Bromelain Enhances the Anti-tumor Effects of Cisplatin on 4T1 Breast Tumor Model In Vivo

Background: This study aimed to evaluate the antitumor enhancing effect of bromelain consumption on 4T1-challenged mice treated with cisplatin. Methods: Mice challenged with 4T1 triple-negative breast cancer cells received water, bromelain, cisplatin, or bromelain + cisplatin treatment for 28 days....

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Main Authors: Nurul Elyani Mohamad PhD, Nadiah Abu PhD, Swee Keong Yeap PhD, Noorjahan Banu Alitheen PhD
Format: Article
Language:English
Published: SAGE Publishing 2019-10-01
Series:Integrative Cancer Therapies
Online Access:https://doi.org/10.1177/1534735419880258
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spelling doaj-f7d4d19787814ba3a9f28ba49ed0f6782020-11-25T03:41:11ZengSAGE PublishingIntegrative Cancer Therapies1552-695X2019-10-011810.1177/1534735419880258Bromelain Enhances the Anti-tumor Effects of Cisplatin on 4T1 Breast Tumor Model In VivoNurul Elyani Mohamad PhD0Nadiah Abu PhD1Swee Keong Yeap PhD2Noorjahan Banu Alitheen PhD3Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor, MalaysiaUKM Medical Molecular Biology Institute (UMBI), UKM Medical Centre, Kuala Lumpur, MalaysiaChina-ASEAN College of Marine Sciences, Xiamen University Malaysia, Sepang, Selangor, MalaysiaFaculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor, MalaysiaBackground: This study aimed to evaluate the antitumor enhancing effect of bromelain consumption on 4T1-challenged mice treated with cisplatin. Methods: Mice challenged with 4T1 triple-negative breast cancer cells received water, bromelain, cisplatin, or bromelain + cisplatin treatment for 28 days. Tumor size was measured, and lung metastasis was evaluated by clonogenic assay. Expression of tumor inflammatory genes of the harvested tumor was quantified by polymerase chain reaction array and ELISA (enzyme-linked immunosorbent assay). Results : All treatments significantly reduced the size of tumor and lung metastasis, with combination treatment showing the best effect. Also, bromelain alone and combination treatment showed downregulation of the expression of tumor inflammatory genes (Gremlin [GREM1], interleukin 1β [IL-1β], interleukin-4 [IL-4], nuclear factor κB subunit 1 [NFκB1], and prostaglandin-endoperoxide synthase 2 [PTGS2]), tumor nitric oxide level, and serum IL-1β, and IL-4 levels. On the other hand, cisplatin treatment increased the expression of selected inflammatory markers. Conclusion: This study suggests that bromelain treatment could potentiate the antitumor effect of cisplatin on triple-negative breast cancer 4T1 cells through modulating the tumor environmental inflammation.https://doi.org/10.1177/1534735419880258
collection DOAJ
language English
format Article
sources DOAJ
author Nurul Elyani Mohamad PhD
Nadiah Abu PhD
Swee Keong Yeap PhD
Noorjahan Banu Alitheen PhD
spellingShingle Nurul Elyani Mohamad PhD
Nadiah Abu PhD
Swee Keong Yeap PhD
Noorjahan Banu Alitheen PhD
Bromelain Enhances the Anti-tumor Effects of Cisplatin on 4T1 Breast Tumor Model In Vivo
Integrative Cancer Therapies
author_facet Nurul Elyani Mohamad PhD
Nadiah Abu PhD
Swee Keong Yeap PhD
Noorjahan Banu Alitheen PhD
author_sort Nurul Elyani Mohamad PhD
title Bromelain Enhances the Anti-tumor Effects of Cisplatin on 4T1 Breast Tumor Model In Vivo
title_short Bromelain Enhances the Anti-tumor Effects of Cisplatin on 4T1 Breast Tumor Model In Vivo
title_full Bromelain Enhances the Anti-tumor Effects of Cisplatin on 4T1 Breast Tumor Model In Vivo
title_fullStr Bromelain Enhances the Anti-tumor Effects of Cisplatin on 4T1 Breast Tumor Model In Vivo
title_full_unstemmed Bromelain Enhances the Anti-tumor Effects of Cisplatin on 4T1 Breast Tumor Model In Vivo
title_sort bromelain enhances the anti-tumor effects of cisplatin on 4t1 breast tumor model in vivo
publisher SAGE Publishing
series Integrative Cancer Therapies
issn 1552-695X
publishDate 2019-10-01
description Background: This study aimed to evaluate the antitumor enhancing effect of bromelain consumption on 4T1-challenged mice treated with cisplatin. Methods: Mice challenged with 4T1 triple-negative breast cancer cells received water, bromelain, cisplatin, or bromelain + cisplatin treatment for 28 days. Tumor size was measured, and lung metastasis was evaluated by clonogenic assay. Expression of tumor inflammatory genes of the harvested tumor was quantified by polymerase chain reaction array and ELISA (enzyme-linked immunosorbent assay). Results : All treatments significantly reduced the size of tumor and lung metastasis, with combination treatment showing the best effect. Also, bromelain alone and combination treatment showed downregulation of the expression of tumor inflammatory genes (Gremlin [GREM1], interleukin 1β [IL-1β], interleukin-4 [IL-4], nuclear factor κB subunit 1 [NFκB1], and prostaglandin-endoperoxide synthase 2 [PTGS2]), tumor nitric oxide level, and serum IL-1β, and IL-4 levels. On the other hand, cisplatin treatment increased the expression of selected inflammatory markers. Conclusion: This study suggests that bromelain treatment could potentiate the antitumor effect of cisplatin on triple-negative breast cancer 4T1 cells through modulating the tumor environmental inflammation.
url https://doi.org/10.1177/1534735419880258
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