RESUMEN
Objective: To study the chemical constituents from Orobanche cernua in Orobanchaceae. Methods: The chemical constituents were separated and purified by macroporous resin, silica gel, Sephadex LH-20, and MCI column chromatographies. Their structures were determined by physicochemical properties and spectral data. Results: Twelve compounds were isolated from 70% ethanol extract of O. cernua. Among them, eight phenylpropanoid glycosides were identified as acteoside (1), campneoside II (2), crenatoside (3), campneoside I (4), isocrenatoside (5), isoacteoside (6), leucosceptoside A (7), and cistanoside F (8), three liganans were identified as (+)-syringaresinol-4'-O-β-D-glucopyranoside (9), (+)-pinoresinol-4'-O-β-D-glucopyranoside (10), and isoeucommin A (11), and one steroide was stigmasterol-3-O-β-D-glucoside (12). Conclusion: Compounds 7 and 12 are isolated from the family Orobanchaceae for the first time; Compounds 4, 7, and 9-12 are isolated from the plants of Orobanche L. firstly, and compounds 2, 4, and 6-12 are found from O. cernua for the first time.
RESUMEN
Lack of immunogenicity of cancer cells has been considered a major reason for their failure in induction of a tumor specific T cell response. In this paper, we present evidence that decitabine (DAC), a DNA methylation inhibitor that is currently used for the treatment of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and other malignant neoplasms, is capable of eliciting an anti-tumor cytotoxic T lymphocyte (CTL) response in mouse EL4 tumor model. C57BL/6 mice with established EL4 tumors were treated with DAC (1.0 mg/kg body weight) once daily for 5 days. We found that DAC treatment resulted in infiltration of IFN-γ producing T lymphocytes into tumors and caused tumor rejection. Depletion of CD8(+), but not CD4(+) T cells resumed tumor growth. DAC-induced CTL response appeared to be elicited by the induction of CD80 expression on tumor cells. Epigenetic evidence suggests that DAC induces CD80 expression in EL4 cells via demethylation of CpG dinucleotide sites in the promoter of CD80 gene. In addition, we also showed that a transient, low-dose DAC treatment can induce CD80 gene expression in a variety of human cancer cells. This study provides the first evidence that epigenetic modulation can induce the expression of a major T cell co-stimulatory molecule on cancer cells, which can overcome immune tolerance, and induce an efficient anti-tumor CTL response. The results have important implications in designing DAC-based cancer immunotherapy.