Free Fatty Acids from Cow Urine DMSO Fraction Induce Cell Death in Breast Cancer Cells without Affecting Normal GMSCs

Biomedicines · 7 authors, 5 centres

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TL;DR

A DMSO-fractionated cow urine extract enriched with free fatty acids was tested on breast cancer cell lines and normal cells.

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567 CHARS

CUDF was prepared from cow urine, fractionated in DMSO, and filtered for cell-based assays. The extract was applied to MCF-7 (caspase 3-deficient) and ZR-75-1 (caspase 3-active) breast cancer cell lines, both with wild-type p53. The Discussion reports that CUDF treatment led to substantial loss of viability and apoptotic cell death in both cell lines, with more pronounced apoptotic cell death in ZR-75-1 cells. Intracellular profiling of CUDF-treated MCF-7 cells identified FFAs including tetracosanedioic acid, 13-docosenoic acid (erucic acid), and nervonic acid.

STUDY TYPE

other

SPECIALTY

oncology

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AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10046047

Free Fatty Acids from Cow Urine DMSO Fraction Induce Cell Death in Breast Cancer Cells without Affecting Normal GMSCs

Biomedicines

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ABSTRACT

Abstract Objective: The objective of this study was to explore the biological relevance of free fatty acids derived from cow urine DMSO fraction (CUDF) by employing in vitro and in silico approaches. Background: Metabolic heterogeneity at the intra- and intercellular levels contributes to the metabolic plasticity of cancer cells during drug-induced response. Free fatty acid (FFA) availability at intra- and intercellular levels is related to tumor heterogeneity at interpatient and xeno-heterogeneity levels. Methods: We collected fresh urine from healthy cows and subjected it to fractionation in DMSO using drying, vortexing, and centrifugation. Finally, the sterile filtrate of cow urine DMSO fraction (CUDF) was evaluated for antiproliferative and proapoptotic effects in MCF-7 and ZR-75-1 breast cancer cells using routine cell-based assays. Intracellular metabolites were studied with the help of a novel in-house vertical tube gel electrophoresis (VTGE) method to reveal the nature of CUDF components in MCF-7 cells. Identified intracellular FFAs were studied for their molecular interactions with targeted receptor histone deacetylase (HDAC) using molecular docking and molecular dynamics (MD) simulations. Results: CUDF showed a significant reduction in cell viability and cell death in MCF-7 and ZR-75-1 breast cancer cells. Interestingly, FFAs tetracosanedioic acid, 13Z-docosenoic acid (erucic acid), nervonic acid, 3-hydroxy-tetradecanoic acid, and 3-hydroxcapric acid were found inside the treated MCF-7 cancer cells. These FFAs, including tetracosanedioic acid, indicated a specific affinity to HDAC at their inhibitory sites, similar to trichostatin A, a known inhibitor. Conclusions: This study reports on FFAs derived from CUDF as potential antiproliferative and pro-cell death agents against breast cancer cells. MD simulations hinted at tetracosanedioic acid and other FFAs as inhibitors of HDAC that could explain the observed effects of FFAs in cancer cells. Keywords: metabolites, cancer, apoptosis, cytotoxicity, free fatty acids, molecular dynamics, simulations, epigenetic enzyme

CITATION EXPORT

Ajay Kumar Raj, Vidhi Upadhyay, Kiran Bharat Lokhande et al.. Free Fatty Acids from Cow Urine DMSO Fraction Induce Cell Death in Breast Cancer Cells without Affecting Normal GMSCs. Biomedicines. (2023). https://doi.org/10.3390/biomedicines11030889

AUTHORS

7 · 5 CENTRES

Ajay Kumar Raj, Vidhi Upadhyay, Kiran Bharat Lokhande, K Venkateswara Swamy, Ramesh Ramchandra Bhonde, Sachin C Sarode, Nilesh Kumar Sharma

1Cancer and Translational Research Lab, Dr. D. Y. Patil Biotechnology & Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune 411033, Maharashtra, India
2Bioinformatics Research Laboratory, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune 411033, Maharashtra, India
3MIT-School of Bioengineering Sciences & Research, MIT-Art, Design and Technology University, Pune 412201, Maharashtra, India
4Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College and Hospital, Dr. Y. Patil Vidyapeeth, Pimpri, Pune 411018, Maharashtra, India
5Department of Oral Pathology and Microbiology, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune 411018, Maharashtra, India