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In vitro 3D colon tumor penetrability of SRJ09, a new anti-cancer andrographolide analog

Limited tumor penetrability of anti-cancer drugs is recognized as one of the major factors that lead to poor anti-tumor activity. SRJ09 (3,19-(2-bromobenzylidene) andrographolide) has been identified as a lead anti-cancer agent for colon cancer. Recently, this compound was shown by us to be a mutant...

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Main Authors: Wong, Charng Choon, Periasamy, Nagarajan, Sagineedu, Sreenivasa Rao, Mohd Sidik, Shiran, Sumon, Md. Shariful Hasan, Loadman, Paul, Phillips, Roger, Lajis, Md. Nordin, Stanslas, Johnson
Format: Article
Language:English
Published: Springer 2014
Online Access:http://psasir.upm.edu.my/id/eprint/37996/1/In%20vitro%203D%20colon%20tumor%20penetrability%20of%20SRJ09%2C%20a%20new%20anti-cancer%20andrographolide%20analog.pdf
http://psasir.upm.edu.my/id/eprint/37996/
http://link.springer.com/article/10.1007%2Fs10637-014-0105-6
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spelling my.upm.eprints.379962015-12-29T08:55:13Z http://psasir.upm.edu.my/id/eprint/37996/ In vitro 3D colon tumor penetrability of SRJ09, a new anti-cancer andrographolide analog Wong, Charng Choon Periasamy, Nagarajan Sagineedu, Sreenivasa Rao Mohd Sidik, Shiran Sumon, Md. Shariful Hasan Loadman, Paul Phillips, Roger Lajis, Md. Nordin Stanslas, Johnson Limited tumor penetrability of anti-cancer drugs is recognized as one of the major factors that lead to poor anti-tumor activity. SRJ09 (3,19-(2-bromobenzylidene) andrographolide) has been identified as a lead anti-cancer agent for colon cancer. Recently, this compound was shown by us to be a mutant K-Ras binder. In this present study, the penetrability of SRJ09 through the DLD-1 colon cancer multicell layer (MCL) was evaluated. The amount of SRJ09 that penetrated through the MCL was quantitated by utilizing high performance liquid chromatography (HPLC). Histopathological staining was used to visualize the morphology of MCL. A chemosensitivity assay was performed to assess the anti-cancer activity of SRJ09 in DLD-1 cells. SRJ09 was able to penetrate through DLD-1 MCL and is inversely proportional with the MCL thickness. The flow rates for SRJ09 through MCL were 0.90 ± 0.20 μM/min/cm2 and 0.56 ± 0.06 μM/min/cm2 for days 1 and 5, respectively, which are better than doxorubicin. Histopathological examination revealed that the integrity of the DLD-1 MCL was retained and no visible damage was inflicted on the cell membrane, confirming the penetration of SRJ09 was by diffusion. Short term exposure (1 h) in DLD-1 cells demonstrated SRJ09 had IC50 of 41 μM which was approximately 4-folds lower than andrographolide, the parent compound of SRJ09. In conclusion, SRJ09 successfully penetrated through DLD-1 MCL by diffusion and emerged as a potential candidate to be developed as a clinically viable anti-colon cancer drug. Springer 2014-10 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/37996/1/In%20vitro%203D%20colon%20tumor%20penetrability%20of%20SRJ09%2C%20a%20new%20anti-cancer%20andrographolide%20analog.pdf Wong, Charng Choon and Periasamy, Nagarajan and Sagineedu, Sreenivasa Rao and Mohd Sidik, Shiran and Sumon, Md. Shariful Hasan and Loadman, Paul and Phillips, Roger and Lajis, Md. Nordin and Stanslas, Johnson (2014) In vitro 3D colon tumor penetrability of SRJ09, a new anti-cancer andrographolide analog. Investigational New Drugs, 32 (5). pp. 806-814. ISSN 0167-6997; ESSN: 1573-0646 http://link.springer.com/article/10.1007%2Fs10637-014-0105-6 10.1007/s10637-014-0105-6
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
language English
description Limited tumor penetrability of anti-cancer drugs is recognized as one of the major factors that lead to poor anti-tumor activity. SRJ09 (3,19-(2-bromobenzylidene) andrographolide) has been identified as a lead anti-cancer agent for colon cancer. Recently, this compound was shown by us to be a mutant K-Ras binder. In this present study, the penetrability of SRJ09 through the DLD-1 colon cancer multicell layer (MCL) was evaluated. The amount of SRJ09 that penetrated through the MCL was quantitated by utilizing high performance liquid chromatography (HPLC). Histopathological staining was used to visualize the morphology of MCL. A chemosensitivity assay was performed to assess the anti-cancer activity of SRJ09 in DLD-1 cells. SRJ09 was able to penetrate through DLD-1 MCL and is inversely proportional with the MCL thickness. The flow rates for SRJ09 through MCL were 0.90 ± 0.20 μM/min/cm2 and 0.56 ± 0.06 μM/min/cm2 for days 1 and 5, respectively, which are better than doxorubicin. Histopathological examination revealed that the integrity of the DLD-1 MCL was retained and no visible damage was inflicted on the cell membrane, confirming the penetration of SRJ09 was by diffusion. Short term exposure (1 h) in DLD-1 cells demonstrated SRJ09 had IC50 of 41 μM which was approximately 4-folds lower than andrographolide, the parent compound of SRJ09. In conclusion, SRJ09 successfully penetrated through DLD-1 MCL by diffusion and emerged as a potential candidate to be developed as a clinically viable anti-colon cancer drug.
format Article
author Wong, Charng Choon
Periasamy, Nagarajan
Sagineedu, Sreenivasa Rao
Mohd Sidik, Shiran
Sumon, Md. Shariful Hasan
Loadman, Paul
Phillips, Roger
Lajis, Md. Nordin
Stanslas, Johnson
spellingShingle Wong, Charng Choon
Periasamy, Nagarajan
Sagineedu, Sreenivasa Rao
Mohd Sidik, Shiran
Sumon, Md. Shariful Hasan
Loadman, Paul
Phillips, Roger
Lajis, Md. Nordin
Stanslas, Johnson
In vitro 3D colon tumor penetrability of SRJ09, a new anti-cancer andrographolide analog
author_facet Wong, Charng Choon
Periasamy, Nagarajan
Sagineedu, Sreenivasa Rao
Mohd Sidik, Shiran
Sumon, Md. Shariful Hasan
Loadman, Paul
Phillips, Roger
Lajis, Md. Nordin
Stanslas, Johnson
author_sort Wong, Charng Choon
title In vitro 3D colon tumor penetrability of SRJ09, a new anti-cancer andrographolide analog
title_short In vitro 3D colon tumor penetrability of SRJ09, a new anti-cancer andrographolide analog
title_full In vitro 3D colon tumor penetrability of SRJ09, a new anti-cancer andrographolide analog
title_fullStr In vitro 3D colon tumor penetrability of SRJ09, a new anti-cancer andrographolide analog
title_full_unstemmed In vitro 3D colon tumor penetrability of SRJ09, a new anti-cancer andrographolide analog
title_sort in vitro 3d colon tumor penetrability of srj09, a new anti-cancer andrographolide analog
publisher Springer
publishDate 2014
url http://psasir.upm.edu.my/id/eprint/37996/1/In%20vitro%203D%20colon%20tumor%20penetrability%20of%20SRJ09%2C%20a%20new%20anti-cancer%20andrographolide%20analog.pdf
http://psasir.upm.edu.my/id/eprint/37996/
http://link.springer.com/article/10.1007%2Fs10637-014-0105-6
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score 13.211869

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