Leukemias curcumin

Liu, Y., Chang, R.L., Cui, X.X., Newmark, H.L. and Conney, A.H. 1997. Synergistic effects of curcumin on all-trans retinoic acid- and 1 alpha,25-dihydroxyvitamin D3-induced differentiation in human promyelocytic leukemia HL-60 cells. Oncol Res 9 19-29. 

Several reports have described the anticancer activity of curcumin in a variety of cancer cell lines. In vitro studies have established the activity for curcumin against breast, gastric, hepatic, pancreatic, colorectal, urinary bladder, kidney, prostate, cervical, ovarian, uterine, lung, oral, thymic, and skin cancers. Besides these cancer types, curcumin has shown in vitro therapeutic efficacy against hematological cancers including leukemia, lymphoma, and multiple myeloma. One of our early studies established that the antiproliferative effect of curcumin in human breast cancer cell lines, including hormone-dependent, hormone-independent,... 

Studies have also demonstrated curcumin s therapeutic properties in vivo. In 6-week-old mice, the administration of a 2% curcumin diet via oral gavage resulted in a 53% reduction in lymphomas and leukemias. When topically applied prior to the administration of TPA in mice, curcumin down-regulated TPA-induced NF-kB and AP-1. It was also showed that oral administration of curcumin (50-200 mg/kg) inhibits the development of leukemia (HL 60) cell-induced xenografts in nude mice [Anand et al., 2008]. 

Studies conducted by our group showed that curcumin inhibited constitutive activation of NF-kB, COX-2, and STAT3 in the PBMC from multiple myeloma patients. Curcumin was given at 2, 4, 8, 12g/day orally, which was well tolerated with no adverse events. Out of 29 patients 12 patients continued treatment for 12 weeks and 5 completed one full year of treatment with stable disease. Clinical studies performed with leukemia patients were also reported. In a study of the 70 childhood leukemia patients samples, curcumin reduced WT1 gene expression in 35 samples [Anuchapreeda et al., 2006b]. 

Chen J, Wanming D, Zhang D, Liu Q, Kang J. 2005. Water-soluble antioxidants improve the antioxidant and anticancer activity of low concentrations of curcumin in human leukemia cells. Pharmazie 60 57-61. 

Chen Y, Wu Y, He J, Chen W. 2002. The experimental and clinical study on the effect of curcumin on cell cycle proteins and regulating proteins of apoptosis in acute myelogenous leukemia. J Huazhong Univ Sci Technolog Med Sci 22 295-298. 

Mukherjee Nee Chakraborty S, Ghosh U, Bhattacharyya NP, Bhattacharya RK, Dey S, Roy M. 2007. Curcumin-induced apoptosis in human leukemia cell HL-60 is associated with inhibition of telomerase activity. Mol Cell Biochem 297 31-39. 

Pae HO, Jeong SO, Jeong GS, Kim KM, Kim HS, Kim SA, Kim YC, Kang SD, Kim BN, Chung HT. 2007. Curcumin induces pro-apoptotic endoplasmic reticulum stress in human leukemia HL-60 cells. Biochem Biophys Res Common 353 1040-1045. 

Pan MH, Chang WL, Lin-Shiau SY, Ho CT, Lin JK. 2001. Induction of apoptosis by garcinol and curcumin through cytochrome c release and activation of caspases in human leukemia HL-60 cells. J Agric Food Chem 49 1464-1474. 

Rajasingh J, Raikwar HP, Muthian G, Johnson C, Bright JJ. 2006. Curcumin induces growth-arrest and apoptosis in association with the inhibition of constitutively active JAK-STAT pathway in T cell leukemia. Biochem Biophys Res Commun 340 359-368. 

Singhal SS, Awasthi S, Pandya U, Piper JT, Saini MK, Cheng JZ, Awasthi YC. 1999. The effect of curcumin on glutathione-linked enzymes in K562 human leukemia cells. Toxicol Leu 109 87-95. 

Sokoloski JA, Shyam K, Sartorelli AC. 1997. Induction of the differentiation of HL-60 promyelocytic leukemia cells by curcumin in combination with low levels of vitamin D3. Oncol Res 9 31-39. 

Tan TW, Tsai HR, Lu HF, Lin HL, Tsou MF, Lin YT, Tsai HY, Chen YF, Chung JG. 2006. Curcumin-induced cell cycle arrest and apoptosis in human acute promyelo-cytic leukemia HL-60 cells via MMP changes and caspase-3 activation. Anticancer Res 26 4361-4371. 

Tomita M, Kawakami H, Uchihara JN, Okudaira T, Masuda M, Takasu N, Matsuda T, Ohta T, Tanaka Y, Ohshiro K, Mori N. 2006. Curcumin (diferuloylmethane) inhibits constitutive active NF-kappaB, leading to suppression of cell growth of human T-cell leukemia virus type I-infected T-cell lines and primary adult T-cell leukemia cells. Int J Cancer 118 765-772. 

Based on the structure of curcumin, a series of styrylpyrazoles, styrylisoxazole, and styrylisothiazoles were synthesized and found to be dual inhibitors of COX and 5-LOX tested in rat basophilic leukemia cells. The most potent COX and 5-LOX dual inhibitor had IC50 values at 0.9 pM and 1.2 pM, respectively [159],... 

Kuo, M.L., Huang, T.S., and Lin, J.K., Curcumin, an antioxidant and antitumor promoter, induces apoptosis in human leukemia cells, Biochem. Biophys. Acta, 1317, 95, 1996. 

Dibenzoylmethane (DBM) is a minor constituent of licorice and an analogue of curcumin. We previously reported that feeding 1% DBM in the diet strongly inhibited 7,12-dimethylbenzyla[a]anthracene (DMBA)-induced mammary tumorigenesis and formation of leukemias/lymphomas in Senear mice). In this report, we show that topical application of DBM to the backs of mice inhibited chemical- and ultraviolet light (UV)-induced inflammation, sunburn lesions, and formation of skin tumors in mice. Topical application of DBM inhibited TPA-induced edema of mouse ears and skin tumor promotion in CD-I mice in a dose-dependent manner. Topical application of 3 - 10 pmol DBM with 5 nmol TPA twice weekly for 16 weeks in CD-I mice previously treated with DMBA inhibited the number of skin tumors per mouse by 65 - 93%, and percent of mice with tumors was inhibited by 29 - 50%.. Topical application of 10 pmol DBM with mirex (a non-TP A type tumor promoter) 3 times a week for 18 weeks in... 

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