New antitumor antibiotics, aclacinomycins A and B.

Oki, Taikan; Matsuzawa, Yasue; Yoshimoto, Akihiro; Numata, Kenji; Kitamura, Iwao; Hori, Senji; Takamatsu, Akira; Umezawa, Hamao; Ishizuka, Masaaki; Naganawa, Hiroshi; Suda, Hiroyuki; Hamada, Masa; Takeuchi, Tomio

doi:10.7164/antibiotics.28.830

Cited by 221 publications

(78 citation statements)

References 5 publications

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“…Development of resistance to the drugs is a major problem, and much effort is devoted to the search of new anthracyclines without cross-resistance to the parent drugs. The anthracycline aclarubicin (ACLA) was isolated in 1975 by Oki et al (1975) and activitiy was found in acute myelogenic leukaemia (AML) refractory to treatment with daunorubicin (DAU) and cytarbine (Pedersen-Bjergaard et al, 1984; Warrel et al, 1982). Recently, a phase III trial has found ACLA to be superior to DAU in the treatment of de novo AML (Hansen et al, 1988).…”

mentioning

confidence: 99%

In vitro evaluation of the potential of aclarubicin in the treatment of small cell carcinoma of the lung (SCCL)

Pb¹,

Vindeløv²,

Roed³

et al. 1989

Br J Cancer

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Summary 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). The sensitivity to ADR, DAU and MITO covariated, and varied with a factor of five. The sensitivity to ACLA was independent of the sensitivity to ADR and varied only within a factor of two. Only ACLA showed pronounced increased potency with continuous incubation, and ACLA was the most potent drug in the three cell lines least sensitive to ADR. Two resistant cell lines were selected by treating NCI-H69 in vitro with DAU. One cell line (9-fold resistant to DAU) expressed large amounts of P-glycoprotein, the other cell line (4-fold resistant to DAU) had barely detectable glycoprotein. Both lines acquired resistance to ADR, ACLA and MITO. The cross-resistance to ACLA and MITO was only partial and ACLA was still the most potent drug on these lines. The sensitivity to ACLA of the cell lines least sensitive to ADR suggest that ACLA partially circumvents mechanisms of multidrug resistance. Together with the pronounced increase in potency with prolonged exposure, these results suggest that ACLA has a mechanism of action different from the 'classical' anthracyclines. In this context mitoxantrone is more similar to the classical anthracyclines although its structure is more dissimilar.The anthracyclines are among the most potent drugs in the treatment of a wide range of human neoplasms. Development of resistance to the drugs is a major problem, and much effort is devoted to the search of new anthracyclines without cross-resistance to the parent drugs. The anthracycline aclarubicin (ACLA) was isolated in 1975 by Oki et al. (1975) and activitiy was found in acute myelogenic leukaemia (AML) refractory to treatment with daunorubicin (DAU) and cytarbine (Pedersen-Bjergaard et al., 1984; Warrel et al., 1982). Recently, a phase III trial has found ACLA to be superior to DAU in the treatment of de novo AML (Hansen et al., 1988). In a previous study on the inter-experimental variation in the clonogenic assay we observed that the sensitivity pattern to ACLA in a panel of small cell lung cancer (SCCL) cell lines was different from the sensitivity to adriamycin (ADR), DAU and mitoxantrone (MITO) after short time incubation (Jensen et al., 1989). The present investigations were initiated to further elucidate the differences between ACLA and the other analogues. A murine tumour has recently been described to be relatively more sensitive to MITO than the tested human tumours (Hill et al., 1989). The murine tumour cells P388 and Ehrlich were included in the present study for comparision to the human cell lines and the in vivo antitumour models. As the relationship between duration of drug exposure and cytotoxicity can give valuable information on mechanisms of toxicity (Roed et al., 1986), the patterns of sensitivity to ACLA, ADR, DAU and MITO after shor...

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confidence: 99%

In vitro evaluation of the potential of aclarubicin in the treatment of small cell carcinoma of the lung (SCCL)

Pb¹,

Vindeløv²,

Roed³

et al. 1989

Br J Cancer

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“…Some of them such as adriamycin 1 ) and aclacinomycin 2 ) have been used clinically and been proved to be effective for some kinds of human cancers. The most unfavorable effect of anthracyclines is, like the other chemotherapeutic agents, its toxicity against normal proliferating tissues.…”

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confidence: 99%

Differentiation Inducing Activity of Anthracycline Compounds in Friend Leukemia Cells

Tsuji

Morioka

Takezawa

et al. 1986

Agricultural and Biological Chemistry

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“…However, its use is restricted due to its cardiotoxic and undesirable side effects. In order to improve the pharmacodynamic properties of clinically-useful antitumour anthracyclines, new doxorubicin analogues that have lower toxicity but higher antitumour activity have been synthesised or isolated (Oki et al, 1975;Umezawa et al, 1979;Cassinelli et al, 1984;Weiss et al, 1987;Arcamone, 1987;Israel et al, 1987). In Japan, the presently-used anthracycline derivatives are doxorubicin, epirubicin, pirarubicin, aclarubicin and daunorubicin.…”

mentioning

confidence: 99%

Effects of anthracycline derivatives on hepatic neoplastic nodules of Lewis lung carcinoma and colon adenocarcinoma 26

Iigo¹,

Nishikata²,

Nakajima³

et al. 1991

Br J Cancer

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New antitumor antibiotics, aclacinomycins A and B.

Cited by 221 publications

References 5 publications

In vitro evaluation of the potential of aclarubicin in the treatment of small cell carcinoma of the lung (SCCL)

In vitro evaluation of the potential of aclarubicin in the treatment of small cell carcinoma of the lung (SCCL)

Differentiation Inducing Activity of Anthracycline Compounds in Friend Leukemia Cells

Effects of anthracycline derivatives on hepatic neoplastic nodules of Lewis lung carcinoma and colon adenocarcinoma 26

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