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

ABSTRACT: 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 1? [IL-1?], interleukin-4 [IL-4], nuclear factor ?B subunit 1 [NF?B1], and prostaglandin-endoperoxide synthase 2 [PTGS2]), tumor nitric oxide level, and serum IL-1?, 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.

SUBMITTER: Mohamad NE

PROVIDER: S-EPMC6876173 | biostudies-literature | 2019 Jan-Dec

REPOSITORIES: biostudies-literature

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

Mohamad Nurul Elyani NE Abu Nadiah N Yeap Swee Keong SK Alitheen Noorjahan Banu NB

Integrative cancer therapies 20190101

<b>Background:</b> This study aimed to evaluate the antitumor enhancing effect of bromelain consumption on 4T1-challenged mice treated with cisplatin. <b>Methods:</b> 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 ...[more]

PMID: 31752555

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Project description:Cancer nano-therapy has been progressing rapidly with the introduction of many novel drug delivery systems. The previous study has reported on the in vitro cytotoxicity of citral-loaded nanostructured lipid carrier (NLC-Citral) on MDA-MB-231 cells and some preliminary in vivo antitumor effects on 4T1 breast cancer cells challenged mice. However, the in vivo apoptosis induction and anti-metastatic effects of NLC-Citral have yet to be reported. In this study, the in vitro cytotoxic, anti-migration, and anti-invasion effects of NLC-Citral were tested on 4T1 breast cancer cells. In addition, the in vivo antitumor effects of oral delivery of NLC-Citral was also evaluated on BALB/c mice induced with 4T1 cells. In vitro cytotoxicity results showed that NLC-Citral and citral gave similar IC50 values on 4T1 cells. However, wound healing, migration, and invasion assays reflected better in vitro anti-metastasis potential for NLC-Citral than citral alone. Results from the in vivo study indicated that both NLC-Citral and citral have anti-tumor and anti-metastasis effects, whereby the NLC-Citral showed better efficacy than citral in all experiments. Also, the delay of tumor progression was through the suppression of the c-myc gene expression and induction of apoptosis in the tumor. In addition, the inhibition of metastasis of 4T1 cells to lung and bone marrow by the NLC-Citral and citral treatments was correlated with the downregulation of metastasis-related genes expression including MMP-9, ICAM, iNOS, and NF-kB and the angiogenesis-related proteins including G-CSF alpha, Eotaxin, bFGF, VEGF, IL-1alpha, and M-CSF in the tumor. Moreover, NLC-Citral showed greater downregulation of MMP-9, iNOS, ICAM, Eotaxin, bFGF, VEGF, and M-CSF than citral treatment in the 4T1-challenged mice, which may contribute to the better anti-metastatic effect of the encapsulated citral. This study suggests that NLC is a potential and effective delivery system for citral to target triple-negative breast cancer.

Dataset Information

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

Publications

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

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