Disease relevance of Aclacinomycin A

• For BL cells, ADM- or DHAD-induced cell lethality was also potentiated by hyperthermia; ACM produced only additive cell kill [1].
• Aclacinomycin A in acute leukaemias and lymphomas [2].
• Thirty-five patients with acute myelogenous leukemia were treated with aclacinomycin A (60 mg/m2/day for 5 days) and VP-16-213 (100 mg/m2/day for 5 days) [3].
• Sensitivity of bone marrow hematopoietic colony-forming cells from mice, dogs, and humans to carminomycin, marcellomycin, aclacinomycin A, and N,N-dibenzyldaunorubicin and its relationship to clinical toxicity [4].
• Effects on leukemic clonogenic cells in murine myeloid leukemia of 1-beta-D-arabinofuranosylcytosine and the anthracyclines adriamycin, daunomycin, aclacinomycin A, and 4'-epidoxorubicin [5].

High impact information on Aclacinomycin A

• With the MM cells, hyperthermia potentiated the cytotoxic effects of doxorubicin (ADM), daunorubicin, mitoxantrone (DHAD), and quelamycin but did not enhance that of aclacinomycin (ACM) [1].
• The resulting reporter constructs were tested in a transfection assay of the erythroleukemic cell line K562 stimulated to differentiate by treatment with the anthracycline drugs ACM and DOX or hemin (HEM) [6].
• In addition, ACM strongly activated the erythroid gene promoters that contain GATA binding sites [6].
• Effects of aclacinomycin-A (ACM) on leukemic cells and normal hematopoietic stem cells were studied for the purpose of evaluating the usefulness of this agent as an antileukemic agent [7].
• Peritoneal macrophages from mice injected with aclacinomycin (ACM) (4 mg/kg, i.p.) showed increased functional activity, as assessed by increased antitumoral activity in vitro and in vivo and zymosan-triggered chemoluminescence [8].

Chemical compound and disease context of Aclacinomycin A

• MX2, in contrast to ADM, was effective against sublines of P388 leukemia resistant to ADM or aclacinomycin A in vivo as well as in vitro [9].
• In vitro clonogenic assays utilizing a battery of adriamycin-sensitive and -resistant human ovarian carcinoma cell lines have shown that aclacinomycin A is more cytotoxic than adriamycin in all cell lines tested [10].
• In the present study, 29 patients with locally advanced cervical adenocarcinoma (bulky IB-IVB) were treated with neoadjuvant chemotherapy (NAC) using cisplatin, aclacinomycin-A and mitomycin-C, followed by radical surgery or irradiation [11].
• Assessment of the antiinvasive potential of the anthracycline aclacinomycin (Aclarubicin) in a human fibrosarcoma cell line [12].
• Calcium channel blockers also potentiate the antitumor activities of several DNA-interacting drugs, such as adriamycin, THP-adriamycin, daunomycin, aclacinomycin A, mitomycin C, actinomycin D, mitoxantrone, and nogalamycin derivatives in P388 leukemia resistant to adriamycin [13].

Biological context of Aclacinomycin A

• The kinetics of uptake by cells and nuclear incorporation of aclacinomycin A was studied in Friend leukemia cells [14].
• Uptake, efflux, and hydrolysis of aclacinomycin A in Friend leukemia cells [14].
• Effects of aclacinomycin on cell survival and cell cycle progression of cultured mammalian cells [15].
• Enhanced activity of murine peritoneal cells after aclacinomycin injection: characteristics of the enhanced respiratory burst [16].
• Tumorigenicity in vivo and induction of mutagenesis and DNA repair in vitro by aclacinomycin A and marcellomycin: structure-activity relationship and predictive value of short-term tests [17].

Anatomical context of Aclacinomycin A

• We have investigated the activation of mouse peritoneal macrophages by injection of aclacinomycin (ACM) [18].
• In vitro sensitivity of myeloblast clonogenic cells to doxorubicin, aclacinomycin A, and 4'-O-tetrapyranyl-doxorubicin: correlations with clinical responses [19].
• WEHI-3B D+ monomyelocytic leukemia cells were induced to differentiate to mature granulocytes when treated with either 30 nM aclacinomycin A or 7 microM retinoic acid [20].
• In primary rat hepatocytes, aclacinomycin A was active in inducing unscheduled DNA synthesis, whereas marcellomycin was not [17].
• The antitumor drug aclacinomycin A was previously shown to inhibit the degradation of ubiquitinated proteins in rabbit reticulocyte lysates with an IC50 of 52 microM (Isoe, T., Naito, M., Shirai, A., Hirai, R., and Tsuruo, T.(1992) Biochim. Biophys. Acta 1117, 131-135) [21].

Associations of Aclacinomycin A with other chemical compounds

• The effects of aclacinomycin (ACM; NSC 208734) on cell viability, growth, and colony formation were investigated in suspension (Friend leukemia and L1210) and adherent (Chinese hamster ovary) cell systems [15].
• HL-60/AMSA was also sensitive to the anthracycline aclacinomycin, Vinca alkaloids, and alkylating agents [22].
• Superoxide formation by NADH dehydrogenase after anthracycline treatment appeared to follow saturation kinetics with an apparent Km of 167.3, 73.3, 64.0, or 47.6 microM for doxorubicin, daunorubicin, rubidazone, or aclacinomycin A, respectively [23].
• PURPOSE: To establish a novel formulation tumor-targeted drug carrier of lipophilic antitumor antibiotics, aclacinomycin A (ACM), folate-linked microemulsions were prepared and investigated both in vitro and in vivo [24].
• The probe 4-(2'-bromoethyl)phenol showed that all three anthracyclines completely protected all of the adenines in the minor groove from alkylation, and enhanced major groove guanine alkylation was observed with aclacinomycin A, daunomycin, and, to a much lesser extent, ditrisarubicin B [25].

Gene context of Aclacinomycin A

• Nuclear transcription factor GATA-1 is activated during aclacinomycin-induced erythroid differentiation [26].
• By 12 to 18 h after aclacinomycin A exposure, the c-myc and c-myb mRNA levels had returned to about pretreatment levels [27].
• Increased expression of GATA-1 and NFE-2 erythroid-specific transcription factors during aclacinomycin-mediated differentiation of human erythroleukemic cells [28].
• In the present work, Fc gamma receptor II (CD32) expression at the K562 cell membrane was clearly decreased after aclacinomycin-treatment but was unaltered by adriamycin-treatment [29].
• When the glioma cells were incubated with the aclacinomycin A:LDL complex, cellular drug accumulation was dependent on the LDL receptor activity [30].

Analytical, diagnostic and therapeutic context of Aclacinomycin A

• We therefore investigated the early effect of the potent differentiation-inducing anthracycline antitumor antibiotic, aclacinomycin A, on the c-myc and c-myb mRNA levels in the Friend cell line, F4-6, using Northern blot analysis [27].
• The pharmacokinetic profile of aclacinomycin-A in plasma and urine was studied in 3 patients given 65 mg/m2 using a high performance liquid chromatography assay [31].
• These results indicate that the reduction of amino acid incorporation into proteins after treatment of Friend erythroleukemia cells with aclacinomycin A may be due to a reduced uptake of amino acids [32].
• Sensitive enzyme immunoassay for the quantification of aclacinomycin A using beta-D-galactosidase as a label [33].
• Aclacinomycin A, another anthracycline antibiotic, has been found to have activity against a wide variety of murine tumors and human xenografts [10].

References