Leukemia promyelocytic

Imidazole antimycotics, ketoconazole, clotrimazole, and miconazole are potent inhibitors of various cytochrome P450-isoenzymes that also affect the metabolism of retinoids. They were fust shown to inhibit the metabolism of RA in F9 embryonal carcinoma cells. When tested in vitm liarazole, a potent CYP-inhibitor, suppressed neoplastic transformation and upregulated gap junctional communication in murine and human fibroblasts, which appeared to be due to the presence of retinoids in the serum component of the cell culture medium. Furthermore, liarazole magnified the cancer chemopreventive activity of RA and (3-carotene in these experiments by inhibiting RA-catabolism as demonstrated by absence of a decrease in RA-levels in the culture medium in the presence of liarazole over 48 h, whereas without liarazole 99% of RA was catabolized. In vivo, treatment with liarazole and ketoconazole reduced the accelerated catabolism of retinoids and increased the mean plasma all-irans-RA-concentration in patients with acute promyelocytic leukemia and other cancels. 

Gambacorti-Passerini C., Mologni L, Bertazzoli C., le Coutre P., Marchesi E., Grignani F., Nielsen P.E. In vitro transcription and translation inhibition by anti-promyelocytic leukemia (PML)/re-tinoic acid receptor-alpha and anti-PML peptide nucleic acid. Blood 1996 88 1411-1417. 

Mologni L., Marches E., Nielsen P.E., Gai4BACOrti-Passerini C. Inhibition of promyelocytic leukemia (PML)/retinoic acid receptor-alpha and PML expression in acute promyelocytic leukemia cells by anti-PML peptide nucleic acid. Cancer Res. 2001 61 5468-5473. 

An extract from Lactuca indica showed significant free radical scavenging activity, and protected phixl74 supercoiled DNA against strand cleavage and reduced oxidative stress in human promyelocytic leukemia HL-60 cells. On account of protocatechulic acid, methyl p-hydroxybenzoate, caffeic acid, 3,5-dicaffeoylquinic acid, luteolin 7-O-fT glucopyranoside, and quercetin 3-0-(3-g 1 ucopyranoside are the major antioxidative constituents (111). 

Martelli AM, Bortul R, Bareggi R, et al. The pro-apoptotic drug camptothecin stimulates phospholipase D activity and diacylglycerol production in the nucleus of HL-60 human promyelocytic leukemia cells. Cancer Res 1999 59 3961-3967. 

Nakatani N, Ichimaru M, Moriyasu M, Kato A. Induction of apoptosis in human promyelocytic leukemia cell line HL-60 by C-benzylated dihydrochalcones, uvaretin, isouvaretin and diuvaretin. Biol Pharm Bull 2005 28 83-86. 

Nara, E., H. Hayashi, M. Kotake, K. Miyashita, and A. Nagao. 2001. Acyclic carotenoids and their oxidation mixtures inhibit the growth of HL-60 human promyelocytic leukemia cells. Nutr Cancer 39(2) 273-283. 

The induction of differentiation may be an effective mechanism for chemoprevention of chronic diseases. It has been reported that lycopene alone induced differentiation of HL-60 promyelocytic leukemia cells (Amir et al., 1999). A similar effect was also observed for other carotenoids, including P-carotene and lutein (Liu et al., 1997 Sokoloski et al.,1997). 

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. 

Sokoloski, J.A., Hodnick, W.F., Mayne, S.T., Cinquina, C., Kim, C.S., and Sartorelli, A.C. 1997. Induction of the differentiation of HL-60 promyelocytic leukemia cells by vitamin E and other antioxidants in combination with low levels of vitamin D3 Possible relationship to NF-kappaB. Leukemia 11 1546-1553. 

Dunphy CH, Polski JM, Johns G, et al. Acute promyelocytic leukemia, hypo-granular variant, with uncharacteristic staining with chloroacetate esterase. Leak. Lymphoma 2001 42 215-219. 

HETE, 12-hydroxyeicosatetraenoic acid HL60, human promyelocytic leukemia cells... 

Classic antioxidants, vitamin E, vitamin C, and others can suppress the activation of apoptosis. For example, ascorbic acid prevented cytochrome c release and caspase activation in human leukemia cells exposed to hydrogen peroxide [128], Pretreatment with A -acctylcystcinc, ascorbate, and vitamin E decreased homocysteine thiolactone-induced apoptosis in human promyelocytic leukemia HL-60 cells [129]. Resveratrol protected rat brain mitochondria from anoxia-reoxygenation damage by the inhibition of cytochrome c release and the reduction of superoxide production [130]. However, it should be mentioned that the proapoptotic effect of ascorbate, gallic acid, or epigallocatechin gallate has been shown in the same human promyelocytic leukemia cells [131]. 

Granulocyte differentiation acute promyelocytic leukemia PBMCs (in vivo) Cultured bone marrow mononuclear cells (in vitro) All-trans retinoic acid (ATRA) Promoter analysis of ATRA response genes suggest molecular mechanism underlying ATRA-induced granulocytic differentiation [30]... 

Nauseef, W. M. (1986). Myeloperoxidase biosynthesis by a human promyelocytic leukemia cell line Insight into myeloperoxidase deficiency. Blood 67,865-72. 

Louria-Hayon, L, et al.. The Promyelocytic Leukemia Protein Protects p53 from Mdm2-mediated Inhibition and Degradation. J Biol Chem, 2003, 278(35), 33134-41. 

Macfarlane, D.E. and O Donnell, P.S., 1993, Phorbol ester induces apoptosis in HL-60 promyelocytic leukemia cells but not in HL-60 PET mutant, Leukemia 7 1846-1851. 

Transcription regulators are also known to be sumoylated. One of tbe early studies of tbis phenomenon showed that promyelocytic leukemia protein (PML) is a substrate for SUMO conjugation. Once SUMO is attached to the PML protein it is directed to a subdomain of tbe nucleus called tbe PML oncogenic domain (POD). It is thought that POD localization of the PML protein allows it to recruit other proteins such as transcription factors. Transcription factors in the POD can activate or inhibit transcription. Another transcription factor known to be sumoylated is Sp3. ° SUMO also has roles in chromatin condensation and interphase chromosome organization. ... 

Seo HJ, Surh YJ. (2001) Eupatilin, a pharmacologically active flavone derived from Artemisia plants, induces apoptosis in human promyelocytic leukemia cells. Mutat Res 496 191-198. 

Hayakawa Y, Nakagawa M, Kawai H, Tanabe K, Nakayama H, Shimazu A, Seto H, Otake N. (1983) Studies on the differentiation inducers of myeloid leukemic cells 111. Spicamycin, a new inducer of differentiation of HL-60 human promyelocytic leukemia cells. J Antibiot 36 934-937. 

Kwon SH, Ahn SH, Kim YK, Bae GU, Yoon JW, Hong S, Lee HY, Lee YW, Lee HW, Han JW. (2002) Apicidin, a histone deacetylase inhibitor, induces apoptosis and Fas/Fas ligand expression in human acute promyelocytic leukemia cells. J Biol Chem 111 2073-2080. 

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