Free Fatty Acids from Cow Urine DMSO Fraction Induce Cell Death in Breast Cancer Cells without Affecting Normal GMSCs
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 plast...
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MDPI AG
2023-03-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/3/889 |
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| author | Ajay Kumar Raj Vidhi Upadhyay Kiran Bharat Lokhande K. Venkateswara Swamy Ramesh Ramchandra Bhonde Sachin C. Sarode Nilesh Kumar Sharma |
| author_facet | Ajay Kumar Raj Vidhi Upadhyay Kiran Bharat Lokhande K. Venkateswara Swamy Ramesh Ramchandra Bhonde Sachin C. Sarode Nilesh Kumar Sharma |
| author_sort | Ajay Kumar Raj |
| collection | DOAJ |
| description | 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. |
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| language | English |
| last_indexed | 2024-03-11T06:53:46Z |
| publishDate | 2023-03-01 |
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| spelling | doaj.art-a3be7ad8db3c4392a995da333283ea7d2023-11-17T09:47:06ZengMDPI AGBiomedicines2227-90592023-03-0111388910.3390/biomedicines11030889Free Fatty Acids from Cow Urine DMSO Fraction Induce Cell Death in Breast Cancer Cells without Affecting Normal GMSCsAjay Kumar Raj0Vidhi Upadhyay1Kiran Bharat Lokhande2K. Venkateswara Swamy3Ramesh Ramchandra Bhonde4Sachin C. Sarode5Nilesh Kumar Sharma6Cancer and Translational Research Lab, Dr. D. Y. Patil Biotechnology & Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune 411033, Maharashtra, IndiaCancer and Translational Research Lab, Dr. D. Y. Patil Biotechnology & Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune 411033, Maharashtra, IndiaBioinformatics Research Laboratory, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune 411033, Maharashtra, IndiaMIT-School of Bioengineering Sciences & Research, MIT-Art, Design and Technology University, Pune 412201, Maharashtra, IndiaRegenerative Medicine Laboratory, Dr. D. Y. Patil Dental College and Hospital, Dr. Y. Patil Vidyapeeth, Pimpri, Pune 411018, Maharashtra, IndiaDepartment of Oral Pathology and Microbiology, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune 411018, Maharashtra, IndiaCancer and Translational Research Lab, Dr. D. Y. Patil Biotechnology & Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune 411033, Maharashtra, IndiaObjective: 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.https://www.mdpi.com/2227-9059/11/3/889metabolitescancerapoptosiscytotoxicityfree fatty acidsmolecular dynamics |
| spellingShingle | Ajay Kumar Raj Vidhi Upadhyay Kiran Bharat Lokhande K. Venkateswara Swamy Ramesh Ramchandra Bhonde Sachin C. Sarode Nilesh Kumar Sharma Free Fatty Acids from Cow Urine DMSO Fraction Induce Cell Death in Breast Cancer Cells without Affecting Normal GMSCs Biomedicines metabolites cancer apoptosis cytotoxicity free fatty acids molecular dynamics |
| title | Free Fatty Acids from Cow Urine DMSO Fraction Induce Cell Death in Breast Cancer Cells without Affecting Normal GMSCs |
| title_full | Free Fatty Acids from Cow Urine DMSO Fraction Induce Cell Death in Breast Cancer Cells without Affecting Normal GMSCs |
| title_fullStr | Free Fatty Acids from Cow Urine DMSO Fraction Induce Cell Death in Breast Cancer Cells without Affecting Normal GMSCs |
| title_full_unstemmed | Free Fatty Acids from Cow Urine DMSO Fraction Induce Cell Death in Breast Cancer Cells without Affecting Normal GMSCs |
| title_short | Free Fatty Acids from Cow Urine DMSO Fraction Induce Cell Death in Breast Cancer Cells without Affecting Normal GMSCs |
| title_sort | free fatty acids from cow urine dmso fraction induce cell death in breast cancer cells without affecting normal gmscs |
| topic | metabolites cancer apoptosis cytotoxicity free fatty acids molecular dynamics |
| url | https://www.mdpi.com/2227-9059/11/3/889 |
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