Topoisomerase I Inactivation by Reticulol and Its in vivo Cytotoxicity against B16F10 Melanoma

Abstract

To investigate the enzyme-inhibitory efficacy and the cytotoxicity of reticulol produced from a strain of Streptoverticillium, we conducted a DNA topoisomerase (Topo) cleavage assay and an in vivo assay using B16F10 melanoma. From the inhibition assay of reticulol for Topo I, which is involved in melanoma metastasis, it was seen that Topo I treated with 45 µM reticulol did not replicate or transcribe DNA by forming supercoiled DNA. In the annexin V/propidium iodide staining assay to investigate the death pattern of B16F10 cells treated with 200 µM reticulol, proliferation of B16F10 cells was inhibited due to necrosis. Furthermore, from the in vivo assay, reticulol combined with Adriamycin (a mixture with retinolol 5 mg/kg and Adriamycin 1 mg/kg) further retarded the tumor growth compared to that in mice treated with Adriamycin alone (1 mg/kg). The survival rate of tumor-bearing mice treated with the mixture was closely associated with its cytotoxicity. Taken together, these results suggested that reticulol inactivates Topo I, which is involved in tumor metastasis, and exhibits excellent cytotoxic efficacy against B16F10 melanoma, when combined with Adriamycin, in a mouse model.

2,3-Dehydrosilybin Is a Better DNA Topoisomerase I Inhibitor than Its Parental Silybin

“…In line with this argument, flavanonal silybin exhibited much weaker topo I inhibitors than flavonolignan DHS, and this correlates with a lack of ⌬ ⌿ m loss and DNA%SubG1 induction by silybin. Our results showed that DHS caused inhibition of topo I activity in both extractable and purified topo I at approximately 20-30 M , which are consistent with those reported for other topo I inhibitors [25] .…”

Regioselective Synthesis of Isochromenones by Iron(III)/PhSeSePh-Mediated Cyclization of 2-Alkynylaryl Esters

“…Some chromenone derivatives have proven to be antimicrobial, anticancer, antioxidant and anti-inflammatory, anti-HIV, and anticoagulant agents. Typical examples include reticulol (Scheme ), described as a potent inhibitor of cyclic nucleotide phosphodiesterase, a topoisomerase I inactivator and an inhibitior of lung metastasis . In addition, capillarin (Scheme ), which contains a propargyl group at the 3-position of the heterocyclic ring, shows a potent antifungal activity .…”