Rebeccamycin, a yellow crystalline product, is isolated from the mycelium. It has activity against P388 leukemia, L1210 leukemia, and B16 melanoma implanted in mice. Rebeccamycin is also an antitumor antibiotic produced by the actinomycete Saccharotrix aerocolonigenes with activity against several human tumor cell lines, including A549 (lung adenocarcinoma), HCT-116 (colon carcinoma), and KB (nasopharyngeal carcinoma).

Topoisomerases I and II are enzymes that alter the topological state of DNA by generating transient breaks in the sugar-phosphate backbone of DNA, allowing DNA relaxation when needed for proper cellular function. Topoisomerase enzymes all possess three key functions: (a) the cleavage of DNA; (b) the passage of intact DNA through the cleaved strand; and (c) the religation of cleaved segments. Epipodophyllotoxins, such as etoposide, and camptothecins, such as irinotecan or topotecan, inhibit the third function, the religation of cleaved DNA by topoisomerases II and I, respectively.

Rebeccamycin, an antitumor antibiotic, inhibits DNA topoisomerase I.

In contrast to staurosporine, which has potent inhibitory effects on the protein kinases A, C, and K, rebeccamycin appears to exert its primary antineoplastic effect by poisoning topoisomerase I and has a negligible effect on protein kinase C and topoisomerase II. Rebeccamycin inhibits topoisomerase I in a manner comparable with the camptothecins. i.e., it stabilizes the topoisomerase-DNA covalent complex such that DNA may be cleaved but not resealed. However, in contrast to the camptothecins, which only bind to DNA in the presence of topoisomerase I, rebeccamycin and its analogs appear capable of intercalating DNA in the absence of topoisomerase I.


Rebeccamycin inhibits the growth of human lung adenocarcinoma cells (A549) and produces single-strand breaks in the DNA of these cells. Meanwhile, Rebeccamycin shows antibacterial activity against several Gram-positive bacteria, including Staphylococcus aureus and Streptococcus faecalis.

Rebeccamycin (2-256 mg/kg; i.p.; daily for 9 days) also prolongs survival in B16 melanoma, L1210 leukemia.

In conclusion, Rebeccamycin, a potent DNA Topoisomerase I inhibitor, has the potential for the research of cancer diseases.



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[2]. Sánchez C, et al. Chem Biol. 2002 Apr;9(4):519-31.