Anticancer effect of dentatin and dentatin-hydroxypropyl-P-cyclodextrin complex on human colon cancer cell line
Introduction: Dentatin (DEN) (5-methoxy-2, 2-dimethyl-10-(1, 1-dimethyl-2propenyl) dipyran-2-one), a natural compound present in the roots of Clausena excavata Burm f, possesses pro-apoptotic and antiproliferative effects in various cancer cells. Because of its hydrophobicity, it is believed that it...
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creator | AL-Abboodi, Ashwaq Shakir Rasedee, Abdullah Abdul, Ahmad Bustamam Taufiq-Yap, Yun Hin Alkaby, Wafaa Abd Alwahed Ghaji, Mostafa Saddam Waziri, Peter M Al-Qubaisi, Mothanna Sadiq |
description | Introduction: Dentatin (DEN) (5-methoxy-2, 2-dimethyl-10-(1, 1-dimethyl-2propenyl) dipyran-2-one), a natural compound present in the roots of Clausena excavata Burm f, possesses pro-apoptotic and antiproliferative effects in various cancer cells. Because of its hydrophobicity, it is believed that its complexation with hydroxy-[beta]-cyclodextrin (HP[beta]CD) will make it a potent inhibitor of cancer cell growth. In the current work, the molecular mechanisms of apoptosis induced by DEN and DEN-HP[beta]CD complex were demonstrated in human colon HT-29 cancer cells. Materials and methods: After the human colon HT-29 cancer cells were treated with DEN and DEN-HP[beta]CD complex, their effects on the expression of apoptotic-regulated gene markers in mitochondria-mediated apoptotic and death receptor pathways were detected by Western blot analysis and reverse transcription polymerase chain reaction. These markers included caspases-9, 3, and 8, cytochrome c, poly (ADP-ribose) polymerase, p53, p21, cyclin A as well as the Bcl-2 family of proteins. Results: At 3, 6, 12, and 24 [micro]g/mL exposure, DEN and DEN-HP[beta]CD complex significantly affected apoptosis in HT-29 cells through the down-regulation of Bcl-2 and cyclin A in turn, and up-regulation of Bax, p53, p21, cytochrome c at both protein and mRNA levels. DEN and DEN-HP[beta]CD complex also decreased cleaved poly (ADP-ribose) polymerase and induced caspases-3, -8, and -9. Conclusion: Results of this study indicate that the apoptotic pathway caused by DEN and DEN-HP[beta]CD complex are mediated by the regulation of caspases and Bcl-2 families in human colon HT-29 cancer cells. The results also suggest that DEN-HP[beta]CD complex may have chemotherapeutic benefits for colon cancer patients. Keywords: natural products, HP[beta]CD, apoptosis, pro-apoptotic proteins, anti-apoptotic proteins |
doi_str_mv | 10.2147/DDDT.SI47626 |
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Because of its hydrophobicity, it is believed that its complexation with hydroxy-[beta]-cyclodextrin (HP[beta]CD) will make it a potent inhibitor of cancer cell growth. In the current work, the molecular mechanisms of apoptosis induced by DEN and DEN-HP[beta]CD complex were demonstrated in human colon HT-29 cancer cells. Materials and methods: After the human colon HT-29 cancer cells were treated with DEN and DEN-HP[beta]CD complex, their effects on the expression of apoptotic-regulated gene markers in mitochondria-mediated apoptotic and death receptor pathways were detected by Western blot analysis and reverse transcription polymerase chain reaction. These markers included caspases-9, 3, and 8, cytochrome c, poly (ADP-ribose) polymerase, p53, p21, cyclin A as well as the Bcl-2 family of proteins. Results: At 3, 6, 12, and 24 [micro]g/mL exposure, DEN and DEN-HP[beta]CD complex significantly affected apoptosis in HT-29 cells through the down-regulation of Bcl-2 and cyclin A in turn, and up-regulation of Bax, p53, p21, cytochrome c at both protein and mRNA levels. DEN and DEN-HP[beta]CD complex also decreased cleaved poly (ADP-ribose) polymerase and induced caspases-3, -8, and -9. Conclusion: Results of this study indicate that the apoptotic pathway caused by DEN and DEN-HP[beta]CD complex are mediated by the regulation of caspases and Bcl-2 families in human colon HT-29 cancer cells. The results also suggest that DEN-HP[beta]CD complex may have chemotherapeutic benefits for colon cancer patients. Keywords: natural products, HP[beta]CD, apoptosis, pro-apoptotic proteins, anti-apoptotic proteins</description><identifier>ISSN: 1177-8881</identifier><identifier>EISSN: 1177-8881</identifier><identifier>DOI: 10.2147/DDDT.SI47626</identifier><language>eng</language><publisher>Dove Medical Press Limited</publisher><subject>Apoptosis ; Cell lines ; Colon cancer ; Cyclodextrins</subject><ispartof>Drug design, development and therapy, 2017-01, Vol.11, p.3309</ispartof><rights>COPYRIGHT 2017 Dove Medical Press Limited</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,864,27924,27925</link.rule.ids></links><search><creatorcontrib>AL-Abboodi, Ashwaq Shakir</creatorcontrib><creatorcontrib>Rasedee, Abdullah</creatorcontrib><creatorcontrib>Abdul, Ahmad Bustamam</creatorcontrib><creatorcontrib>Taufiq-Yap, Yun Hin</creatorcontrib><creatorcontrib>Alkaby, Wafaa Abd Alwahed</creatorcontrib><creatorcontrib>Ghaji, Mostafa Saddam</creatorcontrib><creatorcontrib>Waziri, Peter M</creatorcontrib><creatorcontrib>Al-Qubaisi, Mothanna Sadiq</creatorcontrib><title>Anticancer effect of dentatin and dentatin-hydroxypropyl-P-cyclodextrin complex on human colon cancer cell line</title><title>Drug design, development and therapy</title><description>Introduction: Dentatin (DEN) (5-methoxy-2, 2-dimethyl-10-(1, 1-dimethyl-2propenyl) dipyran-2-one), a natural compound present in the roots of Clausena excavata Burm f, possesses pro-apoptotic and antiproliferative effects in various cancer cells. Because of its hydrophobicity, it is believed that its complexation with hydroxy-[beta]-cyclodextrin (HP[beta]CD) will make it a potent inhibitor of cancer cell growth. In the current work, the molecular mechanisms of apoptosis induced by DEN and DEN-HP[beta]CD complex were demonstrated in human colon HT-29 cancer cells. Materials and methods: After the human colon HT-29 cancer cells were treated with DEN and DEN-HP[beta]CD complex, their effects on the expression of apoptotic-regulated gene markers in mitochondria-mediated apoptotic and death receptor pathways were detected by Western blot analysis and reverse transcription polymerase chain reaction. These markers included caspases-9, 3, and 8, cytochrome c, poly (ADP-ribose) polymerase, p53, p21, cyclin A as well as the Bcl-2 family of proteins. Results: At 3, 6, 12, and 24 [micro]g/mL exposure, DEN and DEN-HP[beta]CD complex significantly affected apoptosis in HT-29 cells through the down-regulation of Bcl-2 and cyclin A in turn, and up-regulation of Bax, p53, p21, cytochrome c at both protein and mRNA levels. DEN and DEN-HP[beta]CD complex also decreased cleaved poly (ADP-ribose) polymerase and induced caspases-3, -8, and -9. Conclusion: Results of this study indicate that the apoptotic pathway caused by DEN and DEN-HP[beta]CD complex are mediated by the regulation of caspases and Bcl-2 families in human colon HT-29 cancer cells. The results also suggest that DEN-HP[beta]CD complex may have chemotherapeutic benefits for colon cancer patients. Keywords: natural products, HP[beta]CD, apoptosis, pro-apoptotic proteins, anti-apoptotic proteins</description><subject>Apoptosis</subject><subject>Cell lines</subject><subject>Colon cancer</subject><subject>Cyclodextrins</subject><issn>1177-8881</issn><issn>1177-8881</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid/><recordid>eNptj0trwzAQhEVpoWnaW3-AoWelkm09fAxJH4FAC809yKtVoiJLwXYh_vd1aSg5lD3szPDtwBJyz9ks56V6XC6Xm9nHqlQylxdkwrlSVGvNL8_0Nbnpuk_GZCFzNiFpHnsPJgK2GTqH0GfJZRZjb3ofMxPtn6H7wbbpOBzadBgCfacwQEgWj307kpCaQ8BjlmK2_2rMTxBGfaoGDCELPuItuXImdHh32lOyeX7aLF7p-u1ltZiv6U4qQaE2oq5A66JCpXPlKgfcmYrVKGvlXMEZAFdWjo9qpjln0ggpcsOZ1bzUxZQ8_NbuTMCtjy71rYHGd7Cdi4JrXWohRmr2DzWOxcZDiuj8mJ8dfAO1MGvO</recordid><startdate>20170101</startdate><enddate>20170101</enddate><creator>AL-Abboodi, Ashwaq Shakir</creator><creator>Rasedee, Abdullah</creator><creator>Abdul, Ahmad Bustamam</creator><creator>Taufiq-Yap, Yun Hin</creator><creator>Alkaby, Wafaa Abd Alwahed</creator><creator>Ghaji, Mostafa Saddam</creator><creator>Waziri, Peter M</creator><creator>Al-Qubaisi, Mothanna Sadiq</creator><general>Dove Medical Press Limited</general><scope/></search><sort><creationdate>20170101</creationdate><title>Anticancer effect of dentatin and dentatin-hydroxypropyl-P-cyclodextrin complex on human colon cancer cell line</title><author>AL-Abboodi, Ashwaq Shakir ; Rasedee, Abdullah ; Abdul, Ahmad Bustamam ; Taufiq-Yap, Yun Hin ; Alkaby, Wafaa Abd Alwahed ; Ghaji, Mostafa Saddam ; Waziri, Peter M ; Al-Qubaisi, Mothanna Sadiq</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g675-cba5b9c8839e7827f9fc1fa90be6b7ff310cc17d66268081106a5652a10d81483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Apoptosis</topic><topic>Cell lines</topic><topic>Colon cancer</topic><topic>Cyclodextrins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>AL-Abboodi, Ashwaq Shakir</creatorcontrib><creatorcontrib>Rasedee, Abdullah</creatorcontrib><creatorcontrib>Abdul, Ahmad Bustamam</creatorcontrib><creatorcontrib>Taufiq-Yap, Yun Hin</creatorcontrib><creatorcontrib>Alkaby, Wafaa Abd Alwahed</creatorcontrib><creatorcontrib>Ghaji, Mostafa Saddam</creatorcontrib><creatorcontrib>Waziri, Peter M</creatorcontrib><creatorcontrib>Al-Qubaisi, Mothanna Sadiq</creatorcontrib><jtitle>Drug design, development and therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>AL-Abboodi, Ashwaq Shakir</au><au>Rasedee, Abdullah</au><au>Abdul, Ahmad Bustamam</au><au>Taufiq-Yap, Yun Hin</au><au>Alkaby, Wafaa Abd Alwahed</au><au>Ghaji, Mostafa Saddam</au><au>Waziri, Peter M</au><au>Al-Qubaisi, Mothanna Sadiq</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anticancer effect of dentatin and dentatin-hydroxypropyl-P-cyclodextrin complex on human colon cancer cell line</atitle><jtitle>Drug design, development and therapy</jtitle><date>2017-01-01</date><risdate>2017</risdate><volume>11</volume><spage>3309</spage><pages>3309-</pages><issn>1177-8881</issn><eissn>1177-8881</eissn><abstract>Introduction: Dentatin (DEN) (5-methoxy-2, 2-dimethyl-10-(1, 1-dimethyl-2propenyl) dipyran-2-one), a natural compound present in the roots of Clausena excavata Burm f, possesses pro-apoptotic and antiproliferative effects in various cancer cells. Because of its hydrophobicity, it is believed that its complexation with hydroxy-[beta]-cyclodextrin (HP[beta]CD) will make it a potent inhibitor of cancer cell growth. In the current work, the molecular mechanisms of apoptosis induced by DEN and DEN-HP[beta]CD complex were demonstrated in human colon HT-29 cancer cells. Materials and methods: After the human colon HT-29 cancer cells were treated with DEN and DEN-HP[beta]CD complex, their effects on the expression of apoptotic-regulated gene markers in mitochondria-mediated apoptotic and death receptor pathways were detected by Western blot analysis and reverse transcription polymerase chain reaction. These markers included caspases-9, 3, and 8, cytochrome c, poly (ADP-ribose) polymerase, p53, p21, cyclin A as well as the Bcl-2 family of proteins. Results: At 3, 6, 12, and 24 [micro]g/mL exposure, DEN and DEN-HP[beta]CD complex significantly affected apoptosis in HT-29 cells through the down-regulation of Bcl-2 and cyclin A in turn, and up-regulation of Bax, p53, p21, cytochrome c at both protein and mRNA levels. DEN and DEN-HP[beta]CD complex also decreased cleaved poly (ADP-ribose) polymerase and induced caspases-3, -8, and -9. Conclusion: Results of this study indicate that the apoptotic pathway caused by DEN and DEN-HP[beta]CD complex are mediated by the regulation of caspases and Bcl-2 families in human colon HT-29 cancer cells. The results also suggest that DEN-HP[beta]CD complex may have chemotherapeutic benefits for colon cancer patients. Keywords: natural products, HP[beta]CD, apoptosis, pro-apoptotic proteins, anti-apoptotic proteins</abstract><pub>Dove Medical Press Limited</pub><doi>10.2147/DDDT.SI47626</doi></addata></record> |
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subjects | Apoptosis Cell lines Colon cancer Cyclodextrins |
title | Anticancer effect of dentatin and dentatin-hydroxypropyl-P-cyclodextrin complex on human colon cancer cell line |
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