Araştırma Makalesi
Yıl 2018,
Cilt: 31 Sayı: 2, 57 - 60, 05.06.2018
Öz
Amaç: Kanser hücreleri aerobik koşullar altında Warburg etkisi
olarak bilinen artmış glikolitik fenotipini sergilerler. Ayrıca,
son zamanlarda yapılan çalışmalar, kanser hücrelerinin glikoza
bağımlı olduğunu ve keton cisimlerini birincil bir enerji kaynağı
olarak kullanamadığını göstermiştir. Bu çalışmada, insan meme
kanseri hücrelerinin birincil enerji kaynağı olarak keton cisimlerini
kullanamayacağını varsaydık ve keton cisimlerinin hücre canlılığı
üzerine etkisini araştırdık.
Gereç ve Yöntem: Bu çalışmada insan meme kanseri hücre hattı
(MCF-7) ve insan foreskin fibroblast hücre hattı (HFF) kullanıldı.
Her iki hücre hattında glukoz içeren ve içermeyen ortamlarda
keton cisimleri olan asetoasetat ve beta-hidroksibütiratın hücre
canlılığına etkisini inceledik.
Bulgular: Keton cisimlerini içeren ortamda MCF-7
hücrelerinde hücre canlılığı kontrol ortamı ile karşılaştırıldığında
azalırken, kontrol olarak kullanılan HFF hücrelerinde herhangi bir
değişiklik görülmedi.
Sonuç: Elde edilen veriler ışığında, keton cisimlerinin
kullanılması ile gerçekleştirilecek beslenmenin meme kanseri
tedavisinde yeni bir strateji olabileceğini düşünmekteyiz.
Anahtar Kelimeler
Asetoasetat Beta-hidroksibütirat Keton cisimleri MCF-7 kanser hücreleri
Kaynakça
- Skinner R, Trujillo A, Ma X, Beierle EA. Ketone bodies inhibit the viability of human neuroblastoma cells. J Pediatr Surg 2009; 44: 212-6. doi: 10.1016/j.jpedsurg.2008.10.042
- Isidoro A, Martınez M, Fernandez P, et al. Alteration of the bioenergetic phenotype of mitochondria is a hallmark of breast, gastric, lung and oesophageal cancer. Biochem J 2004; 378: 17-20. doi:10.1042/BJ20031541
- Kiebish MA, Han X, Cheng H, et al. Cardiolipin and electron transport chain abnormalities in mouse brain tumor mitochondria: lipidomic evidence supporting the Warburg theory of cancer. J Lipid Res 2008; 49: 2545-56. doi: 10.1194/ jlr.M800319-JLR200
- Modica-Napolitano J, Singh K. Mitochondrial dysfunction in cancer. Mitochondrion 2004; 4: 755-817. doi: 10.1016/j. mito.2004.07.027
- Seyfried TN. Cancer as a metabolic disease: on the origin, management, and prevention of cancer. Hoboken, NJ: Wiley, 2012. doi: 10.1093/carcin/bgt480
- Maurer GD, Brucker DP, Baehr O, et al. Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy. BMC Cancer 2015; 11: 315. doi: 10.1186/1471- 2407-11-315
- Poff AM, Ari C, Arnold P, Seyfried TN, D’Agostino DP. Ketone supplementation decreases tumor cell viability and prolongs survival of mice with metastatic cancer. Int J Cancer 2014; 135: 1711-20. doi: 10.1002/ijc.28809
- Branco AF, Ferreira A, Simões RF, et al. Ketogenic diets: from cancer to mitochondrial diseases and beyond. Eur J Clin Invest 2016; 46: 285-98. doi: 10.1111/eci.12591
- Aykin-Burns N, Ahmad IM, Zhu Y, Oberley LW, Spitz DR. Increased levels of superoxide and H2O2 mediate the differential susceptibility of cancer cells versus normal cells to glucose deprivation. Biochem J 2009; 418: 29-37. doi: 10.1042/BJ20081258
- Wu GY, Thompson JR. The effect of ketone bodies on alanine and glutamine metabolism in isolated skeletal muscle from the fasted chick. Biochem J 1988; 255: 139-44.
- Schumacker P. Reactive oxygen species in cancer cells: live by the sword, die by the sword. Cancer Cell 2006; 10: 175- 81. doi: 10.1016/j.ccr.2006.08.015
- Veech RL, Chance B, Kashiwaya Y, et al. Ketone bodies, potential therapeutic uses. IUBMB Life 2001; 51: 241-7. doi: 10.1080/152165401753311780
- Noh HS, Hah YS, Nilufar R, et al. Acetoacetate protects neuronal cells from oxidative glutamate toxicity. J Neurosci Res 2006; 83: 702-9. doi: 10.1002/jnr.20736.
- Cos S, Recio J, Sánchez-Barceló EJ. Modulation of the length of the cell cycle time of MCF-7 human breast cancer cells by melatonin. Life Sci 1996; 58: 811-6.
- Martinez-Outschoorn U, Lin Z, Whitaker-Menezes D, et al. Ketone bodies and two-compartment tumor metabolism. Cell Cycle 2012; 11: 21, 3956-63. doi: 10.4161/cc.22137.
Yıl 2018,
Cilt: 31 Sayı: 2, 57 - 60, 05.06.2018
Öz
Objective: Cancer cells exhibit an elevated glycolytic phenotype
under aerobic conditions, which is known as the Warburg effect.
Recent studies have also shown that cancer cells are glucosedependent
and cannot use ketone bodies as a primary source of
energy. In this study, we have investigated the effects of ketone
bodies on viability of breast cancer cells considering that breast
cancer cells would not use ketone bodies as a primary energy
source.
Materials and Methods: In this study we have used MCF-7
cells, which are breast cancer cells that cannot use ketone bodies
as a primary energy source and human foreskin fibroblast cells
(HFF) as controls. We measured cell viability in both cells cultured
in the presence or absence of glucose as well as the ketone bodies
acetoacetate and beta-hydroxybutyrate.
Results: Cell viability was significantly decreased in response
to ketone bodies compared with control media in MCF-7 cells
whereas in control cells (HFF) cell viability was not changed.
Conclusion: In light of the data obtained, we suggest that
dietary manipulation with the use of ketone bodies may be a new
therapeutic strategy for breast cancer.
Anahtar Kelimeler
Acetoacetate Beta-hydroxybutyrate ketone bodies MCF-7 cancer cells
Kaynakça
- Skinner R, Trujillo A, Ma X, Beierle EA. Ketone bodies inhibit the viability of human neuroblastoma cells. J Pediatr Surg 2009; 44: 212-6. doi: 10.1016/j.jpedsurg.2008.10.042
- Isidoro A, Martınez M, Fernandez P, et al. Alteration of the bioenergetic phenotype of mitochondria is a hallmark of breast, gastric, lung and oesophageal cancer. Biochem J 2004; 378: 17-20. doi:10.1042/BJ20031541
- Kiebish MA, Han X, Cheng H, et al. Cardiolipin and electron transport chain abnormalities in mouse brain tumor mitochondria: lipidomic evidence supporting the Warburg theory of cancer. J Lipid Res 2008; 49: 2545-56. doi: 10.1194/ jlr.M800319-JLR200
- Modica-Napolitano J, Singh K. Mitochondrial dysfunction in cancer. Mitochondrion 2004; 4: 755-817. doi: 10.1016/j. mito.2004.07.027
- Seyfried TN. Cancer as a metabolic disease: on the origin, management, and prevention of cancer. Hoboken, NJ: Wiley, 2012. doi: 10.1093/carcin/bgt480
- Maurer GD, Brucker DP, Baehr O, et al. Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy. BMC Cancer 2015; 11: 315. doi: 10.1186/1471- 2407-11-315
- Poff AM, Ari C, Arnold P, Seyfried TN, D’Agostino DP. Ketone supplementation decreases tumor cell viability and prolongs survival of mice with metastatic cancer. Int J Cancer 2014; 135: 1711-20. doi: 10.1002/ijc.28809
- Branco AF, Ferreira A, Simões RF, et al. Ketogenic diets: from cancer to mitochondrial diseases and beyond. Eur J Clin Invest 2016; 46: 285-98. doi: 10.1111/eci.12591
- Aykin-Burns N, Ahmad IM, Zhu Y, Oberley LW, Spitz DR. Increased levels of superoxide and H2O2 mediate the differential susceptibility of cancer cells versus normal cells to glucose deprivation. Biochem J 2009; 418: 29-37. doi: 10.1042/BJ20081258
- Wu GY, Thompson JR. The effect of ketone bodies on alanine and glutamine metabolism in isolated skeletal muscle from the fasted chick. Biochem J 1988; 255: 139-44.
- Schumacker P. Reactive oxygen species in cancer cells: live by the sword, die by the sword. Cancer Cell 2006; 10: 175- 81. doi: 10.1016/j.ccr.2006.08.015
- Veech RL, Chance B, Kashiwaya Y, et al. Ketone bodies, potential therapeutic uses. IUBMB Life 2001; 51: 241-7. doi: 10.1080/152165401753311780
- Noh HS, Hah YS, Nilufar R, et al. Acetoacetate protects neuronal cells from oxidative glutamate toxicity. J Neurosci Res 2006; 83: 702-9. doi: 10.1002/jnr.20736.
- Cos S, Recio J, Sánchez-Barceló EJ. Modulation of the length of the cell cycle time of MCF-7 human breast cancer cells by melatonin. Life Sci 1996; 58: 811-6.
- Martinez-Outschoorn U, Lin Z, Whitaker-Menezes D, et al. Ketone bodies and two-compartment tumor metabolism. Cell Cycle 2012; 11: 21, 3956-63. doi: 10.4161/cc.22137.
Toplam 15 adet kaynakça vardır.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Klinik Tıp Bilimleri |
| Bölüm | Makaleler |
| Yazarlar | |
| Yayımlanma Tarihi | 5 Haziran 2018 |
| Yayımlandığı Sayı | Yıl 2018 Cilt: 31 Sayı: 2 |