Disease relevance of aclarubicin

• Aclarubicin treatment restores SMN levels to cells derived from type I spinal muscular atrophy patients [1].
• The inhibition was significant over a wide range of aclarubicin concentrations (3 nM to 0.4 microM), above which the toxicity of aclarubicin became apparent [2].
• Antagonistic effect of aclarubicin on daunorubicin-induced cytotoxicity in human small cell lung cancer cells: relationship to DNA integrity and topoisomerase II [3].
• Transplantability and sensitivity to natural killer cells of aclarubicin-resistant murine lymphoma [4].
• Aclacinomycin A (aclarubicin) is an anthracycline anticancer agent with demonstrated activity against both leukemias and solid tumors [5].

High impact information on aclarubicin

• Here, we report three compounds (sodium vanadate, trichostatin A and aclarubicin) that effectively enhance SMN2 expression by inducing Stat5 activation in SMA-like mouse embryonic fibroblasts and human SMN2-transfected NSC34 cells [6].
• We show that aclarubicin effectively induces incorporation of exon 7 into SMN2 transcripts from the endogenous gene in type I SMA fibroblasts as well as into transcripts from a SMN2 minigene in the motor neuron cell line NSC34 [1].
• We have demonstrated previously that the intercalating drug aclarubicin and the cardioprotecting agent ICRF-187 antagonize the cytotoxicity of etoposide in vitro [7].
• We have examined the effects of a group of DNA topoisomerase II (topo II) inhibitors, merbarone, aclarubicin, SN22995, RP60475F, and fostriecin, in CCRF-CEM cells and two sublines, CEM/VM-1 and CEM/VM-1-5, that were selected for increasing resistance to teniposide (VM-26) [8].
• Taken together, these data indicate that aclarubicin-mediated inhibition of daunorubicin-induced cytotoxicity is due mainly to a drug interaction with the nuclear enzyme topoisomerase II [3].

Chemical compound and disease context of aclarubicin

• Antagonistic effect of aclarubicin on the cytotoxicity of etoposide and 4'-(9-acridinylamino)methanesulfon-m-anisidide in human small cell lung cancer cell lines and on topoisomerase II-mediated DNA cleavage [2].
• Homoharringtonine in combination with cytarabine and aclarubicin resulted in high complete remission rate after the first induction therapy in patients with de novo acute myeloid leukemia [9].
• In our study, we incorporated aclarubicin (ACL) into cationic albumin-conjugated pegylated nanoparticle (CBSA-NP-ACL) to determine its therapeutic potential of rats with intracranially implanted C6 glioma cells [10].
• The sensitivity of eight cell lines established from treated and untreated patients with small cell carcinoma of the lung (SCCL) was tested in the clonogenic assay with 1 h and continuous exposure to aclarubicin (ACLA), adriamycin (ADR), daunorubicin (DAU) and mitoxantrone (MITO) [11].
• Cytosine arabinoside, etoposide and aclarubicin (AVA) for the treatment of acute myeloid leukemia (AML) in elderly patients [12].

Biological context of aclarubicin

• The kinetics of the effect of aclarubicin on c-myc and c-myb expression were comparable to those associated with the dimethylsulfoxide-induced granulocytic differentiation in this cell line, or to those observed following a chase with actinomycin D, 4 microM [13].
• In vivo inhibition of etoposide-mediated apoptosis, toxicity, and antitumor effect by the topoisomerase II-uncoupling anthracycline aclarubicin [14].
• We conclude that MDR1 gene expression is of significance for cellular drug resistance towards specific (MDR1-related) drugs in AML, whereas it is not of significance regarding drug resistance towards other drugs, which is the case with the anthracycline Acla [15].
• Aclarubicin inhibits phosphatidylinositol hydrolysis and contraction of rat aorta [16].
• A gene cluster from Streptomyces galilaeus involved in glycosylation of aclarubicin [17].

Anatomical context of aclarubicin

• The DNA binding of daunorubicin was slightly higher in HL-60 cells, but there was no notable variance between the cell lines for aclarubicin [18].
• Inhibitory effects of aclarubicin on nitric oxide production in aortic smooth muscle cells and macrophages [19].
• A number of hybridomas producing antibodies to plasma membrane of an aclarubicin-resistant subline of L5178Y cells were obtained [20].
• These results suggest that aclarubicin reduces the contractility of vascular smooth muscle directly [21].
• Results show that GSTP1-1 mRNA as well as protein expressions are increased during Aclarubicin (Acla)- and Doxorubicin (Dox)-induced erythroid differentiation of human K562 cells [22].

Associations of aclarubicin with other chemical compounds

• Both doxorubicin and aclarubicin markedly increased uPA accumulation in RC-K8- and H69-conditioned medium in a dose-dependent manner [23].
• These results suggest that in vitro resistance to cytarabine, melphalan, etoposide, L-asparaginase, aclarubicin and dexamethasone might represent factors that can predict response to the early course of therapy [24].
• DMSO-like rapid decrease in c-myc and c-myb mRNA levels and induction of differentiation in HL-60 cells by the anthracycline antitumor antibiotic aclarubicin [13].
• In the present study we determined the in vitro cross-resistance pattern between DNR, DOX, IDR, ACR and MIT in 48 untreated and 39 relapsed samples from children with ALL using the MTT assay [25].
• Although the data did not allow firm conclusions to be drawn on the correlation between MDR1 expression and drug resistance towards Ara-C and Mitox, the drug resistance towards Acla clearly was not correlated to, or dependent on, the MDR1 expression level of the AML blast cells [15].

Gene context of aclarubicin

• Pirarubicin was more than 4 times as active as aclarubicin in inhibiting the growth of solid tumors of K-ras 3T3 cells in nude mice, possibly reflecting a difference in anti-ras activity between the two antibiotics [26].
• Both doxorubicin and aclarubicin increased uPA mRNA levels, and induction in each case reached the maximal level 9 hr after stimulation [23].
• Treatment of HL-60 cells with aclarubicin, 50 nM, caused a rapid decrease in c-myc and c-myb mRNA levels within 1 h and 2 h, respectively [13].
• In a clonogenic assay, we found that the cytotoxicity induced by VP-16 in SCLC cells was inhibited when cells were postincubated with aclarubicin [27].
• Human hepatoma cells rich in P-glycoprotein are sensitive to aclarubicin and resistant to three other anthracyclines [28].

Analytical, diagnostic and therapeutic context of aclarubicin

• These microspheres were about 200 microns in diameter and contained 10% (w/w) aclarubicin [29].
• Aclarubicin-loaded cationic albumin-conjugated pegylated nanoparticle for glioma chemotherapy in rats [10].
• The addition of aclarubicin at any time in relation to VP-16 was able to stop further cytotoxicity induced by the topoisomerase II (topo-II) targeting drug [27].
• A total of 40 patients with recurrent non-Hodgkin's lymphoma were treated with ABEP combination chemotherapy (aclarubicin, N4-behenoyl-1-beta-D-arabinofuranosylcytosine, etoposide, and prednisolone) [30].
• Among the hybridoma antibodies, one was found by agglutination tests to react with the aclarubicin-resistant cell line, but not significantly with the parental and adriamycin-, bleomycin- and macromomycin-resistant cell lines [20].

References