MOLT-3 leukemia

Two new cyclic heptapeptides, scytalidamides A 43 and B 44, were isolated from the culture broth of a marine fungus, Scytalidium sp., collected from the Bahamas. Compounds 43 and 44 showed moderate in vitro cytotoxicity toward HCT-116 human colon adenocarcinoma with IC50 values of 2.7 and 11.0 pM, respectively. Both compounds displayed moderate cytotoxicity in the NCI 60 cell-line panel with mean GI50 values of 7.9 and 4.1 pM for 43 and 44, respectively. The most sensitive cell lines were MOLT-4 leukemia (3.0 pM) for 43 and Uacc-257 melanoma (1.2 pM) for 44. The total syntheses of scytalidamide A 43 was achieved on solid phase using two different resins, a phenylalanine silane resin and a 4-methoxybenzaldehyde backbone linker resin. ... 

Antitumor activity testxytotoxity towards HL-60 and MOLT-4 leukemia cells... 

The mechanism of inhibition has not been characterized, but it is probably related to the ionophoretic properties of these antibiotics. Monensin has been shown to inhibit the intracellular transport of viral membrane proteins of cells infected with Semliki Forest vims (169). The formation of syncytia, normally observed when T-lymphoblastoid cell line (CEM) cells are cocultivated with human immunodeficiency vims (HlV-l)-infected T-ceU leukemia cell line (MOLT-3) cells, was significantly inhibited in the presence of monensin (170). This observation suggests that the viral glycoproteins in the treated cells were not transported to the cell surface from the Golgi membrane. 

In order to evaluate the in vitro antitumor activity of the prodrugs, compounds 20 and 21 were incubated at varied concentrations with human T-lineage acute lymphoblastic leukemia MOLT-3 cells in the presence or absence of ImM of PGA. The data from the cell proliferation assays are presented in Fig. 5.15. 

Mertens-Talcott SU, Talcott S T and Percival S S. 2003. Low concentrations of quercetin and ellagic acid synergistically influence proliferation, cytotoxicity and apoptosis in MOLT-4 human leukemia cells. J Nutr 133(8) 2669-2674. 

Schwartz GK, Arkin H, Holland JF, Ohnuraa T (1991) Protein kinase C activity and multidrug resistance in MOLT-3 human lymphoblastic leukemia cells resistant to trimetrexate. Cancer Res 51 55-61... 

Apoptosis induction. The exposure of human lymphoid leukemia Molt 4B cells to sesamolin, a component of sesame seed, produced growth inhibition and the induction of apoptosis " ". 

Miyahara, Y., H. Hibasami, H. Kat-suzaki, K. Imai, and T. Komiya. Sesamolin from sesame seed inhibits proliferation by inducing apoptosis in human lymphoid leukemia Molt 4B cells. IntJMolMed 2001 7(4) 369-371. 

Several groups have used this reaction in recent years to prepare biologically active molecules. Benzothiophene derivatives 93, prepared from Gewald products 92 in three steps via a palladium-mediated aromatization reaction, (Scheme 21) were tested for their antiproliferative activity and inhibition of tubulin polymerization [55]. Several compounds showed inhibitory effects against murine leukemia (L1210), murine mammary carcinoma (FM3A) and human T-lymphoblastoid (Molt/4 and GEM) cells. For most of the compounds, there was a positive... 

FIGURE 18.9 Concentration-effect curves for the thiopurine analogs, mercaptopurine (MP, open symbols) and thioguanine (TG, closed symbols). Effect is the percentage of cells killed in vitro relative to an untreated control in MOLT 4 (squares), CCRF-CEM (ti iangles), and Wilson (cn des) leukemia cell lines. TG is 10-fold more potent than is MP. (Reproduced with permission from Adamson PC, Poplack DG, Balis EM. Leukemia Res 1994 18 805-10.)... 

Knowles and Milner, 2000). Furthermore, these compounds are thought to be involved in the inhibition of certain cytochrome P-450 enzyme-dependent bioactivations of procarcinogens and protoxicants (Brady et al., 1991), as well as to increase levels of glutathione-S-transferase (GST), an enzyme of particular importance in the detoxification of xenobiotics in the body (Wilce and Parker, 1994). Most recently, the ability of various plants and plant extracts to influence apoptosis, or programmed cell death, in cancerous cells in an attempt to arrest their proliferation, has been the topic of much research. Allicin has been shown to induce apoptosis in a variety of cell lines, including human hepatocellular carcinoma cells (KIM-1) and human lymphoid leukemia (MOLT-4B) cells (Thatte et al., 2000). 

A new cholestane glycoside (18) with a benzoyl-rhamnoglucosyl moiety isolated from Ornithogalum saundersiae strongly inhibited in vitro the growth of human promyelocytic leukemia HL-60 cells and human T-lymphocytes leukemia MOLT-4 cells with IC50 of 21 and 18 nM... 

It was reported licochalcone A inhibits the cytopathic activity of human immunodeficiency virus (HIV) by Okuda s group [22], A cell line named OKM-1, sensitive to the cytopathic activity of HIV, was established from the peripheral blood of a patient with adult T-cell leukemia. Giant cells due to the cytopathic activity, were formed within a day on co-culture with HIV-infected Molt-4 cell (OKM-1 OKM-4 = 3 1). Licochalcone A inhibited the giant cell formation at concentration 20 ig/ml without observable cytotoxicity. Besides, licochalcone A has a radical scavenging effect, inhibition of leukotriene synthesis in human polymorphonuclear neutrophils and xanthine oxidase. 

THP-1 (monocytic leukemia) MOLT-4 (T-cell lymphoma) CCR-CEM (T-cell lymphoma) CCRF-SB (B-cell lymphoma) HL-60 (promyelocytic leukemia) U-937 (promonocytic leukemia) Raji (Burkitt lymphoma) RPMI1788 (lymphoma)... 

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