Abstract

It is an effective antioxidant molecule that exhibits free radical scavenging activity and it enhances antioxidant status in rats and exhibited anticancer properties. It has been shown that α-Lipoic acid is a very effective molecule against type 2 diabetes, atherosclerosis, inflammatory skin diseases, reperfusion arrhythmias and Parkinson’s disease and serves apoptotic action in different cancer cells. These molecules can display important roles in treatment of colon cancer. In this study, we examined the synergetic effects of α-lipoic acid and L-carnitine on HCT 116 +/+ and HCT 116 -/- colon cancer cell line. For this purpose, HCT 116 +/+ and -/- colon cancer cells were treated with L-carnitine and α-Lipoic acid for 24 hours and MTT assay and caspase 3 enzyme activity assay was conducted. α -Lipoic acid and L-carnitine alone or in combination decreased cell viability in HCT 116 +/+ and /- colon cancer cells and exhibited synergetic effect on the cell viability. Further studies must be conducted to find out the mechanism of their effects in cancer therapy

Keywords

• L-carnitine, α-lipoic acid, colon cancer

L-Karnitin ve Alfa-Lipoik Asitin, HCT 116 +/+ ve -/- Kolon Kanser Hücre Serilerinin Proliferasyonu Üzerindeki Sinerjetik Etkileri

Abstract

L-karnitin, uzun zincirli yağ asitlerinin mitokondri matriksine transportunda yer alarak, lipid metabolizmasında önemli görevlere sahip olan bir molekül olmasının yanı sıra, serbest radikal temizleyici aktivite gösterir ve antikanser özellikler sergiler. α-Lipoik asitin, tip2 diyabet, ateroskleroz, inflamatuar deri hastalıkları ve Parkinson hastalığına karşı oldukça etkili bir molekül olduğu gösterilmiştir ve farklı kanser hücrelerinde apoptotik etkiler gösterdiği bilinmektedir. Bu çalışmada, α-Lipoik asit ve L-Karnitin’in, HCT 116 +/+ ve HCT 116 -/- kolon kanseri hücre serilerindeki sinerjetik etkileri araştırılmıştır. Bu amaçla, HCT 116 +/+ ve -/- kolon kanseri hücreleri, L-karnitin ve α-Lipoik asit ile 24 saat muamele edildikten sonra, MTT testi ve kaspaz 3-enzim aktivitesi ile hücre canlılığı ve kaspaz-3 enzim aktivitesi üzerindeki etkileri incelenmiştir. Bu çalışmada, α-Lipoik asit ve Lkarnitin’in, kombinasyon halinde verildiklerinde sinerjetik etkiler sergileyerek, HCT 116 +/+ ve -/- kolon kanseri hücrelerinin canlılığını azalttıkları ve kaspaz-3 enzim aktivitesini artırdıkları görülmüştür. L-karnitin ve α-Lipoik asitin kanser terapisindeki sinerjetik etkilerinin mekanizmasını açığa çıkarmak için daha ileri çalışmalar yapılmalıdır

Keywords

• L-karnitin, α-lipoik asit, kolon kanseri

References

1. Behrend, L, Henderson, G., Zwacka, R.M. 2003. Reactive oxygen species in oncogenic transformation. Biochem Soc Trans, 31, 1441–1444.
2. Bilska, A., Włodek, L.2005. Lipoic acid - the drug of the future?. Pharmacol Rep. 57(5), 570-7.
3. Dozio, E., Ruscica, M., Passafaro, L., Dogliotti, G., Steffani, L., Marthyn, P., et al. 2010. The natural antioxidant alpha-lipoic acid induces p27(Kip1)-dependent cell cycle arrest and apoptosis in MCF-7 human breast cancer cells. Eur J Pharmacol. 641, 29–34.
4. Dörsam, B., Göder, A., Seiwert, N., Kaina, B., Fahrer, J. 2015. Lipoic acid induces p53-independent cell death in colorectal cancer cells and potentiates the cytotoxicity of 5-fluorouracil. Arch Toxicol, (10), 1829-46.
5. Feuerecker, B., Pirsig, S., Seidl, C., Aichler, M., Feuchtinger, A., Bruchelt, G., et al. 2012. Lipoic acid inhibits cell proliferation of tumor cells in vitro and in vivo. Cancer Biol Ther.13, 1425–35.
6. Fujii, Y., Segawa, R., Kimura, M., Wang, L., Ishii, Y., Yamamoto, R., Morita, R., Mitsumori, K., Shibutani, M. 2013. Inhibitory effect of α-lipoic acid on thioacetamide-induced tumor promotion through suppression of inflammatory cell responses in a two-stage hepatocarcinogenesis model in rats.
7. Chem Biol Interact, 205(2),108-18. Gülçin, I. 2006. Antioxidant and antiradical activities of L-carnitine. Life Sci, 78: 803–811.
8. Hanahan, D., Weinberg Robert A. 2011. Hallmarks of cancer: the next generation. Cell,144 (5), 646–674.

9. Huang,C.Y., Yu, L.C. 2015. Pathophysiological mechanisms of death resistance in colorectal carcinoma. World J Gastroenterol, 21(41), 11777–11792.
10. Mantovani, G., Maccio, A., Madeddu, C., Mura, L., Massa, E., Gramignano, G., Lusso, M.R., Murgia, V., Camboni, P., Ferreli, L. 2003. Reactive oxygen species, antioxidant mechanisms, and serum cytokine levels in cancer patients: Impact of an antioxidant treatment. J Environ Pathol Toxicol Oncol, , 17–28. 9.
11. Marques-Vidal, P., Ravasco, P., Camilo, M.E. 2006. Foodstuffs and colorectal cancer risk: a review. Clin Nutr. 25, 14–36.
12. Michikoshi, H., Nakamura. T., Sakai, K., Suzuki, Y., Adachi, E., Matsugo, S., et al. 2013.Alpha
13. Lipoic acid-induced inhibition of proliferation and met phosphorylation in human non-small cell lung cancer cells. Cancer Lett. 335, 472–8. Mizuno, M., Packer, L. 1994. Effects of alpha-lipoic acid and dihydrolipoic acid on expression of proto-oncogene c-fos. Biochem. Biophys Res Commun, 200,1136–1142.
14. Mukherjee, A.K., Basu, S., Sarkar, N., Ghosh, A.C. 2001. Advances in cancer therapy with plant based natural products. Curr Med Chem, 8 (12), 1467–1486.
15. Na, M.H., Seo. E.Y., Kim, W.K. 2009. Effects of alpha-lipoic acid on cell proliferation and apoptosis in MDA-MB-231 human breast cells. Nutr Res Pract. 3, 265–71.
16. Newman, D.J., Cragg, G.M. 2012. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod,75 (3), 311–335.
17. Peluso G., Nicolai, R., Reda, E., Bennatti, P., Barbarisi, A., Calvani, M. 2000. Cancer and anticancer therapy-induced modifications on metabolism mediated by carnitine system. J Cell Physiol. 182, 339–350.
18. Rochette, L., Ghibu, S., Richard, C., Zeller, M., Cottin, Y., Vergely, C. 2013. Direct and indirect antioxidant properties of alpha-lipoic acid and therapeutic potential. Mol Nutr Food Res, 57(1):114–
19. Schwartz, L., Guais, A., Israel, M., Junod, B., Steyaert, J.M., Crespi, E., et al. 2013. Tumor regression with a combination of drugs interfering with the tumor metabolism: efficacy of hydroxycitrate, lipoic acid and capsaicin. Invest New Drugs. 31, 256–64.
20. Tenesa, A.D., Malcolm, G. 2009. New insights into the etiology of colorectal cancer from genome-wide association studies. Nat Rev Genet, 10 (6), 353–358.
21. Yoo, T.H., Lee, J.H., Chun, H.S., Chi, S.G. 2013. Alpha-Lipoic acid prevents p53 degradation in colon cancer cells by blocking NF-kappaB induction of RPS6KA4. Anticancer Drugs. 24, 555–65.