Research Article
Year 2023,
Volume: 14 Issue: 2, 97 - 102, 17.03.2023
Abstract
References
- Newman JC, Verdin E. β-Hydroxybutyrate. Annu Rev Nutr. 2017 Aug 21;37:51–76.
- Veech RL. The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. Prostaglandins, Leukotrienes and Essential Fatty Acids. 2004 Mar 1;70(3):309–19.
- Stafstrom CE, Rho JM. The ketogenic diet as a treatment paradigm for diverse neurological disorders. Front Pharmacol. 2012 Apr 1;3:59.
- Weber DD, Aminzadeh-Gohari S, Tulipan J, Catalano L, Feichtinger RG, Kofler B. Ketogenic diet in the treatment of cancer – Where do we stand? Molecular Metabolism. 2020 Mar 1;33:102–21.
- Strowd RE, Cervenka MC, Henry BJ, Kossoff EH, Hartman AL, Blakeley JO. Glycemic modulation in neuro-oncology: experience and future directions using a modified Atkins diet for high-grade brain tumors. Neurooncol Pract. 2015 Sep;2(3):127–36.
- Champ CE, Palmer JD, Volek JS, Werner-Wasik M, Andrews DW, Evans JJ, et al. Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme. J Neurooncol. 2014 Mar;117(1):125–31.
- Seyfried TN, Marsh J, Shelton LM, Huysentruyt LC, Mukherjee P. Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer? Epilepsy Research. 2012 Jul 1;100(3):310–26.
- Zhao H, Jin H, Xian J, Zhang Z, Shi J, Bai X. Effect of Ketogenic Diets on Body Composition and Metabolic Parameters of Cancer Patients: A Systematic Review and Meta-Analysis. Nutrients. 2022 Oct 8;14(19):4192.
- Maurer GD, Brucker DP, Bähr O, Harter PN, Hattingen E, Walenta S, et al. Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy. BMC Cancer. 2011 Jul 26;11:315.
- Rieger J, Bähr O, Maurer GD, Hattingen E, Franz K, Brucker D, et al. ERGO: a pilot study of ketogenic diet in recurrent glioblastoma. Int J Oncol. 2014 Jun;44(6):1843–52.
- Seyfried TN, Sanderson TM, El-Abbadi MM, McGowan R, Mukherjee P. Role of glucose and ketone bodies in the metabolic control of experimental brain cancer. Br J Cancer. 2003 Oct 6;89(7):1375–82.
- Zahra A, Fath MA, Opat E, Mapuskar KA, Bhatia SK, Ma DC, et al. Consuming a Ketogenic Diet while Receiving Radiation and Chemotherapy for Locally Advanced Lung Cancer and Pancreatic Cancer: The University of Iowa Experience of Two Phase 1 Clinical Trials. Radiation Research. 2017 Apr 24;187(6):743–54.
- Allen BG, Bhatia SK, Buatti JM, Brandt KE, Lindholm KE, Button AM, et al. Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts. Clin Cancer Res. 2013 Jul 15;19(14):3905–13.
- Byrne FL, Hargett SR, Lahiri S, Roy RJ, Berr SS, Caldwell SH, et al. Serial MRI Imaging Reveals Minimal Impact of Ketogenic Diet on Established Liver Tumor Growth. Cancers (Basel). 2018 Sep 5;10(9):312.
- Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA A Cancer J Clinicians. 2022 Jan;72(1):7–33.
- Lin BQ, Zeng ZY, Yang SS, Zhuang CW. Dietary restriction suppresses tumor growth, reduces angiogenesis, and improves tumor microenvironment in human non-small-cell lung cancer xenografts. Lung Cancer. 2013 Feb;79(2):111–7.
- Iyikesici MS. Feasibility study of metabolically supported chemotherapy with weekly carboplatin/paclitaxel combined with ketogenic diet, hyperthermia and hyperbaric oxygen therapy in metastatic non-small cell lung cancer. Int J Hyperthermia. 2019 Apr 1;36(1):446–55.
- Vichai V, Kirtikara K. Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat Protoc. 2006 Aug;1(3):1112–6.
- Liang CC, Park AY, Guan JL. In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc. 2007 Feb 1;2(2):329–33.
- Woolf EC, Syed N, Scheck AC. Tumor Metabolism, the Ketogenic Diet and β-Hydroxybutyrate: Novel Approaches to Adjuvant Brain Tumor Therapy. Front Mol Neurosci. 2016 Nov 16;9:122.
- Mikami D, Kobayashi M, Uwada J, Yazawa T, Kamiyama K, Nishimori K, et al. β-Hydroxybutyrate enhances the cytotoxic effect of cisplatin via the inhibition of HDAC/survivin axis in human hepatocellular carcinoma cells. Journal of Pharmacological Sciences. 2020 Jan 1;142(1):1–8.
- Shukla SK, Chaika NV, Singh PK. Abstract 3557: Beta-hydroxybutyrate inhibits oncogenic signaling and cellular motility in pancreatic cancer cells. Cancer Research. 2018 Jul 1;78(13_Supplement):3557.
- Shang S, Wang L, Zhang Y, Lu H, Lu X. The Beta-Hydroxybutyrate Suppresses the Migration of Glioma Cells by Inhibition of NLRP3 Inflammasome. Cell Mol Neurobiol. 2018 Nov 1;38(8):1479–89.
- Yao A, Li Z, Lyu J, Yu L, Wei S, Xue L, et al. On the nutritional and therapeutic effects of ketone body d-β-hydroxybutyrate. Appl Microbiol Biotechnol. 2021;105(16–17):6229–43.
- Bartmann C, Janaki Raman SR, Flöter J, Schulze A, Bahlke K, Willingstorfer J, et al. Beta-hydroxybutyrate (3-OHB) can influence the energetic phenotype of breast cancer cells, but does not impact their proliferation and the response to chemotherapy or radiation. Cancer & Metabolism. 2018 Jun 11;6(1):8.
- De Feyter HM, Behar KL, Rao JU, Madden-Hennessey K, Ip KL, Hyder F, et al. A ketogenic diet increases transport and oxidation of ketone bodies in RG2 and 9L gliomas without affecting tumor growth. Neuro-Oncology. 2016 Aug 1;18(8):1079–87.
Year 2023,
Volume: 14 Issue: 2, 97 - 102, 17.03.2023
Abstract
Background/Purpose: The metabolic shift from catabolism of carbohydrates to lipids results in production of ketone bodies leading to a state called ketosis. Ketosis via ketone supplement or ketogenic diet has been proposed as a non-toxic therapeutic option for a broad range of malignancies. Although the clinical impact of ketogenic diet is well-documented, the effect of ketone bodies on cancer cell biology is not clear for some cancers including non-small-cell lung cancer (NSCLC). In this study, we aimed to demonstrate the effects of the most prominent ketone body, β-hydroxybutyrate, on a NSCLC cell line, A549.
Methods: A549 cell line was utilized as the in vitro model in this study. The effects of different β-hydroxybutyrate concentrations on cell viability were measured via sulforhodamine-B (SRB) viability assay. Long term effects of ketosis were evaluated via colony formation assay. Finally, the effect of β-hydroxybutyrate on cell migration was determined via scratch assay.
Results: Our results suggest that introduction of β-hydroxybutyrate in physiologically relevant concentrations into the cell culture media does not influence cell viability, clonogenicity or migration.
Conclusion: β-hydroxybutyrate has been previously demonstrated to induce, inhibit or does not influence the viability of different cell lines but there is no report regarding its effects on NSCLC cells. Here we report that physiologically relevant concentrations of β-hydroxybutyrate have no effect on viability, clonogenicity and migration of A549 cells.
Keywords
References
- Newman JC, Verdin E. β-Hydroxybutyrate. Annu Rev Nutr. 2017 Aug 21;37:51–76.
- Veech RL. The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. Prostaglandins, Leukotrienes and Essential Fatty Acids. 2004 Mar 1;70(3):309–19.
- Stafstrom CE, Rho JM. The ketogenic diet as a treatment paradigm for diverse neurological disorders. Front Pharmacol. 2012 Apr 1;3:59.
- Weber DD, Aminzadeh-Gohari S, Tulipan J, Catalano L, Feichtinger RG, Kofler B. Ketogenic diet in the treatment of cancer – Where do we stand? Molecular Metabolism. 2020 Mar 1;33:102–21.
- Strowd RE, Cervenka MC, Henry BJ, Kossoff EH, Hartman AL, Blakeley JO. Glycemic modulation in neuro-oncology: experience and future directions using a modified Atkins diet for high-grade brain tumors. Neurooncol Pract. 2015 Sep;2(3):127–36.
- Champ CE, Palmer JD, Volek JS, Werner-Wasik M, Andrews DW, Evans JJ, et al. Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme. J Neurooncol. 2014 Mar;117(1):125–31.
- Seyfried TN, Marsh J, Shelton LM, Huysentruyt LC, Mukherjee P. Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer? Epilepsy Research. 2012 Jul 1;100(3):310–26.
- Zhao H, Jin H, Xian J, Zhang Z, Shi J, Bai X. Effect of Ketogenic Diets on Body Composition and Metabolic Parameters of Cancer Patients: A Systematic Review and Meta-Analysis. Nutrients. 2022 Oct 8;14(19):4192.
- Maurer GD, Brucker DP, Bähr O, Harter PN, Hattingen E, Walenta S, et al. Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy. BMC Cancer. 2011 Jul 26;11:315.
- Rieger J, Bähr O, Maurer GD, Hattingen E, Franz K, Brucker D, et al. ERGO: a pilot study of ketogenic diet in recurrent glioblastoma. Int J Oncol. 2014 Jun;44(6):1843–52.
- Seyfried TN, Sanderson TM, El-Abbadi MM, McGowan R, Mukherjee P. Role of glucose and ketone bodies in the metabolic control of experimental brain cancer. Br J Cancer. 2003 Oct 6;89(7):1375–82.
- Zahra A, Fath MA, Opat E, Mapuskar KA, Bhatia SK, Ma DC, et al. Consuming a Ketogenic Diet while Receiving Radiation and Chemotherapy for Locally Advanced Lung Cancer and Pancreatic Cancer: The University of Iowa Experience of Two Phase 1 Clinical Trials. Radiation Research. 2017 Apr 24;187(6):743–54.
- Allen BG, Bhatia SK, Buatti JM, Brandt KE, Lindholm KE, Button AM, et al. Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts. Clin Cancer Res. 2013 Jul 15;19(14):3905–13.
- Byrne FL, Hargett SR, Lahiri S, Roy RJ, Berr SS, Caldwell SH, et al. Serial MRI Imaging Reveals Minimal Impact of Ketogenic Diet on Established Liver Tumor Growth. Cancers (Basel). 2018 Sep 5;10(9):312.
- Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA A Cancer J Clinicians. 2022 Jan;72(1):7–33.
- Lin BQ, Zeng ZY, Yang SS, Zhuang CW. Dietary restriction suppresses tumor growth, reduces angiogenesis, and improves tumor microenvironment in human non-small-cell lung cancer xenografts. Lung Cancer. 2013 Feb;79(2):111–7.
- Iyikesici MS. Feasibility study of metabolically supported chemotherapy with weekly carboplatin/paclitaxel combined with ketogenic diet, hyperthermia and hyperbaric oxygen therapy in metastatic non-small cell lung cancer. Int J Hyperthermia. 2019 Apr 1;36(1):446–55.
- Vichai V, Kirtikara K. Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat Protoc. 2006 Aug;1(3):1112–6.
- Liang CC, Park AY, Guan JL. In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc. 2007 Feb 1;2(2):329–33.
- Woolf EC, Syed N, Scheck AC. Tumor Metabolism, the Ketogenic Diet and β-Hydroxybutyrate: Novel Approaches to Adjuvant Brain Tumor Therapy. Front Mol Neurosci. 2016 Nov 16;9:122.
- Mikami D, Kobayashi M, Uwada J, Yazawa T, Kamiyama K, Nishimori K, et al. β-Hydroxybutyrate enhances the cytotoxic effect of cisplatin via the inhibition of HDAC/survivin axis in human hepatocellular carcinoma cells. Journal of Pharmacological Sciences. 2020 Jan 1;142(1):1–8.
- Shukla SK, Chaika NV, Singh PK. Abstract 3557: Beta-hydroxybutyrate inhibits oncogenic signaling and cellular motility in pancreatic cancer cells. Cancer Research. 2018 Jul 1;78(13_Supplement):3557.
- Shang S, Wang L, Zhang Y, Lu H, Lu X. The Beta-Hydroxybutyrate Suppresses the Migration of Glioma Cells by Inhibition of NLRP3 Inflammasome. Cell Mol Neurobiol. 2018 Nov 1;38(8):1479–89.
- Yao A, Li Z, Lyu J, Yu L, Wei S, Xue L, et al. On the nutritional and therapeutic effects of ketone body d-β-hydroxybutyrate. Appl Microbiol Biotechnol. 2021;105(16–17):6229–43.
- Bartmann C, Janaki Raman SR, Flöter J, Schulze A, Bahlke K, Willingstorfer J, et al. Beta-hydroxybutyrate (3-OHB) can influence the energetic phenotype of breast cancer cells, but does not impact their proliferation and the response to chemotherapy or radiation. Cancer & Metabolism. 2018 Jun 11;6(1):8.
- De Feyter HM, Behar KL, Rao JU, Madden-Hennessey K, Ip KL, Hyder F, et al. A ketogenic diet increases transport and oxidation of ketone bodies in RG2 and 9L gliomas without affecting tumor growth. Neuro-Oncology. 2016 Aug 1;18(8):1079–87.
There are 26 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Biochemistry and Cell Biology (Other) |
| Journal Section | Research Article |
| Authors | |
| Publication Date | March 17, 2023 |
| Submission Date | December 19, 2022 |
| Published in Issue | Year 2023Volume: 14 Issue: 2 |
