Zapotin mitigates breast cancer progression by targeting PKCε mediated glycolytic pathway regulation
Abstract Background The breast cancer recurrence and chemoresistance has increased over the years. A novel PKC, PKCε, may promote chemoresistance by causing hypoxia and cancer metabolic rewiring. A natural flavonoid, Zapotin, in colon cancer cells may modulate PKCε expression. Therefore, this study...
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BMC
2025-04-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-025-14202-z |
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| author | Khushbukhat Khan Maryam Anwar Yasmin Badshah Naeem Mahmood Ashraf Arslan Hamid Janeen H. Trembley Maria Shabbir Tayyaba Afsar Fohad Mabood Husain Dilawar Khan Suhail Razak |
| author_facet | Khushbukhat Khan Maryam Anwar Yasmin Badshah Naeem Mahmood Ashraf Arslan Hamid Janeen H. Trembley Maria Shabbir Tayyaba Afsar Fohad Mabood Husain Dilawar Khan Suhail Razak |
| author_sort | Khushbukhat Khan |
| collection | DOAJ |
| description | Abstract Background The breast cancer recurrence and chemoresistance has increased over the years. A novel PKC, PKCε, may promote chemoresistance by causing hypoxia and cancer metabolic rewiring. A natural flavonoid, Zapotin, in colon cancer cells may modulate PKCε expression. Therefore, this study aimed to explore Zapotin impact on PKCε expression and the metabolic profile of breast cancer cells. Methods Pharmacophore analysis of Zapotin was performed and molecular dynamics (MD) simulations were employed to study PKCε and Zapotin interaction stability. The effect of Zapotin treatment on PKCε expression and various aspects of cancer cell viability and metabolism was studied in MCF-7 and MDA-MB-231 breast cancer cell lines using real-time PCR, growth and death assays, and Gas Chromatography-Mass Spectrometry. Results In silico analyses revealed good solubility and absorption of Zapotin with lower toxicity. Zapotin showed cancer cell-specific cytotoxicity (P < 0.0001). It’s treatment also reduced breast cancer cell viability, colony formation, and migratory potential by targeting PKCε and associated HIF-1ɑ and VEGF signaling (P < 0.01). Zapotin also impacted PKCε-mediated metabolic signaling by targeting glycolytic pathways. Conclusion This study demonstrated the role of PKCε mediated HIF-1ɑ, VEGF, and glycolytic pathways in promoting breast carcinogenicity and demonstrated Zapotin as a potential treatment option for different types of breast tumors. |
| format | Article |
| id | doaj-art-b7add137b3a140df968b0f6dbe596b5e |
| institution | DOAJ |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj-art-b7add137b3a140df968b0f6dbe596b5e2025-08-20T02:55:38ZengBMCBMC Cancer1471-24072025-04-0125111910.1186/s12885-025-14202-zZapotin mitigates breast cancer progression by targeting PKCε mediated glycolytic pathway regulationKhushbukhat Khan0Maryam Anwar1Yasmin Badshah2Naeem Mahmood Ashraf3Arslan Hamid4Janeen H. Trembley5Maria Shabbir6Tayyaba Afsar7Fohad Mabood Husain8Dilawar Khan9Suhail Razak10Department of Biomedicine, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST)Department of Biomedicine, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST)Department of Biomedicine, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST)School of Biochemistry & Biotechnology, University of the PunjabLIMES Institute (AG-Netea), University of BonnDepartment of Laboratory Medicine and Pathology, University of MinnesotaDepartment of Biomedicine, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST)Department of Community Health Sciences, College of Applied Medical Sciences, King Saud UniversityDepartment of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud UniversityDepartment of Biomedicine, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST)Department of Community Health Sciences, College of Applied Medical Sciences, King Saud UniversityAbstract Background The breast cancer recurrence and chemoresistance has increased over the years. A novel PKC, PKCε, may promote chemoresistance by causing hypoxia and cancer metabolic rewiring. A natural flavonoid, Zapotin, in colon cancer cells may modulate PKCε expression. Therefore, this study aimed to explore Zapotin impact on PKCε expression and the metabolic profile of breast cancer cells. Methods Pharmacophore analysis of Zapotin was performed and molecular dynamics (MD) simulations were employed to study PKCε and Zapotin interaction stability. The effect of Zapotin treatment on PKCε expression and various aspects of cancer cell viability and metabolism was studied in MCF-7 and MDA-MB-231 breast cancer cell lines using real-time PCR, growth and death assays, and Gas Chromatography-Mass Spectrometry. Results In silico analyses revealed good solubility and absorption of Zapotin with lower toxicity. Zapotin showed cancer cell-specific cytotoxicity (P < 0.0001). It’s treatment also reduced breast cancer cell viability, colony formation, and migratory potential by targeting PKCε and associated HIF-1ɑ and VEGF signaling (P < 0.01). Zapotin also impacted PKCε-mediated metabolic signaling by targeting glycolytic pathways. Conclusion This study demonstrated the role of PKCε mediated HIF-1ɑ, VEGF, and glycolytic pathways in promoting breast carcinogenicity and demonstrated Zapotin as a potential treatment option for different types of breast tumors.https://doi.org/10.1186/s12885-025-14202-zProtein kinase C epsilonZapotinMD simulationsBreast cancerMetabolic rewiring |
| spellingShingle | Khushbukhat Khan Maryam Anwar Yasmin Badshah Naeem Mahmood Ashraf Arslan Hamid Janeen H. Trembley Maria Shabbir Tayyaba Afsar Fohad Mabood Husain Dilawar Khan Suhail Razak Zapotin mitigates breast cancer progression by targeting PKCε mediated glycolytic pathway regulation BMC Cancer Protein kinase C epsilon Zapotin MD simulations Breast cancer Metabolic rewiring |
| title | Zapotin mitigates breast cancer progression by targeting PKCε mediated glycolytic pathway regulation |
| title_full | Zapotin mitigates breast cancer progression by targeting PKCε mediated glycolytic pathway regulation |
| title_fullStr | Zapotin mitigates breast cancer progression by targeting PKCε mediated glycolytic pathway regulation |
| title_full_unstemmed | Zapotin mitigates breast cancer progression by targeting PKCε mediated glycolytic pathway regulation |
| title_short | Zapotin mitigates breast cancer progression by targeting PKCε mediated glycolytic pathway regulation |
| title_sort | zapotin mitigates breast cancer progression by targeting pkcε mediated glycolytic pathway regulation |
| topic | Protein kinase C epsilon Zapotin MD simulations Breast cancer Metabolic rewiring |
| url | https://doi.org/10.1186/s12885-025-14202-z |
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