Potential Utility of Synthetic D-Lactate Polymers in Skin Cancer
Increased breakdown of glucose through glycolysis in both aerobic and anaerobic conditions is a hallmark feature of mammalian cancer and leads to increased production of L-lactate. The high-level lactate present within the tumor microenvironment is reused as a crucial biofuel to support rapid cancer...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-09-01
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| Series: | JID Innovations |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667026721000448 |
| _version_ | 1818690317321240576 |
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| author | Anushka Dikshit Junqi Lu Amy E. Ford Simone Degan Yingai J. Jin Huiying Sun Amanda Nichols April K.S. Salama Georgia Beasley David Gooden Jennifer Y. Zhang |
| author_facet | Anushka Dikshit Junqi Lu Amy E. Ford Simone Degan Yingai J. Jin Huiying Sun Amanda Nichols April K.S. Salama Georgia Beasley David Gooden Jennifer Y. Zhang |
| author_sort | Anushka Dikshit |
| collection | DOAJ |
| description | Increased breakdown of glucose through glycolysis in both aerobic and anaerobic conditions is a hallmark feature of mammalian cancer and leads to increased production of L-lactate. The high-level lactate present within the tumor microenvironment is reused as a crucial biofuel to support rapid cancer cell proliferation, survival, and immune evasion. Inhibitors that target the glycolysis process are being developed for cancer therapy. In this study, we report an approach of using synthetic D-lactate dimers to inhibit melanoma and squamous cell carcinoma cell proliferation and survival. We also provide in vivo evidence that intratumoral injection of D-lactate dimers induced an innate immune response and inhibited subcutaneous melanoma xenograft growth in immunodeficient mice. Our findings support a potential utility of D-lactate dimers in skin cancer treatment and therefore warrant further mechanistic studies. |
| first_indexed | 2024-12-17T12:24:05Z |
| format | Article |
| id | doaj.art-52d95ec5c2a74a83941f919612cebe33 |
| institution | Directory Open Access Journal |
| issn | 2667-0267 |
| language | English |
| last_indexed | 2024-12-17T12:24:05Z |
| publishDate | 2021-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JID Innovations |
| spelling | doaj.art-52d95ec5c2a74a83941f919612cebe332022-12-21T21:48:50ZengElsevierJID Innovations2667-02672021-09-0113100043Potential Utility of Synthetic D-Lactate Polymers in Skin CancerAnushka Dikshit0Junqi Lu1Amy E. Ford2Simone Degan3Yingai J. Jin4Huiying Sun5Amanda Nichols6April K.S. Salama7Georgia Beasley8David Gooden9Jennifer Y. Zhang10Department of Dermatology, Duke University Medical Center, Durham, North Carolina, USADepartment of Dermatology, Duke University Medical Center, Durham, North Carolina, USADepartment of Dermatology, Duke University Medical Center, Durham, North Carolina, USADepartment of Dermatology, Duke University Medical Center, Durham, North Carolina, USADepartment of Dermatology, Duke University Medical Center, Durham, North Carolina, USADepartment of Dermatology, Duke University Medical Center, Durham, North Carolina, USADepartment of Pediatrics, Duke University Medical Center, Durham, North Carolina, USADepartment of Medicine, Duke University Medical Center, Durham, North Carolina, USADepartment of Surgery, Duke University Medical Center, Durham, North Carolina, USADepartment of Chemistry, Duke University, Durham, North Carolina, USADepartment of Dermatology, Duke University Medical Center, Durham, North Carolina, USA; Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA; Correspondence: Jennifer Y. Zhang, Department of Dermatology, Duke University Medical Center, PO Box 103052, Durham, North Carolina 27710, USA.Increased breakdown of glucose through glycolysis in both aerobic and anaerobic conditions is a hallmark feature of mammalian cancer and leads to increased production of L-lactate. The high-level lactate present within the tumor microenvironment is reused as a crucial biofuel to support rapid cancer cell proliferation, survival, and immune evasion. Inhibitors that target the glycolysis process are being developed for cancer therapy. In this study, we report an approach of using synthetic D-lactate dimers to inhibit melanoma and squamous cell carcinoma cell proliferation and survival. We also provide in vivo evidence that intratumoral injection of D-lactate dimers induced an innate immune response and inhibited subcutaneous melanoma xenograft growth in immunodeficient mice. Our findings support a potential utility of D-lactate dimers in skin cancer treatment and therefore warrant further mechanistic studies.http://www.sciencedirect.com/science/article/pii/S2667026721000448 |
| spellingShingle | Anushka Dikshit Junqi Lu Amy E. Ford Simone Degan Yingai J. Jin Huiying Sun Amanda Nichols April K.S. Salama Georgia Beasley David Gooden Jennifer Y. Zhang Potential Utility of Synthetic D-Lactate Polymers in Skin Cancer JID Innovations |
| title | Potential Utility of Synthetic D-Lactate Polymers in Skin Cancer |
| title_full | Potential Utility of Synthetic D-Lactate Polymers in Skin Cancer |
| title_fullStr | Potential Utility of Synthetic D-Lactate Polymers in Skin Cancer |
| title_full_unstemmed | Potential Utility of Synthetic D-Lactate Polymers in Skin Cancer |
| title_short | Potential Utility of Synthetic D-Lactate Polymers in Skin Cancer |
| title_sort | potential utility of synthetic d lactate polymers in skin cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2667026721000448 |
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