Antitumor activity of siwenmycin: a novel anthracycline antibiotic.
A novel anthracycline antibiotic, siwenmycin, isolated from the culture of Streptomyces galilaeus var. siwenesis, was examined for its antitumor activities against P388, K562, B16-F10, HeLa, HEp-2 and Lewis lung carcinoma cell lines. The results showed that siwenmycin was effective against P388, K562, HeLa and HEp-2 tumor cell lines in vitro, and significantly inhibited the growth of the Lewis lung carcinoma cell line in vivo. Siwenmycin could also suppress spontaneous and artificial pulmonary metastases of B16-F10 and Lewis lung carcinoma cell lines in C57BL/6 mice. The inhibitory effect of siwenmycin on spontaneous pulmonary metastasis of Lewis lung carcinoma in C57BL/6 mice was even stronger than that of adriamycin (ADM), which is, at present, commonly used in clinical practice. Furthermore, the double-labeling test used in this study has verified that siwenmycin can inhibit cellular RNA synthesis at about one tenth the concentration required to inhibit DNA synthesis to the same degree, indicating that the antitumor mechanism of siwenmycin also differs from that of ADM. The acute toxicity of siwenmycin was very low, and it was as effective in vivo as in vitro, suggesting that this newly found antibiotic should be studied for possible clinical antitumor applications.
Shen
W
W
Pharmacological Division, Sichuan Industrial Institute of Antibiotics, Chengdu, China.
Chen
R
R
Zhou
M
M
Chen
Y
Y
Hu
Q
Q
Wang
H
H
Wang
Y
Y
Jiao
H
H
D015250:Aclarubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007274:Injections, Intraperitoneal; D008175:Lung Neoplasms / Q000188:drug therapy; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008815:Mice, Inbred Strains; D008936:Mitolactol / Q000008:administration & dosage / Q000494:pharmacology; D008937:Mitomycins / Q000008:administration & dosage / Q000494:pharmacology; D009362:Neoplasm Metastasis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; D008937:Mitomycins; D012334:RNA, Neoplasm; C011157:aclacinomycins; D015250:Aclarubicin; D004317:Doxorubicin; D008936:Mitolactol