The MDA-MB-231 Breast Cancer Cell Secretomes Modify Metabolomes of Pseudomonas aeruginosa Breast Microbiome
Abstract
1. Introduction
2. Results
2.1. Breast Cancer-Conditioned Media Suppress the Growth Rate of Pseudomonas aeruginosa
2.2. Breast Cancer-Conditioned Media Alter P. aeruginosa Cell Morphology
2.3. Metabolites Induced by MDA-MB-231-Conditioned Media
2.4. Breast Cancer-Conditioned Media Disrupts P. aeruginosa Metabolomics Profile
3. Discussion
4. Methodology
4.1. Breast Cancer-Conditioned Media Preparation
4.2. Bacterial Culture and Growth Assessment by Optical Density
4.3. Morphology Analysis by Scanning Electron Microscopy (SEM)
4.4. Preparation of Metabolite Extracts from the Cells and Supernatants (Secretomes)
4.5. Metabolomics Analysis
LC-MS Metabolomics
4.6. Data and Statistical Analysis
4.7. Metabolites Identification
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Ma, J.; Gnanasekar, A.; Lee, A.; Li, W.T.; Haas, M.; Wang-Rodriguez, J.; Chang, E.Y.; Rajasekaran, M.; Ongkeko, W.M. Influence of intratumor microbiome on clinical outcome and immune processes in prostate cancer. Cancers 2020, 12, 2524. [Google Scholar] [CrossRef] [PubMed]
- Suliman, B.A. The impact of consanguinity on women’s attitudes toward molecular testing of breast cancer in Saudi Arabia. Breast Cancer Manag. 2021, 10, BMT57. [Google Scholar] [CrossRef]
- Sun, Y.-S.; Zhao, Z.; Yang, Z.-N.; Xu, F.; Lu, H.-J.; Zhu, Z.-Y.; Shi, W.; Jiang, J.; Yao, P.-P.; Zhu, H.-P. Risk factors and preventions of breast cancer. Int. J. Biol. Sci. 2017, 13, 1387. [Google Scholar] [CrossRef] [PubMed]
- Mikó, E.; Kovács, T.; Sebő, É.; Tóth, J.; Csonka, T.; Ujlaki, G.; Sipos, A.; Szabó, J.; Méhes, G.; Bai, P. Microbiome—Microbial Metabolome—Cancer Cell Interactions in Breast Cancer—Familiar, but Unexplored. Cells 2019, 8, 293. [Google Scholar] [CrossRef]
- Al-Ansari, M.M.; Almalki, R.H.; Dahabiyeh, L.A.; Abdel Rahman, A.M. Metabolomics-microbiome crosstalk in the breast cancer microenvironment. Metabolites 2021, 11, 758. [Google Scholar] [CrossRef]
- Chan, A.A.; Bashir, M.; Rivas, M.N.; Duvall, K.; Sieling, P.A.; Pieber, T.R.; Vaishampayan, P.A.; Love, S.M.; Lee, D.J. Characterization of the microbiome of nipple aspirate fluid of breast cancer survivors. Sci. Rep. 2016, 6, 28061. [Google Scholar] [CrossRef]
- Klann, E.; Williamson, J.M.; Tagliamonte, M.S.; Ukhanova, M.; Asirvatham, J.R.; Chim, H.; Yaghjyan, L.; Mai, V. Microbiota composition in bilateral healthy breast tissue and breast tumors. Cancer Causes Control. 2020, 31, 1027–1038. [Google Scholar] [CrossRef]
- Lai, T.C.; Chou, H.C.; Chen, Y.W.; Lee, T.R.; Chan, H.T.; Shen, H.H.; Lee, W.T.; Lin, S.T.; Lu, Y.C.; Wu, C.L.; et al. Secretomic and proteomic analysis of potential breast cancer markers by two-dimensional differential gel electrophoresis. J. Proteome Res. 2010, 9, 1302–1322. [Google Scholar] [CrossRef]
- Meng, S.; Chen, B.; Yang, J.; Wang, J.; Zhu, D.; Meng, Q.; Zhang, L. Study of microbiomes in aseptically collected samples of human breast tissue using needle biopsy and the potential role of in situ tissue microbiomes for promoting malignancy. Front. Oncol. 2018, 8, 318. [Google Scholar] [CrossRef]
- Plottel, C.S.; Blaser, M.J. Microbiome and malignancy. Cell Host Microbe 2011, 10, 324–335. [Google Scholar] [CrossRef]
- Marcinowska, R.; Trygg, J.; Wolf-Watz, H.; Mortiz, T.; Surowiec, I. Optimization of a sample preparation method for the metabolomic analysis of clinically relevant bacteria. J. Microbiol. Methods 2011, 87, 24–31. [Google Scholar] [CrossRef] [PubMed]
- Brauer, H.A.; Makowski, L.; Hoadley, K.A.; Casbas-Hernandez, P.; Lang, L.J.; Romàn-Pèrez, E.; D’Arcy, M.; Freemerman, A.J.; Perou, C.M.; Troester, M.A. Impact of tumor microenvironment and epithelial phenotypes on metabolism in breast cancer. Clin. Cancer Res. 2013, 19, 571–585. [Google Scholar] [CrossRef]
- Abdelaziz, A.A.; Kamer, A.M.A.; Al-Monofy, K.B.; Al-Madboly, L.A. A purified and lyophilized Pseudomonas aeruginosa derived pyocyanin induces promising apoptotic and necrotic activities against MCF-7 human breast adenocarcinoma. Microb. Cell Factories 2022, 21, 262. [Google Scholar] [CrossRef]
- Wang, N.; Sun, T.; Xu, J. Tumor-related Microbiome in the Breast Microenvironment and Breast Cancer. J. Cancer 2021, 12, 4841–4848. [Google Scholar] [CrossRef]
- Ghasemi-Dehkordi, P.; Doosti, A.; Jami, M.S. The functions of azurin of Pseudomonas aeruginosa and human mammaglobin-A on proapoptotic and cell cycle regulatory genes expression in the MCF-7 breast cancer cell line. Saudi J. Biol. Sci. 2020, 27, 2308–2317. [Google Scholar] [CrossRef]
- Al-Ansari, M.M.; Al-Saif, M.; Arafah, M.; Eldali, A.M.; Tulbah, A.; Al-Tweigeri, T.; Semlali, A.; Khabar, K.S.; Aboussekhra, A. Clinical and functional significance of tumor/stromal ATR expression in breast cancer patients. Breast Cancer Res. 2020, 22, 49. [Google Scholar] [CrossRef]
- Rabiei, P.; Mohabatkar, H.; Behbahani, M. Studying the effects of several heat-inactivated bacteria on colon and breast cancer cells. Mol. Biol. Res. Commun. 2019, 8, 91–98. [Google Scholar] [CrossRef]
- Mielko, K.A.; Jabłoński, S.J.; Łukaszewicz, M.; Młynarz, P. Comparison of bacteria disintegration methods and their influence on data analysis in metabolomics. Sci. Rep. 2021, 11, 20859. [Google Scholar] [CrossRef]
- Arnone, A.A.; Cook, K.L. Gut and Breast Microbiota as Endocrine Regulators of Hormone Receptor-positive Breast Cancer Risk and Therapy Response. Endocrinology 2023, 164, bqac177. [Google Scholar] [CrossRef]
- AlMalki, R.H.; Sebaa, R.; Al-Ansari, M.M.; Al-Alwan, M.; Alwehaibi, M.A.; Rahman, A.M.A. E. coli Secretome Metabolically Modulates MDA-MB-231 Breast Cancer Cells’ Energy Metabolism. Int. J. Mol. Sci. 2023, 24, 4219. [Google Scholar] [CrossRef]
- Jobin, C. Precision medicine using microbiota. Science 2018, 359, 32–34. [Google Scholar] [CrossRef] [PubMed]
- Urbaniak, C.; Gloor, G.B.; Brackstone, M.; Scott, L.; Tangney, M.; Reid, G. The Microbiota of Breast Tissue and Its Association with Breast Cancer. Appl. Environ. Microbiol. 2016, 82, 5039–5048. [Google Scholar] [CrossRef] [PubMed]
- Punj, V.; Bhattacharyya, S.; Saint-Dic, D.; Vasu, C.; Cunningham, E.A.; Graves, J.; Yamada, T.; Constantinou, A.I.; Christov, K.; White, B.; et al. Bacterial cupredoxin azurin as an inducer of apoptosis and regression in human breast cancer. Oncogene 2004, 23, 2367–2378. [Google Scholar] [CrossRef]
- Chiba, A.; Bawaneh, A.; Velazquez, C.; Clear, K.Y.J.; Wilson, A.S.; Howard-McNatt, M.; Levine, E.A.; Levi-Polyachenko, N.; Yates-Alston, S.A.; Diggle, S.P.; et al. Neoadjuvant Chemotherapy Shifts Breast Tumor Microbiota Populations to Regulate Drug Responsiveness and the Development of Metastasis. Mol. Cancer Res. 2020, 18, 130–139. [Google Scholar] [CrossRef]
- Qin, G.; Shao, X.; Liu, X.; Xu, J.; Wang, X.; Wang, W.; Gao, L.; Liang, Y.; Xie, L.; Su, D.; et al. A signaling molecule from intratumor bacteria promotes trastuzumab resistance in breast cancer cells. Proc. Natl. Acad. Sci. USA 2025, 122, e2421710122. [Google Scholar] [CrossRef]
- Taware, R.; More, T.H.; Bagadi, M.; Taunk, K.; Mane, A.; Rapole, S. Lipidomics investigations into the tissue phospholipidomic landscape of invasive ductal carcinoma of the breast. RSC Adv. 2020, 11, 397–407. [Google Scholar] [CrossRef]
- Winter, J.N.; Fox, T.E.; Kester, M.; Jefferson, L.S.; Kimball, S.R. Phosphatidic acid mediates activation of mTORC1 through the ERK signaling pathway. Am. J. Physiol. Cell Physiol. 2010, 299. [Google Scholar] [CrossRef]
- Chagovets, V.; Starodubtseva, N.; Tokareva, A.; Novoselova, A.; Patysheva, M.; Larionova, I.; Prostakishina, E.; Rakina, M.; Kazakova, A.; Topolnitskiy, E.; et al. Specific changes in amino acid profiles in monocytes of patients with breast, lung, colorectal and ovarian cancers. Front. Immunol. 2023, 14, 1332043. [Google Scholar] [CrossRef]
- Ahmadpour, S.T.; Mahéo, K.; Servais, S.; Brisson, L.; Dumas, J.F. Cardiolipin, the mitochondrial signature lipid: Implication in cancer. Int. J. Mol. Sci. 2020, 21, 8031. [Google Scholar] [CrossRef]
- Dong, C.; Wu, J.; Chen, Y.; Nie, J.; Chen, C. Activation of PI3K/AKT/mTOR Pathway Causes Drug Resistance in Breast Cancer. Front. Pharmacol. 2021, 12, 628690. [Google Scholar] [CrossRef]
- Icard, P.; Coquerel, A.; Wu, Z.; Gligorov, J.; Fuks, D.; Fournel, L.; Lincet, H.; Simula, L. Understanding the central role of citrate in the metabolism of cancer cells and tumors: An update. Int. J. Mol. Sci. 2021, 22, 6587. [Google Scholar] [CrossRef] [PubMed]
- Ying, T.H.; Chen, C.W.; Hsiao, Y.P.; Hung, S.J.; Chung, J.G.; Yang, J.H. Citric acid induces cell-cycle arrest and apoptosis of human immortalized keratinocyte cell line (HaCaT) via caspase- and mitochondrial-dependent signaling pathways. Anticancer. Res. 2013, 33, 4411–4420. [Google Scholar]
- Munteanu, C.; Mârza, S.M.; Papuc, I. The immunomodulatory effects of vitamins in cancer. Front. Immunol. 2024, 15, 1464329. [Google Scholar] [CrossRef]
- Yong, J.; Cai, S.; Zeng, Z. Targeting NAD+ metabolism: Dual roles in cancer treatment. Front. Immunol. 2023, 14, 1269896. [Google Scholar] [CrossRef]
- Tosi, G.; Paoli, A.; Zuccolotto, G.; Turco, E.; Simonato, M.; Tosoni, D.; Tucci, F.; Lugato, P.; Giomo, M.; Elvassore, N.; et al. Cancer cell stiffening via CoQ10 and UBIAD1 regulates ECM signaling and ferroptosis in breast cancer. Nat. Commun. 2024, 15, 8214. [Google Scholar] [CrossRef]
- Arnold, J.M.; Gu, F.; Ambati, C.R.; Rasaily, U.; Ramirez-Pena, E.; Joseph, R.; Manikkam, M.; San Martin, R.; Charles, C.; Pan, Y.; et al. UDP-glucose 6-dehydrogenase regulates hyaluronic acid production and promotes breast cancer progression. Oncogene 2020, 39, 3089–3101. [Google Scholar] [CrossRef]
- Adapa, S.R.; Hunter, G.A.; Amin, N.E.; Marinescu, C.; Borsky, A.; Sagatys, E.M.; Sebti, S.M.; Reuther, G.W.; Ferreira, G.C.; Jiang, R.H. Heme overdrive rewires pan-cancer cell metabolism. bioRxiv 2022. [Google Scholar] [CrossRef]
- Akter, Z.; Salamat, N.; Ali, M.Y.; Zhang, L. The promise of targeting heme and mitochondrial respiration in normalizing tumor microenvironment and potentiating immunotherapy. Front. Oncol. 2023, 12, 1072739. [Google Scholar] [CrossRef]
- Soda, K. The mechanisms by which polyamines accelerate tumor spread. J. Exp. Clin. Cancer Res. 2011, 30, 95. [Google Scholar] [CrossRef]
- Martínez-Montiel, N.; Rosas-Murrieta, N.H.; Martínez-Montiel, M.; Gaspariano-Cholula, M.P.; Martínez-Contreras, R.D. Microbial and Natural Metabolites That Inhibit Splicing: A Powerful Alternative for Cancer Treatment. BioMed Res. Int. 2016, 2016, 3681094. [Google Scholar] [CrossRef]
- McCarthy, N. Therapeutics: Promoting a mixed message. Nat. Rev. Cancer 2007, 7, 640. [Google Scholar] [CrossRef]
- Braud, A.; Hannauer, M.; Mislin, G.L.A.; Schalk, I.J. The Pseudomonas aeruginosa pyochelin-iron uptake pathway and its metal specificity. J. Bacteriol. 2009, 191, 3517–3525. [Google Scholar] [CrossRef] [PubMed]
- Swayambhu, G.; Bruno, M.; Gulick, A.M.; Pfeifer, B.A. Siderophore natural products as pharmaceutical agents. Curr. Opin. Biotechnol. 2021, 69, 242–251. [Google Scholar] [CrossRef] [PubMed]
- Guo, Y.; Han, Z.; Min, H.; Chen, Z.; Sun, T.; Wang, L.; Shi, W.; Cheng, P. A Europium-Organic Framework Sensing Material for 2-Aminoacetophenone, a Bacterial Biomarker in Water. Inorg. Chem. 2021, 60, 9192–9198. [Google Scholar] [CrossRef]
- Jenal, U. Cyclic di-guanosine-monophosphate comes of age: A novel secondary messenger involved in modulating cell surface structures in bacteria? Curr. Opin. Microbiol. 2004, 7, 185–191. [Google Scholar] [CrossRef]
- Bhutia, Y.D.; Ganapathy, V. Glutamine transporters in mammalian cells and their functions in physiology and cancer. Biochim. Et Biophys. Acta Mol. Cell Res. 2016, 1863, 2531–2539. [Google Scholar] [CrossRef]
- Lamont, I.L.; Beare, P.A.; Ochsner, U.; Vasil, A.I.; Vasil, M.L. Siderophore-mediated signaling regulates virulence factor production in Pseudomonas aeruginosa. Proc. Natl. Acad. Sci. USA 2002, 99, 7072–7077. [Google Scholar] [CrossRef]
- Mould, D.L.; Botelho, N.J.; Hogan, D.A. Intraspecies signaling between common variants of pseudomonas aeruginosa increases production of quorum-sensing-controlled virulence factors. mBio 2020, 11, 10–1128. [Google Scholar] [CrossRef]
- Chiarugi, A.; Dölle, C.; Felici, R.; Ziegler, M. The NAD metabolome - A key determinant of cancer cell biology. Nat. Rev. Cancer 2012, 12, 741–752. [Google Scholar] [CrossRef]
- Chen, C.; Yan, W.; Tao, M.; Fu, Y. NAD+ Metabolism and Immune Regulation: New Approaches to Inflammatory Bowel Disease Therapies. Antioxidants 2023, 12, 1230. [Google Scholar] [CrossRef]
- St Germain, M.; Iraji, R.; Bakovic, M. Phosphatidylethanolamine homeostasis under conditions of impaired CDP-ethanolamine pathway or phosphatidylserine decarboxylation. Front. Nutr. 2023, 9, 1094273. [Google Scholar] [CrossRef] [PubMed]
- Picas, L.; Montero, M.T.; Morros, A.; Vázquez-Ibar, J.L.; Hernández-Borrell, J. Evidence of phosphatidylethanolamine and phosphatidylglycerol presence at the annular region of lactose permease of Escherichia coli. Biochim. Et Biophys. Acta-Biomembr. 2010, 1798, 291–296. [Google Scholar] [CrossRef] [PubMed]
- Prado, L.G.; Camara, N.O.S.; Barbosa, A.S. Cell lipid biology in infections: An overview. Front. Cell. Infect. Microbiol. 2023, 13, 1148383. [Google Scholar] [CrossRef]
- La Rosa, R.; Johansen, H.K.; Molin, S. Adapting to the airways: Metabolic requirements of Pseudomonas aeruginosa during the infection of cystic fibrosis patients. Metabolites 2019, 9, 234. [Google Scholar] [CrossRef]
- Berg, G.M.; Jørgensen, N.O.G. Purine and pyrimidine metabolism by estuarine bacteria. Aquat. Microb. Ecol. 2006, 42, 215–226. [Google Scholar] [CrossRef]
- Das, D.; Hervé, M.; Elsliger, M.A.; Kadam, R.U.; Grant, J.C.; Chiu, H.J.; Knuth, M.W.; Klock, H.E.; Miller, M.D.; Godzik, A.; et al. Structure and function of a novel LD-Carboxypeptidase a involved in peptidoglycan recycling. J. Bacteriol. 2013, 195, 5555–5566. [Google Scholar] [CrossRef]
- Schmidberger, J.W.; Schnell, R.; Schneider, G. Structural characterization of substrate and inhibitor binding to farnesyl pyrophosphate synthase from Pseudomonas aeruginosa. Acta Crystallogr. Sect. D Biol. Crystallogr. 2015, 71, 721–731. [Google Scholar] [CrossRef]
- Dwivedy, A.; Ashraf, A.; Jha, B.; Kumar, D.; Agarwal, N.; Biswal, B.K. De novo histidine biosynthesis protects Mycobacterium tuberculosis from host IFN-γ mediated histidine starvation. Commun. Biol. 2021, 4, 410. [Google Scholar] [CrossRef]
- Javid-Majd, F.; Yang, D.; Ioerger, T.R.; Sacchettini, J.C. The 1.25 Å resolution structure of phosphoribosyl-ATP pyrophosphohydrolase from Mycobacterium tuberculosis. Acta Crystallogr. Sect. D Biol. Crystallogr. 2008, 64, 627–635. [Google Scholar] [CrossRef]
- Newton, A.C.; Bootman, M.D.; Scott, J. Second messengers. Cold Spring Harb. Perspect. Biol. 2016, 8, 1–14. [Google Scholar] [CrossRef]
- Nguyen, A.H.; Hood, K.S.; Mileykovskaya, E.; Miller, W.R.; Tran, T.T. Bacterial cell membranes and their role in daptomycin resistance: A review. Front. Mol. Biosci. 2022, 9, 1035574. [Google Scholar] [CrossRef] [PubMed]
- Tang, S.; Hou, Y.; Zhang, H.; Tu, G.; Yang, L.; Sun, Y.; Lang, L.; Tang, X.; Du, Y.e.; Zhou, M.; et al. Oxidized ATM promotes abnormal proliferation of breast CAFs through maintaining intracellular redox homeostasis and activating the PI3K-AKT, MEK-ERK, and Wnt-β-catenin signaling pathways. Cell Cycle 2015, 14, 1908–1924. [Google Scholar] [CrossRef]
- Song, Y.H.; Warncke, C.; Choi, S.J.; Choi, S.; Chiou, A.E.; Ling, L.; Liu, H.Y.; Daniel, S.; Antonyak, M.A.; Cerione, R.A.; et al. Breast cancer-derived extracellular vesicles stimulate myofibroblast differentiation and pro-angiogenic behavior of adipose stem cells. Matrix Biol. 2017, 60–61, 190–205. [Google Scholar] [CrossRef]
- Ziuzina, D.; Patil, S.; Cullen, P.J.; Boehm, D.; Bourke, P. Dielectric barrier discharge atmospheric cold plasma for inactivation of Pseudomonas aeruginosa biofilms. Plasma Med. 2014, 4, 137–152. [Google Scholar] [CrossRef]
- Mohd Kamal, K.; Mahamad Maifiah, M.H.; Abdul Rahim, N.; Hashim, Y.Z.H.Y.; Abdullah Sani, M.S.; Azizan, K.A. Bacterial Metabolomics: Sample Preparation Methods. Biochem. Res. Int. 2022, 2022, 9186536. [Google Scholar] [CrossRef]
- Alotaibi, A.Z.; AlMalki, R.H.; Al Mogren, M.; Sebaa, R.; Alanazi, M.; Jacob, M.; Alodaib, A.; Alfares, A.; Abdel Rahman, A.M. Exploratory Untargeted Metabolomics of Dried Blood Spot Samples from Newborns with Maple Syrup Urine Disease. Int. J. Mol. Sci. 2024, 25, 5720. [Google Scholar] [CrossRef]
- Pang, Z.; Chong, J.; Zhou, G.; De Lima Morais, D.A.; Chang, L.; Barrette, M.; Gauthier, C.; Jacques, P.É.; Li, S.; Xia, J. MetaboAnalyst 5.0: Narrowing the gap between raw spectra and functional insights. Nucleic Acids Res. 2021, 49, W388–W396. [Google Scholar] [CrossRef]
- Worley, B.; Powers, R. Multivariate Analysis in Metabolomics. Curr. Metabolomics 2013, 1, 92–107. [Google Scholar] [CrossRef]
- Gu, X.; Al Dubayee, M.; Alshahrani, A.; Masood, A.; Benabdelkamel, H.; Zahra, M.; Li, L.; Abdel Rahman, A.M.; Aljada, A. Distinctive Metabolomics Patterns Associated With Insulin Resistance and Type 2 Diabetes Mellitus. Front. Mol. Biosci. 2020, 7, 609806. [Google Scholar] [CrossRef]
Compound Name | p Value [3] vs. [0] | FC * [3] vs. [0] | Log FC [3] vs. [0] | Regulation [3] vs. [0] | Effect on Breast Cancer |
---|---|---|---|---|---|
PC(22:6(5Z,7Z,10Z,13Z,16Z,19Z)-OH(4)/14:1(9Z)) | <0.0005 | 16 | −4 | down | Affects cell proliferation through membrane and lipid signaling [26]. |
PA(2:0/20:5(7Z,9Z,11E,13E,17Z)-3OH(5,6,15)) | <0.0005 | 16 | −4 | down | Enhances cell survival and proliferation via mTOR activation [27]. |
Citrulline | <0.0005 | 4.9266753 | 2.3006144 | up | Involved in NO production, promoting angiogenesis, immune suppression, and inflammation [28]. |
PGP(18:3(9Z,12Z,15Z)/ 20:5(7Z,9Z,11E,13E,17Z)-3OH(5,6,15)) | <0.0005 | 16 | −4 | down | Precursor of cardiolipin, linked to cancer progression [29]. |
PIP2(16:0/16:0) | <0.0005 | 16 | −4 | down | PI3K activation supports cell growth and resistance to apoptosis [30]. |
Citric acid | <0.0005 | 16 | −4 | down | Involved in TCA cycle; can induce cell cycle arrest and promote apoptosis [31,32]. |
Riboflavin | <0.0005 | 16 | −4 | down | Mixed effects; can inhibit or promote cell proliferation and invasion at high doses [33]. |
NAD | <0.0005 | 4.3397436 | 2.1176097 | up | Elevated NAD⁺ levels support the metabolic demands of proliferating cancer cells [34]. |
Ubiquinol-4 | <0.0005 | 2.0339475 | 1.0242825 | up | Enhances mitochondrial efficiency, supporting cell metabolism and growth [35]. |
Compound Name | p Value [6] vs. [0] | FC [6] vs. [0] | Log FC [6] vs. [0] | Regulation [6] vs. [0] | Effect on Breast Cancer |
---|---|---|---|---|---|
Uridine diphosphate glucuronic acid | <0.0001 | 14.774896 | −3.885076 | down | Promotes tumor growth and metastasis via increased hyaluronic acid production [36]. |
Citrulline | <0.0001 | 16 | −4 | down | Influences NO production, angiogenesis, immune suppression, and chronic inflammation in cancer [28]. |
Heme O | <0.0001 | 4.720601 | 2.2389705 | up | Enhances mitochondrial respiration and supports the metabolic needs of cancer cells [37,38]. |
Decarboxy-SAM | <0.0001 | 15.084385 | −3.914984 | down | Regulates polyamine biosynthesis, promoting tumor growth, invasion, and metastasis [39]. |
Metabolite Name | p-Value | Regulation | Role |
---|---|---|---|
FR901464 cytotoxic | 0.002690988 | Up | Anti-proliferation effect on cancer cells due to its ability to regulate the splicing process [40,41]. |
Pyochelin I siderophore | 0.030434728 | Up | Inhibits cancer cells’ proliferation or leads to cancer cell death [42,43]. |
2-aminoacetophenone | <0.0001 | Up | Able to encourage persistent cells formation within host cells by altering the metabolic pathways in immune cells to their advantage [44]. |
Guanosine monophosphate | 0.018803272 | Up | Affects cell–cell/cell–surface interactions in biofilm formation [45]. |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
AlDawsari, M.; Al-Ansari, M.M.; AlMalki, R.H.; Rahman, A.M.A.; Al-Alwan, M. The MDA-MB-231 Breast Cancer Cell Secretomes Modify Metabolomes of Pseudomonas aeruginosa Breast Microbiome. Int. J. Mol. Sci. 2025, 26, 5003. https://doi.org/10.3390/ijms26115003
AlDawsari M, Al-Ansari MM, AlMalki RH, Rahman AMA, Al-Alwan M. The MDA-MB-231 Breast Cancer Cell Secretomes Modify Metabolomes of Pseudomonas aeruginosa Breast Microbiome. International Journal of Molecular Sciences. 2025; 26(11):5003. https://doi.org/10.3390/ijms26115003
Chicago/Turabian StyleAlDawsari, Majdoleen, Mysoon M. Al-Ansari, Reem H. AlMalki, Anas M. Abdel Rahman, and Monther Al-Alwan. 2025. "The MDA-MB-231 Breast Cancer Cell Secretomes Modify Metabolomes of Pseudomonas aeruginosa Breast Microbiome" International Journal of Molecular Sciences 26, no. 11: 5003. https://doi.org/10.3390/ijms26115003
APA StyleAlDawsari, M., Al-Ansari, M. M., AlMalki, R. H., Rahman, A. M. A., & Al-Alwan, M. (2025). The MDA-MB-231 Breast Cancer Cell Secretomes Modify Metabolomes of Pseudomonas aeruginosa Breast Microbiome. International Journal of Molecular Sciences, 26(11), 5003. https://doi.org/10.3390/ijms26115003