Anti-CDK2 monoclonal antibody, clone 3C7 + 9E5

Fourteen derivatives of the marine-derived fradcarbazole A were synthesized from staurosporine. Their structures were identified by NMR and high-resolution electrospray ionization mass spectrometry (HRESIMS). The derivatives were screened in vitro for antiproliferative activity against three human leukemic cell lines (MV4-11, HL-60, K562). All of the derivatives displayed cytotoxicity against the human FLT-3 internal tandem duplication (ITD) mutant acute myeloid leukemia (AML) cell line MV4-11 with IC50 values of 0.32-0.96 mu M. The mechanism of action studies indicated that the most effective 3-chloro-5(2) '-fluorofradcarbazole A (6) induced apoptosis of the MV4-11 cells and arrested the cell cycle at the G(0)/G(1) phase. Furthermore, compound 6 can reduce the expression of FLT-3, CDK2, and c-kit. The results suggest that 3-chloro-5 '''-fluorofradcarbazole A (6) is a potential candidate for developing novel anti-AML agents in the future.

Cathepsin L (CTSL) is a lysosomal acid cysteine protease that has been implicated in tumorigenesis and malignant progression. In the present study, the role of CTSL in tumorigenesis and prognosis of breast cancer was evaluated. The prognostic value of CTSL was analyzed using immunohistochemistry in patients with breast cancer, as well as online microarray datasets. CTSL expression was knocked down in the breast cancer cell line T-47D using RNA interference. MTT and colony formation assays were performed to assess the role of CTSL in the proliferation of breast cancer cells. Cell cycle progression and apoptosis were measured using flow cytometry. A physical interaction of CTSL and cyclin dependent kinase 2 associated protein 1 (CDK2-AP1) was determined using a glutathione S-transferase pull-down assay. Endogenous CTSL expression was high in breast cancer cells and exhibited an inverse association with CDK2-AP1 expression; aberrant expression of CTSL in breast cancer tissues predicted an improved clinical outcome and prognosis. In addition, CTSL knockdown decelerated the progression of breast cancer cells by arresting cell cycle progression and increasing apoptosis. Thus, CTSL may be a potential therapeutic target for treating patients with breast cancer.