Anticancer properties of 10-hydroxycamptothecin in a murine melanoma pulmonary metastasis model in vitro and in vivo

Lung cancer, including lung metastatic cancer, remains one of the most difficult types of cancer to treat. Therefore, the search for new agents for its treatment is very important. 10-Hydroxycamptothecin (HCPT) was proved to have ideal anticancer activity in curing series cancer cells. In this study, the anticancer effect of HCPT on melanoma lung metastasis cancer was investigated by several administration routes, and whether the effect may be attributed to the induction of tumor cells apoptosis was determined. MTT assay results showed that HCPT exhibited selective cytotoxic activity against B16-F10 cells in a concentration- and time-dependent manner. Hoechst 33258 staining and transmission electron microscopy showed typical apoptotic morphology such as condensed chromatin, irregular nuclei, and apoptotic body formation. Flow cytometry analysis indicated a growth on apoptotic cells and a cell-cycle arrest in S phase after treatment with HCPT. In vivo melanoma pulmonary metastases were inhibited by treatment with HCPT. A more significant inhibition was observed if HCPT was administered by aerosol inhalation than that given by i.v. or i.p. administration. Thus, HCPT exhibited potential anticancer activity against B16-F10 cells in vitro and in vivo. However, the possible mechanisms involved still need to be investigated to explain this behavior. (C) 2010 Elsevier Ltd. All rights reserved.