3, 3'-Diindolylmethane enhances the effectiveness of herceptin against HER-2/neu-expressing breast cancer cells.

Herceptin failure is a major clinical problem in breast cancer. A subset of breast cancer patients with high HER-2/neu levels eventually experience metastatic disease progression when treated with Herceptin as a single agent. Mechanistic details of development of this aggressive disease are not clea...

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Autores principales:	Aamir Ahmad, Shadan Ali, Alia Ahmed, Azfur S Ali, Avraham Raz, Wael A Sakr, K M Wahidur Rahman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/132db317f8b44411888892d7b099a6a9
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spelling	oai:doaj.org-article:132db317f8b44411888892d7b099a6a92021-11-18T08:00:32Z3, 3'-Diindolylmethane enhances the effectiveness of herceptin against HER-2/neu-expressing breast cancer cells.1932-620310.1371/journal.pone.0054657https://doaj.org/article/132db317f8b44411888892d7b099a6a92013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23372748/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Herceptin failure is a major clinical problem in breast cancer. A subset of breast cancer patients with high HER-2/neu levels eventually experience metastatic disease progression when treated with Herceptin as a single agent. Mechanistic details of development of this aggressive disease are not clear. Therefore, there is a dire need to better understand the mechanisms by which drug resistance develops and to design new combined treatments that benefit patients with aggressive breast cancer and have minimal toxicity. We hypothesized that 3, 3'-diindolylmethane (DIM), a non-toxic agent can be combined with Herceptin to treat breast cancers with high levels of HER-2/neu. Here, we evaluated the effects of Herceptin alone and in combination with DIM on cell viability, apoptosis and clonogenic assays in SKBR3 (HER-2/neu-expressing) and MDA-MB-468 (HER-2/neu negative) breast cancer cells. We found that DIM could enhance the effectiveness of Herceptin by significantly reducing cell viability, which was associated with apoptosis-induction and significant inhibition of colony formation, compared with single agent treatment. These results were consistent with the down-regulation of Akt and NF-kB p65. Mechanistic investigations revealed a significant upregulation of miR-200 and reduction of FoxM1 expression in DIM and Herceptin-treated breast cancer cells. We, therefore, transfected cells with pre-miR-200 or silenced FoxM1 in these cells for understanding the molecular mechanism involved. These results provide experimental evidence, for the first time, that DIM plus Herceptin therapy could be translated to the clinic as a therapeutic modality to improve treatment outcome of patients with breast cancer, particularly for the patients whose tumors express high levels of HER-2/neu.Aamir AhmadShadan AliAlia AhmedAzfur S AliAvraham RazWael A SakrK M Wahidur RahmanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e54657 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Aamir Ahmad Shadan Ali Alia Ahmed Azfur S Ali Avraham Raz Wael A Sakr K M Wahidur Rahman 3, 3'-Diindolylmethane enhances the effectiveness of herceptin against HER-2/neu-expressing breast cancer cells.
description	Herceptin failure is a major clinical problem in breast cancer. A subset of breast cancer patients with high HER-2/neu levels eventually experience metastatic disease progression when treated with Herceptin as a single agent. Mechanistic details of development of this aggressive disease are not clear. Therefore, there is a dire need to better understand the mechanisms by which drug resistance develops and to design new combined treatments that benefit patients with aggressive breast cancer and have minimal toxicity. We hypothesized that 3, 3'-diindolylmethane (DIM), a non-toxic agent can be combined with Herceptin to treat breast cancers with high levels of HER-2/neu. Here, we evaluated the effects of Herceptin alone and in combination with DIM on cell viability, apoptosis and clonogenic assays in SKBR3 (HER-2/neu-expressing) and MDA-MB-468 (HER-2/neu negative) breast cancer cells. We found that DIM could enhance the effectiveness of Herceptin by significantly reducing cell viability, which was associated with apoptosis-induction and significant inhibition of colony formation, compared with single agent treatment. These results were consistent with the down-regulation of Akt and NF-kB p65. Mechanistic investigations revealed a significant upregulation of miR-200 and reduction of FoxM1 expression in DIM and Herceptin-treated breast cancer cells. We, therefore, transfected cells with pre-miR-200 or silenced FoxM1 in these cells for understanding the molecular mechanism involved. These results provide experimental evidence, for the first time, that DIM plus Herceptin therapy could be translated to the clinic as a therapeutic modality to improve treatment outcome of patients with breast cancer, particularly for the patients whose tumors express high levels of HER-2/neu.
format	article
author	Aamir Ahmad Shadan Ali Alia Ahmed Azfur S Ali Avraham Raz Wael A Sakr K M Wahidur Rahman
author_facet	Aamir Ahmad Shadan Ali Alia Ahmed Azfur S Ali Avraham Raz Wael A Sakr K M Wahidur Rahman
author_sort	Aamir Ahmad
title	3, 3'-Diindolylmethane enhances the effectiveness of herceptin against HER-2/neu-expressing breast cancer cells.
title_short	3, 3'-Diindolylmethane enhances the effectiveness of herceptin against HER-2/neu-expressing breast cancer cells.
title_full	3, 3'-Diindolylmethane enhances the effectiveness of herceptin against HER-2/neu-expressing breast cancer cells.
title_fullStr	3, 3'-Diindolylmethane enhances the effectiveness of herceptin against HER-2/neu-expressing breast cancer cells.
title_full_unstemmed	3, 3'-Diindolylmethane enhances the effectiveness of herceptin against HER-2/neu-expressing breast cancer cells.
title_sort	3, 3'-diindolylmethane enhances the effectiveness of herceptin against her-2/neu-expressing breast cancer cells.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/132db317f8b44411888892d7b099a6a9
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3, 3'-Diindolylmethane enhances the effectiveness of herceptin against HER-2/neu-expressing breast cancer cells.

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