Inhibitory Effect of Curcumin on WT1 Gene Expression in Patient Leukemic Cells

  • Anuchapreeda, Songyot (Division of Clinical Microscopy, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University) ;
  • Limtrakul, Pornngarm (Department of Biochemistry, Faculty of Medicine, Chiang Mai University) ;
  • Thanarattanakorn, Pattra (Department of Pediatrics, Faculty of Medicine, Chiang Mai University) ;
  • Sittipreechacharn, Somjai (Department of Pediatrics, Faculty of Medicine, Chiang Mai University) ;
  • Chanarat, Prasit (Division of Clinical Microscopy, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University)
  • Published : 2006.01.01

Abstract

Leukemias are common worldwide. Wilms'tumor1 (WT1) protein is highly expressed in leukemic blast cells of myeloid and lymphoid origin. Thus, WT1 mRNA serves as a tumor marker for leukemias detection and monitoring disease progression. Curcumin is well known for its anticancer property. The objective of this study was to investigate the effect of curcumin on WT1 gene expression in patient leukemic cells. The leukemic cells were collected from 70 childhood leukemia patients admitted at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand, in the period July 2003 to February 2005. There were 58 cases of acute lymphoblastic leukemia (ALL), 10 cases of acute myeloblastic leukemia (AML), and 2 cases of chronic myelocytic leukemia (CML). There were 41 males and 29 females ranging from 1 to 15 years old. Leukemic cells were cultured in the presence or absence of 10 mM curcumin for 48 h. WT1 mRNA levels were determined by RT-PCR. The result showed that curcumin reduced WT1 gene expression in the cells from 35 patients (50%). It affected the WT1 gene expression in 4 of 8 relapsed cases (50%), 12 of 24 cases of drug maintenance (50%), 7 of 16 cases of completed treatment (44%), and 12 of 22 cases of new patients (54%). The basal expression levels of WT1 gene in leukemic patient cells as compared to that of K562 cells were classified as low level (1-20%) in 6 of 20 cases (30%), medium level (21-60%) in 12 of 21 cases (57%), and high level (61-100%) in 17 of 23 cases (74%). In summary, curcumin decreased WT1 mRNA in patient leukemic cells. Thus, curcumin treatment may provide a lead for clinical treatment in leukemic patients in the future.

Keywords

References

  1. Alley, M. C. and Scudiero, D. A., Monks A: Feasibility of drug screening with panels of human tumour cell lines using a microculture tetrazolium assay. Cancer Res., 48, 589-601 (1988)
  2. Ammon, H. P. T. and Wahl, M. A., Pharmacology of Curcuma longa. Planta Med., 57, 1-7 (1991) https://doi.org/10.1055/s-2006-960004
  3. Anuchapreeda, S., Leechanachai, P., Smith, M., Ambudkar, S. V., and Limtrakul, P., Modulation of P-glycoprotein expression and function by curcumin in Multidrug resistant human KB cells. Biochem. Pharmacol., 64, 573-582 (2002) https://doi.org/10.1016/S0006-2952(02)01224-8
  4. Bergmann, L., Miething, C., Maurer, U., Brieger, J., Karakas, T., Weidmann, E., and Hoelzer, D., High level of Wilms' tumor gene (WT) mRNA in acute myeloid leukemia are associated with a worse long-term outcome. Blood, 90, 1217-1225 (1997)
  5. Dovoix, A., Morcean, F., Delhalle, S., Schmitz, M., Schnekenburger, M., Galteau, M. M., Dicota, M., and Diederich, M., Inhibition of apoptosis by curcumin mediation by glutathione Stransferase P1-1 inhibition. Biochem. Pharmacol., 66, 1475- 1483 (2003) https://doi.org/10.1016/S0006-2952(03)00145-X
  6. Fraizer, G. C., Patmasiriwat, P., Zhang, X. H., and Saunders, G. F., Expression of the tumour suppressor gene WT1 in both human and bone marrow. Blood, 86, 4704-4706 (1995)
  7. Govindarajan, V. S., Turmeric: Chemistry, technology and quality. CRC Crit. Rev. Food Sci. Nutr., 12, 199-301 (1990) https://doi.org/10.1080/10408398009527278
  8. Inoue, K., Sugiyama, H., Ogawa, H., Nakagawa, M., Yamagami, T., Miwa, H., Kita, K., Hiraoka, A., Masaoka, T., Nasu, K., Kyo, T., Dohy, H., Nakauchi, H., Ishidate, T., Akiyama, T., and Kishimoto, T., WT1 as a new prognostic factor and a new marker for the detection of minimal residual disease in acute leukemia. Blood, 84, 3071-3079 (1994)
  9. Kunchandy, E. and Rao, M. N. A., Oxygen radical scarvenging activity of curcumin. Int. J. Pharm., 58, 237-240 (1990) https://doi.org/10.1016/0378-5173(90)90201-E
  10. Kuo, M. L., Huang, T. S., and Lin, J. K., Curcumin, an antioxidant and antitumor promoter, induces apoptosis in human leukemia cells. Biochim. Biophys. Acta, 1317, 95-100 (1996) https://doi.org/10.1016/S0925-4439(96)00032-4
  11. Limtrakul, P., Anuchapreeda, S., Lipigorngoson, S., and Dunn, F. W., Inhibition of carcinogen induced c-Ha-ras and c-fos proto-oncogenes expression by dietary curcumin. BMC Cancer, 1, 1-7 (2001) https://doi.org/10.1186/1471-2407-1-1
  12. Limtrakul, P., Chearwae, W., and Anuchapreeda, S., The effect of curcumin on the proliferation of cancer cell lines. Chiang Mai Med. Bull., 38, 55-61 (1999)
  13. Limtrakul, P., Lipigorngoson, S., Namwong, O., Apisariyakul, A., and Dunn, F. W., Inhibitory effect of dietary curcumin on skin carcinogenesis in mice. Cancer Lett., 116, 197-203 (1997) https://doi.org/10.1016/S0304-3835(97)00187-0
  14. Lorvidhaya, V. and Srisukho, S., Annual report 1999
  15. Lorvidhaya, V. and Srisukho, S., Chiang Mai Cancer registry, Academic-Publishing Unit, Faculty of Medicine, Chiang Mai University: Chiang Mai., 23, 51 (2002)
  16. Miwa, H., Beran, M., and Saunders, G. F., Expression of Wilms' tumor gene in human leukemias. Leukemia, 6, 405-409 (1992)
  17. Miyaki, T., Ahuji, H., Kubota, T., Kubonishi, I., Koeffler, H. P., and Miyoshi, I., Expression of candidate Wilms' tumor gene, WT1, in human leukemia cells. Leukemia, 7, 970-977 (1993)
  18. Nagabhushan, M., Amonkar, A. J., and Bhide, S. V., In vitro antimutagenicity of curcumin against environmental mutagens. Food Chem. Toxicol., 25, 545-547 (1987) https://doi.org/10.1016/0278-6915(87)90207-9
  19. Oji, Y., Ogawa, H., Tamaki, H., Oka, Y., Tsuboi, A., Kim, E. H., Soma, T., Tatekawa, T., Kawamaki, M., Asada, M., Kishimoto, T., and Sugiyama, H., Expression of Wilms' tumor gene WT1 in solid tumors and its involment in tumor cell growth. Jpn. J. Cancer Res., 90, 194-204 (1999) https://doi.org/10.1111/j.1349-7006.1999.tb00733.x
  20. Patmasiriwat, P., Fraizer, G. C., Claxton, D., Kantarjian, H., and Saunders, G. F., Expression of WT1 and GATA-1 in AML with chromosome 16q22 abnormalities. Leukemia, 10, 1127-1133 (1996)
  21. Phelan, S. A., Lindberg, C., and Call, K. M., Wilms' tumor gene, WT1, mRNA is down-regulated during induction of erythroid and megakaryocytic differentiation of K562 cells. Cell Growth Differ., 5, 677-686 (1994)
  22. Qureshi, S., Shah, A. H., and Ageel, A. M., Toxicity studies on Alpinia galanga and Curcuma longa. Planta Med., 58, 124- 127 (1992) https://doi.org/10.1055/s-2006-961412
  23. Rao, C. V., Rivenson, A., Simi, B., and Reddy, B. S., Chemoprevention of colon cancer by dietary curcumin. Ann. NY Acad. Sci., 768, 201-204 (1995) https://doi.org/10.1111/j.1749-6632.1995.tb12122.x
  24. Rao, D. S., Sekhara, N. C., Satyanarayana, M. N., and Srinivasan, M., Effect of curcumin on serum and liver cholesterol levels in the rat. J. Nutr., 100, 1307-1315 (1970) https://doi.org/10.1017/S0007114508971336
  25. Sekiya, M., Adachi, M., Hinoda, Y., Imai, K., and Yachi, A., Down-regulation of Wilms' tumor gene (WT1) during myelomonocytic differentiation in HL60 cells. Blood, 83, 1876-1882 (1994)
  26. Shankar, T. N., Shantha, N. V., Ramesh, H. P., Murthy, I. A., and Murthy V. S., Toxicity studies on Turmeric: acute toxicity studies in rats, guinea pigs and monkeys. Indian. J. Exp. Biol., 18, 73-75 (1980)
  27. Soudamini, K. K. and Kuttan, R., Inhibition chemical carcinogenesis by curcumin. J. Ethnopharmacol., 27, 227-233 (1989) https://doi.org/10.1016/0378-8741(89)90094-9
  28. Srinivasan, M., Effect of curcumin on blood sugar as seen in a diabetic subject. Indian J. Med. Sci., 26, 269-270 (1972)
  29. Sriplung, H., Sontipong, S., Martin, N., Wiangnon, S., Vootipong, V., Cheirsilpa, A., Kanchanabat, C., and Khuhaprema, T., Cancer in Thailand. Bangkok; Medical Publisher: Bangkok, 3, Chapter II, 66-69 (2003)
  30. Sugiyama, H., Wilms' tumor gene WT1: Oncogenic function and clinical application. Int. J. Hematol., 73, 177-187 (2001) https://doi.org/10.1007/BF02981935
  31. Tamaki, H., Ogawa, H., Inoue, K., Soma, T., Yamagami, T., Miyake, S., Oka, Y., Oji, Y., Tatekawa, T., Tsuboi, A., Tagawa, S., Kitani, T., Miwa, H., Kita, K., Aozasa, K., Kishimoto, T., and Sugiyama, H., Increased expression of the Wilms' tumor gene (WT1) at relapse in acute leukemia. Blood, 88, 4396- 4398 (1996)
  32. Wu, Y. J., Fraizer, D. C., and Suanders, G. F., GATA-1 transactivates the WT1 hematopoietic specific enhancer. J. Biol. Chem., 270, 5944-5949 (1995) https://doi.org/10.1074/jbc.270.11.5944
  33. Yamagami, T., Sugiyama, H., Inoue, K., Ogawa, H., Tatekawa, T., Hirata, M., Kudoh, T., Akiyama, T., Murakami, A., Maekawa, T., and Kishimoto, T., Growth inhibition of human leukemic cells by WT1 (Wilms' tumor gene) antisense oligodeoxynucleotides: Implications for the involvement of WT1 in leukemogenesis. Blood, 87, 2878-2884 (1996)
  34. Ye, Y., Raychaudhuri, B., Gurney, A., Campbell, C. E., and Williams, B. R., Regulation of WT1 by phosphorylation: inhibition of DNA binding, alteration of transcriptionalactivity and cellular translation. EMBO J., 15, 5606-5615 (1996)