Role of Testosterone Levels on the Combinatorial Effect of Extract and Enzalutamide on Androgen Dependent LNCaP Cells and in Patient Derived Cells

Co-therapy with herbal extracts along with current clinical drugs is being increasingly recognized as a useful complementary treatment for cancer. The anti-cancer property of the phyto-derivative acetyl-11 keto β boswellic acid (AKBA) has been studied in many cancers, including prostate cancer. Howe...

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Autores principales:	Prathesha Pillai MSc, Ginil Kumar Pooleri MCh, Shantikumar V. Nair PhD
Formato:	article
Lenguaje:	EN
Publicado:	SAGE Publishing 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/77d41f12135d426d8804469e47e58b99
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spelling	oai:doaj.org-article:77d41f12135d426d8804469e47e58b992021-12-04T06:03:19ZRole of Testosterone Levels on the Combinatorial Effect of Extract and Enzalutamide on Androgen Dependent LNCaP Cells and in Patient Derived Cells1534-73541552-695X10.1177/1534735421996824https://doaj.org/article/77d41f12135d426d8804469e47e58b992021-02-01T00:00:00Zhttps://doi.org/10.1177/1534735421996824https://doaj.org/toc/1534-7354https://doaj.org/toc/1552-695XCo-therapy with herbal extracts along with current clinical drugs is being increasingly recognized as a useful complementary treatment for cancer. The anti-cancer property of the phyto-derivative acetyl-11 keto β boswellic acid (AKBA) has been studied in many cancers, including prostate cancer. However, the whole extract of the gum resin Boswellia serrata (BS) and anti-androgen enzalutamide has not been explored in prostate cancer to date. We hypothesized that the BS extract containing 30% (AKBA) with enzalutamide acted synergistically in the early phase of cancer, especially in LNCaP cells, by inhibiting androgen receptor (AR) and by reducing cell proliferation, and further, that the extract would be superior to the action of the active ingredient AKBA when used alone or in combination with enzalutamide. To test our hypothesis, we treated LNCaP cells with BS extract or AKBA and enzalutamide both individually and in combination to analyze cell viability under different levels of dihydrotestosterone (DHT). The inhibition of androgen receptor (AR) followed by the expression of prostate-specific antigen (PSA) and the efflux mechanism of the cells were analyzed to determine the effect of the combination on the cellular mechanism. Cells derived from prostate cancer patients were also tested with the combination. Only 6 µM enzalutamide along with BS in the range of 4.1 µg/ml to 16.4 µg/ml gave the best synergistic results with nearly 50% cell killing even though standard enzalutamide doses were as high as 48 µM. Cell killing was most effective at intermediate DHT concentrations of approximately 1 nM, which corresponds to normal physiological serum levels of DHT. The Pgp expression level and the androgen receptor expression levels were reduced under the combination treatment; the former helping to minimize drug efflux and the latter by reducing the sensitivity to hormonal changes. Furthermore, the combination reduced the PSA level secreted by the cells. In contrast, AKBA could not achieve the needed synergism for adequate cell killing at equivalent concentrations. The combination of enzalutamide and BS extract containing 30% AKBA because of their synergistic interaction is an attractive therapeutic option for treating early stage (hormone-dependent) prostate cancer and is superior to the use of AKBA alone.Prathesha Pillai MScGinil Kumar Pooleri MChShantikumar V. Nair PhDSAGE PublishingarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENIntegrative Cancer Therapies, Vol 20 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Prathesha Pillai MSc Ginil Kumar Pooleri MCh Shantikumar V. Nair PhD Role of Testosterone Levels on the Combinatorial Effect of Extract and Enzalutamide on Androgen Dependent LNCaP Cells and in Patient Derived Cells
description	Co-therapy with herbal extracts along with current clinical drugs is being increasingly recognized as a useful complementary treatment for cancer. The anti-cancer property of the phyto-derivative acetyl-11 keto β boswellic acid (AKBA) has been studied in many cancers, including prostate cancer. However, the whole extract of the gum resin Boswellia serrata (BS) and anti-androgen enzalutamide has not been explored in prostate cancer to date. We hypothesized that the BS extract containing 30% (AKBA) with enzalutamide acted synergistically in the early phase of cancer, especially in LNCaP cells, by inhibiting androgen receptor (AR) and by reducing cell proliferation, and further, that the extract would be superior to the action of the active ingredient AKBA when used alone or in combination with enzalutamide. To test our hypothesis, we treated LNCaP cells with BS extract or AKBA and enzalutamide both individually and in combination to analyze cell viability under different levels of dihydrotestosterone (DHT). The inhibition of androgen receptor (AR) followed by the expression of prostate-specific antigen (PSA) and the efflux mechanism of the cells were analyzed to determine the effect of the combination on the cellular mechanism. Cells derived from prostate cancer patients were also tested with the combination. Only 6 µM enzalutamide along with BS in the range of 4.1 µg/ml to 16.4 µg/ml gave the best synergistic results with nearly 50% cell killing even though standard enzalutamide doses were as high as 48 µM. Cell killing was most effective at intermediate DHT concentrations of approximately 1 nM, which corresponds to normal physiological serum levels of DHT. The Pgp expression level and the androgen receptor expression levels were reduced under the combination treatment; the former helping to minimize drug efflux and the latter by reducing the sensitivity to hormonal changes. Furthermore, the combination reduced the PSA level secreted by the cells. In contrast, AKBA could not achieve the needed synergism for adequate cell killing at equivalent concentrations. The combination of enzalutamide and BS extract containing 30% AKBA because of their synergistic interaction is an attractive therapeutic option for treating early stage (hormone-dependent) prostate cancer and is superior to the use of AKBA alone.
format	article
author	Prathesha Pillai MSc Ginil Kumar Pooleri MCh Shantikumar V. Nair PhD
author_facet	Prathesha Pillai MSc Ginil Kumar Pooleri MCh Shantikumar V. Nair PhD
author_sort	Prathesha Pillai MSc
title	Role of Testosterone Levels on the Combinatorial Effect of Extract and Enzalutamide on Androgen Dependent LNCaP Cells and in Patient Derived Cells
title_short	Role of Testosterone Levels on the Combinatorial Effect of Extract and Enzalutamide on Androgen Dependent LNCaP Cells and in Patient Derived Cells
title_full	Role of Testosterone Levels on the Combinatorial Effect of Extract and Enzalutamide on Androgen Dependent LNCaP Cells and in Patient Derived Cells
title_fullStr	Role of Testosterone Levels on the Combinatorial Effect of Extract and Enzalutamide on Androgen Dependent LNCaP Cells and in Patient Derived Cells
title_full_unstemmed	Role of Testosterone Levels on the Combinatorial Effect of Extract and Enzalutamide on Androgen Dependent LNCaP Cells and in Patient Derived Cells
title_sort	role of testosterone levels on the combinatorial effect of extract and enzalutamide on androgen dependent lncap cells and in patient derived cells
publisher	SAGE Publishing
publishDate	2021
url	https://doaj.org/article/77d41f12135d426d8804469e47e58b99
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Role of Testosterone Levels on the Combinatorial Effect of Extract and Enzalutamide on Androgen Dependent LNCaP Cells and in Patient Derived Cells

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