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Chemical Compound Review

AC1NUQ3A     [3-hydroxy-2-methyl-6- [[(1S,3R)-3,5,12...

Synonyms: NSC123127
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Disease relevance of NCI60_000547


High impact information on NCI60_000547

  • The effect on cultured cells suggested that KW2152 was not cross-resistant to Adriamycin (ADM) but was cross-resistant to mitomycin C (MMC); however, KW2152 caused prolongation of life span against mice bearing P388/ADM or P388/MMC [6].
  • It was previously shown that a decreased uptake accounts for the cross-resistance of these cells to AD and ADM which then suggested that the 9-OH-E-resistant cells might display some of the properties usually associated with the multidrug resistance phenotype [7].
  • 9-OH-Ellipticine (9-OH-E)-resistant cells are not only resistant to the DNA topoisomerase II inhibitors, but also to some other antitumor agents, such as actinomycin D (AD), adriamycin (ADM), daunorubicin and vincristine [7].
  • The correlations of the chemosensitivity results were 73.9% for ADM, 73.9% for MMC, 82.6% for DDP and 60.9% for 5-FU [8].
  • However, the percentages of apoptotic cells were 5.6% (medium alone), 75.9% (CDDP), 20.0% (CPM), 22.2% (ADM), 20.5% (VCR) and 13.1% (MTX) [9].

Chemical compound and disease context of NCI60_000547


Biological context of NCI60_000547

  • Estradiol in MDA-MB-231 cells similarly increased the IC50 values for ADM (9.5-fold), MMC (15.6-fold), and TXL (2.4-fold) [1].
  • The results obtained indicate that ADM, CH and EDTA are able to induce micronuclei at meiosis [3].
  • The upregulation of iNOS gene and protein may be somehow correlated with morphological changes seen in heart of rat treated with ADR [11].
  • In rabbits with VX2 tumor in the liver we compared plasmatic and cellular pharmacokinetics of ADM and THP after i.v. and IAH therapy [12].
  • These results suggest that genistein enhances necrotic-like cell death of the breast cancer cells through the inactivation of HER-2 receptor and Akt in combination with ADR [10].

Anatomical context of NCI60_000547

  • In a clonogenic assay it was observed that TAM (1-10 microM) significantly enhanced the activity of MXN in the MCF-7/ADR but not in the drug-sensitive cell line [13].
  • Myocardium exhibited intensive morphological changes after 8 weeks of ADR treatment [11].

Associations of NCI60_000547 with other chemical compounds


Gene context of NCI60_000547

  • MMC, ADM and CTX had a significant enhancing effect on the unclamped TCD50 [14].
  • For ADM, there were no differences in plasma and heart concentrations, with only a slight increase in tumoral levels after IAH compared to i.v. administration; on the other hand, with IAH THP, there was important reduction in systemic exposure with a major increase in tumoral drug distribution [12].

Analytical, diagnostic and therapeutic context of NCI60_000547


  1. Rationale for sequential tamoxifen and anticancer drugs in adjuvant setting for patients with node- and receptor-positive breast cancer. Kim, R., Tanabe, K., Emi, M., Uchida, Y., Osaki, A., Toge, T. Int. J. Oncol. (2005) [Pubmed]
  2. Association of nitric oxide production and apoptosis in a model of experimental nephropathy. Ozen, S., Usta, Y., Sahin-Erdemli, I., Orhan, D., Gumusel, B., Yang, B., Gursoy, Y., Tulunay, O., Dalkara, T., Bakkaloglu, A., El-Nahas, M. Nephrol. Dial. Transplant. (2001) [Pubmed]
  3. Further evidence for the aneuploidogenic properties of chelating agents: induction of micronuclei in mouse male germ cells by EDTA. Russo, A., Levis, A.G. Environ. Mol. Mutagen. (1992) [Pubmed]
  4. Effect of different doses of aluminium hydroxide on renal deterioration and nutritional state in experimental chronic renal failure. Sanai, T., Okuda, S., Onoyama, K., Motomura, K., Osato, S., Hori, K., Iseki, K., Fujishima, M. Mineral and electrolyte metabolism. (1991) [Pubmed]
  5. Expression and intracellular localization of heat shock proteins in multidrug resistance of a cisplatin resistant human ovarian cancer cell line. Kamishima, T., Fukuda, T., Yoshiya, N., Suzuki, T. Cancer Lett. (1997) [Pubmed]
  6. Antitumor activity of a novel antitumor antibiotic, quinocarmycin citrate (KW2152). Fujimoto, K., Oka, T., Morimoto, M. Cancer Res. (1987) [Pubmed]
  7. Effects of verapamil on the cellular accumulations and toxicity of several antitumor drugs in 9-hydroxy-ellipticine-resistant cells. Delaporte, C., Charcosset, J.Y., Jacquemin-Sablon, A. Biochem. Pharmacol. (1988) [Pubmed]
  8. Comparison between succinate dehydrogenase inhibition test and subrenal capsule assay for chemosensitivity testing. Anai, H., Maehara, Y., Kusumoto, H., Sugimachi, K. Oncology (1987) [Pubmed]
  9. Cisplatin (CDDP) specifically induces apoptosis via sequential activation of caspase-8, -3 and -6 in osteosarcoma. Seki, K., Yoshikawa, H., Shiiki, K., Hamada, Y., Akamatsu, N., Tasaka, K. Cancer Chemother. Pharmacol. (2000) [Pubmed]
  10. Genistein, a soy isoflavone, enhances necrotic-like cell death in a breast cancer cell treated with a chemotherapeutic agent. Satoh, H., Nishikawa, K., Suzuki, K., Asano, R., Virgona, N., Ichikawa, T., Hagiwara, K., Yano, T. Res. Commun. Mol. Pathol. Pharmacol. (2003) [Pubmed]
  11. Nitric Oxide Synthase Expressions in ADR-induced Cardiomyopathy in Rats. Liu, B., Li, H., Qu, H., Sun, B. J. Biochem. Mol. Biol. (2006) [Pubmed]
  12. Intra-arterial hepatic chemotherapy with pirarubicin. Preclinical and clinical studies. Rougier, P., Munck, J.N., Elias, D., Herait, P., Bognel, C., Gosse, C., Lasser, P. Am. J. Clin. Oncol. (1990) [Pubmed]
  13. Effect of tamoxifen on mitoxantrone cytotoxicity in drug-sensitive and multidrug-resistant MCF-7 cells. Desai, P.B., Bhardwaj, R., Damle, B. Cancer Chemother. Pharmacol. (1995) [Pubmed]
  14. Effect of cancer chemotherapy on the hypoxic fraction of a solid tumor measured using a local tumor control assay. Grau, C., Overgaard, J. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. (1988) [Pubmed]
  15. Triplet state characteristics and singlet oxygen generation properties of anthracyclines. Andreoni, A., Land, E.J., Malatesta, V., McLean, A.J., Truscott, T.G. Biochim. Biophys. Acta (1989) [Pubmed]
  16. One-electron reduction of quinones by the neuronal nitric-oxide synthase reductase domain. Matsuda, H., Kimura, S., Iyanagi, T. Biochim. Biophys. Acta (2000) [Pubmed]
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