoxicity mechanisms of plumbagin in drug-resistant tongue squamous cell carcinoma</title><author>Xue, Danfeng ; Zhou, Xiongming ; Qiu, Jiaxuan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-3e3a6cf2c4b2cbbb9492a7167318d72cef556f6ac5469ce48fd97e37eb20088a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Antineoplastic Agents, Phytogenic - pharmacology</topic><topic>Antineoplastic Agents, Phytogenic - therapeutic use</topic><topic>Apoptosis</topic><topic>Autophagy</topic><topic>Carcinoma, Squamous Cell - drug therapy</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Cell Survival</topic><topic>Drug Resistance, Neoplasm - drug effects</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Naphthoquinones - pharmacology</topic><topic>Naphthoquinones - therapeutic use</topic><topic>Phytotherapy</topic><topic>Plant Extracts - pharmacology</topic><topic>Plant Extracts - therapeutic use</topic><topic>Tongue - drug effects</topic><topic>Tongue - metabolism</topic><topic>Tongue - pathology</topic><topic>Tongue Neoplasms - drug therapy</topic><topic>Tongue Neoplasms - metabolism</topic><topic>Tongue Neoplasms - pathology</topic><topic>TOR Serine-Threonine Kinases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xue, Danfeng</creatorcontrib><creatorcontrib>Zhou, Xiongming</creatorcontrib><creatorcontrib>Qiu, Jiaxuan</creatorcontrib><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><jtitle>Journal of pharmacy and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xue, Danfeng</au><au>Zhou, Xiongming</au><au>Qiu, Jiaxuan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytotoxicity mechanisms of plumbagin in drug-resistant tongue squamous cell carcinoma</atitle><jtitle>Journal of pharmacy and pharmacology</jtitle><addtitle>J Pharm Pharmacol</addtitle><date>2021-03-01</date><risdate>2021</risdate><volume>73</volume><issue>1</issue><spage>98</spage><epage>109</epage><pages>98-109</pages><issn>0022-3573</issn><eissn>2042-7158</eissn><abstract>Abstract
Objectives
To evaluate the inhibitory effect and mechanism of plumbagin (PLB) against drug-resistant tongue squamous cell carcinoma (TSCC), and whether its antitumour effect is not affected by tumour drug resistance.
Methods
TSCC sensitive CAL27 cells and drug-resistant CAL27/RE cells were used to study the cytotoxicity and mechanism of PLB in vitro, including CCK-8 analysis, colony formation, DAPI staining, flow cytometry assay, transmission electron microscopy, western blotting assay, autophagy, apoptosis and ROS fluorescent probes. BALB/c nude mice xenograft models were used to study the growth inhibitory effect of PLB in vivo.
Key findings
The results showed that the cell viability and proliferation inhibition and apoptosis induction abilities of PLB on drug-resistant cells were more obvious than that on sensitive cells. And PLB induced protective autophagy in TSCC cells. Mechanistically, PLB induced apoptosis and autophagy by generating reactive oxygen species to mediate JNK and AKT/mTOR pathways. Finally, the growth inhibitory effect of PLB against drug-resistant TSCC was also confirmed in vivo.
Conclusions
PLB will be a promising anticancer agent to overcome drug-resistant TSCC without being affected by its drug resistance properties.</abstract><cop>UK</cop><pub>Oxford University Press</pub><pmid>33791802</pmid><doi>10.1093/jpp/rgaa027</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-4629-1785</orcidid></addata></record> |
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| subjects | Animals Antineoplastic Agents, Phytogenic - pharmacology Antineoplastic Agents, Phytogenic - therapeutic use Apoptosis Autophagy Carcinoma, Squamous Cell - drug therapy Carcinoma, Squamous Cell - metabolism Cell Line, Tumor Cell Proliferation Cell Survival Drug Resistance, Neoplasm - drug effects Male Mice Mice, Inbred BALB C Mice, Nude Naphthoquinones - pharmacology Naphthoquinones - therapeutic use Phytotherapy Plant Extracts - pharmacology Plant Extracts - therapeutic use Tongue - drug effects Tongue - metabolism Tongue - pathology Tongue Neoplasms - drug therapy Tongue Neoplasms - metabolism Tongue Neoplasms - pathology TOR Serine-Threonine Kinases - metabolism |
| title | Cytotoxicity mechanisms of plumbagin in drug-resistant tongue squamous cell carcinoma |
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