All-trans retinoic acid effect on the apoptosis gene expression of gastric cancer cell
Main Article Content
Abstract
Apoptosis occurs in multicellular organisms to control the number of cells. Apoptosis is tightly controlled by a set of protein and aberrant regulation of apoptosis may promote the formation of cancer cells. All-trans retinoic acid (ATRA) is considered to be a potent agent in the treatment of solid tumors, including gastric cancer, because of its ability to activate apoptosis. In this study, we analysed the effect of ATRA to the expression of gene encoding apoptosis suppressing or apoptosis promoting proteins by Real-time RT-PCR (RT-qPCR) method. The results showed ATRA not only down-regulated apoptosis suppressing genes including AKT1, BAD, NUP62, BCL2, PIK3R2 and MAPK1 but also up-regulated apoptosis promoting genes including CASP9, FOXO3, IL2 and TP53.
Keywords:
ATRA, apoptosis, gastric cancer, RT-qPCR
References
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[6] Fujii T., Yokomori T., A clinical study of vitamin A concerning auxiliary chemotherapies after operation of gastric cancer, Gan to Kagaku Ryoho 18 (1991) 265.
[7] Fang J.Y., Xiao S.D., Effect of trans-retinoic acid and folic acid on apoptosis in human gastric cell line MKN-45 and MKN-28, Gastroenterol 33 (1998) 656.
[8] Adachi M., & Imai K., The proapoptotic BH3-only protein BAD transduces cell death signals independently of its interaction with Bcl-2, Cell death and differentiation 9(11) (2002) 1240.
[9] Kinoshita Y., Kalir T., Rahaman J., Dottino P. & Kohtz D.S., Alterations in nuclear pore architecture allow cancer cell entry into or exit from drug-resistant dormancy, Am. J. Pathol, 180 (2012) 375.
[10] Zhang J., Zhang Z., Zhang D. Y., Zhu J., Zhang T., & Wang C., microRNA 126 inhibits the transition of endothelial progenitor cells to mesenchymal cells via the PIK3R2-PI3K/Akt signalling pathway, PloS one 8(12) (2013) e83294.
[11] Hoshino R., Tanimura S., Watanabe K., Kataoka T., & Kohno M., Blockade of the extracellular signal-regulated kinase pathway induces marked G1 cell cycle arrest and apoptosis in tumor cells in which the pathway is constitutively activated up-regulation of p27Kip1, Journal of Biological Chemistry 276(4) (2001) 2686.
[12] Persaud S.D. et al., All trans-retinoic acid analogs promote cancer cell apoptosis through non-genomic Crabp1 mediating ERK1/2 phosphorylation, Sci. Rep. 6 (2016) 22396.
[13] Fahrenkrog B., The nuclear pore complex, nuclear transport, and apoptosis This paper is one of a selection of papers published in this Special Issue, entitled The Nucleus: A Cell Within A Cell, Canadian journal of physiology and pharmacology 84(3-4) (2006) 279.
[14] Haupt S., Berger M., Goldberg Z., & Haupt Y., Apoptosis-the p53 network, Journal of cell science 116(20) (2003) 4077.
[15] Zhang X., Tang N., Hadden T.J., & Rishi A.K., Akt, FoxO and regulation of apoptosis, Biochimica et Biophysica Acta (BBA)-Molecular Cell Research 1813(11) (2011) 1978.
[16] Sakoe Y., Sakoe K., Kirito K., Ozawa K., & Komatsu N., FOXO3A as a key molecule for all-trans retinoic acid–induced granulocytic differentiation and apoptosis in acute promyelocytic leukemia, Blood, 115(18) (2010) 3787.
[17] Li J., Orr B., White K., Belogortseva N., Niles R., et al., Chmp 1A is a mediator of the antiproliferative effects of all-trans retinoic acid in human pancreatic cancer cells, Mol. Cancer 8:7 (2009).
[18] Zheng A, Mantymaa P, Saily M, Savolainen E, Vahakangas K, Koistinen P., p53 pathway in apoptosis induced by all-trans-retinoic acid in acute myeloblastic leukaemia cells, Acta Haematol. 103 (2000) 135.
[19] Zhang H, Rosdahl I., Expression profiles of p53, p21, bax and bcl-2 proteins in all-trans-retinoic acid treated primary and metastatic melanoma cells, Int. J. Oncol. 25 (2004) 303.
[20] Mrass P., Rendl M., Mildner M., Gruber F., Lengauer B., Ballaun C., ... & Tschachler, E., Retinoic Acid Increases the Expression of p53 and Proapoptotic Caspases and Sensitizes Keratinocytes to Apoptosis, Cancer research 64(18) (2004) 6542.
[21] Zambricki E. et al., Signaling T-cell survival and death by IL-2 and IL-15. Am. J. Transplant. Off. J. Am. Soc. Transplant, Am. Soc. Transpl. Surg. 5 (2005) 2623.