Ketone Bodies Induce Unique Inhibition of Tumor Cell Proliferation and Enhance the Efficacy of Anti-Cancer Agents
The ketone bodies, sodium and lithium salts of acetoacetate (AcAc) and sodium 3-hydroxybutyrate (3-HB; commonly called beta-hydroxybutyrate) have been found to inhibit the proliferation of cancer cells. Previous studies have suggested that lithium itself may be an inhibiting agent but may be additiv...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/9/2515 |
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| author | Anna I. Miller David Diaz Bo Lin Patryk K. Krzesaj Sarah Ustoyev Alfred Shim Eugene J. Fine Ehsan Sarafraz-Yazdi Matthew R. Pincus Richard D. Feinman |
| author_facet | Anna I. Miller David Diaz Bo Lin Patryk K. Krzesaj Sarah Ustoyev Alfred Shim Eugene J. Fine Ehsan Sarafraz-Yazdi Matthew R. Pincus Richard D. Feinman |
| author_sort | Anna I. Miller |
| collection | DOAJ |
| description | The ketone bodies, sodium and lithium salts of acetoacetate (AcAc) and sodium 3-hydroxybutyrate (3-HB; commonly called beta-hydroxybutyrate) have been found to inhibit the proliferation of cancer cells. Previous studies have suggested that lithium itself may be an inhibiting agent but may be additive or synergistic with the effect of AcAc. We previously found that sodium acetoacetate (NaAcAc) inhibits the growth of human colon cancer cell line SW480. We report here similar results for several other cancer cell lines including ovarian, cervical and breast cancers. We found that NaAcAc does not kill cancer cells but rather blocks their proliferation. Similar inhibition of growth was seen in the effect of lithium ion alone (as LiCl). The effect of LiAcAc appears to be due to the combined effects of acetoacetate and the lithium ion. The ketone bodies, when given together with chemotherapeutic agents, rapamycin, methotrexate and the new peptide anti-cancer agent, PNC-27, substantially lowers their IC<sub>50</sub> values for cancer cell, killing suggesting that ketone bodies and ketogenic diets may be powerful adjunct agents in treating human cancers. |
| first_indexed | 2024-03-10T23:00:37Z |
| format | Article |
| id | doaj.art-b379fc706f9745df8ae1d84fe6abb45d |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T23:00:37Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-b379fc706f9745df8ae1d84fe6abb45d2023-11-19T09:42:25ZengMDPI AGBiomedicines2227-90592023-09-01119251510.3390/biomedicines11092515Ketone Bodies Induce Unique Inhibition of Tumor Cell Proliferation and Enhance the Efficacy of Anti-Cancer AgentsAnna I. Miller0David Diaz1Bo Lin2Patryk K. Krzesaj3Sarah Ustoyev4Alfred Shim5Eugene J. Fine6Ehsan Sarafraz-Yazdi7Matthew R. Pincus8Richard D. Feinman9Department of Cell Biology, SUNY Downstate Health Sciences University, 450 Clarkson Avenue, Brooklyn, NY 11203, USADepartment of Cell Biology, SUNY Downstate Health Sciences University, 450 Clarkson Avenue, Brooklyn, NY 11203, USADepartment of Pathology, AdventHealth, 301 Memorial Medical Pkwy, Daytona Beach, FL 32117, USADepartment of Cell Biology, SUNY Downstate Health Sciences University, 450 Clarkson Avenue, Brooklyn, NY 11203, USADepartment of Cell Biology, SUNY Downstate Health Sciences University, 450 Clarkson Avenue, Brooklyn, NY 11203, USADepartment of Cell Biology, SUNY Downstate Health Sciences University, 450 Clarkson Avenue, Brooklyn, NY 11203, USADepartment of Radiology (Nuclear Medicine), Albert Einstein College of Medicine, New York, NY 10461, USANomoCan Pharmaceuticals LLC, New York Blood Center, 310 East 67th Street, New York, NY 10065, USADepartment of Pathology, SUNY Downstate Health Sciences University, 450 Clarkson Avenue, Brooklyn, NY 11203, USADepartment of Cell Biology, SUNY Downstate Health Sciences University, 450 Clarkson Avenue, Brooklyn, NY 11203, USAThe ketone bodies, sodium and lithium salts of acetoacetate (AcAc) and sodium 3-hydroxybutyrate (3-HB; commonly called beta-hydroxybutyrate) have been found to inhibit the proliferation of cancer cells. Previous studies have suggested that lithium itself may be an inhibiting agent but may be additive or synergistic with the effect of AcAc. We previously found that sodium acetoacetate (NaAcAc) inhibits the growth of human colon cancer cell line SW480. We report here similar results for several other cancer cell lines including ovarian, cervical and breast cancers. We found that NaAcAc does not kill cancer cells but rather blocks their proliferation. Similar inhibition of growth was seen in the effect of lithium ion alone (as LiCl). The effect of LiAcAc appears to be due to the combined effects of acetoacetate and the lithium ion. The ketone bodies, when given together with chemotherapeutic agents, rapamycin, methotrexate and the new peptide anti-cancer agent, PNC-27, substantially lowers their IC<sub>50</sub> values for cancer cell, killing suggesting that ketone bodies and ketogenic diets may be powerful adjunct agents in treating human cancers.https://www.mdpi.com/2227-9059/11/9/2515ketone bodieschemotherapeutic agentscancer cell viabilityIC<sub>50</sub> values |
| spellingShingle | Anna I. Miller David Diaz Bo Lin Patryk K. Krzesaj Sarah Ustoyev Alfred Shim Eugene J. Fine Ehsan Sarafraz-Yazdi Matthew R. Pincus Richard D. Feinman Ketone Bodies Induce Unique Inhibition of Tumor Cell Proliferation and Enhance the Efficacy of Anti-Cancer Agents Biomedicines ketone bodies chemotherapeutic agents cancer cell viability IC<sub>50</sub> values |
| title | Ketone Bodies Induce Unique Inhibition of Tumor Cell Proliferation and Enhance the Efficacy of Anti-Cancer Agents |
| title_full | Ketone Bodies Induce Unique Inhibition of Tumor Cell Proliferation and Enhance the Efficacy of Anti-Cancer Agents |
| title_fullStr | Ketone Bodies Induce Unique Inhibition of Tumor Cell Proliferation and Enhance the Efficacy of Anti-Cancer Agents |
| title_full_unstemmed | Ketone Bodies Induce Unique Inhibition of Tumor Cell Proliferation and Enhance the Efficacy of Anti-Cancer Agents |
| title_short | Ketone Bodies Induce Unique Inhibition of Tumor Cell Proliferation and Enhance the Efficacy of Anti-Cancer Agents |
| title_sort | ketone bodies induce unique inhibition of tumor cell proliferation and enhance the efficacy of anti cancer agents |
| topic | ketone bodies chemotherapeutic agents cancer cell viability IC<sub>50</sub> values |
| url | https://www.mdpi.com/2227-9059/11/9/2515 |
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