inotodiol and Adenocarcinoma

To observe the proliferation inhibition, apoptosis, and cell proliferation cycle of human lung carcinoma cell line A549 treated with Inotodiol extracts from Inonotus obliquus and explore the possibility of Inotodiol extracts from Inonotus obliquus as a new tumor chemopreventive drug.. Human lung cancer cell line A549 was treated with different concentrations of Inotodiol, the effects of Inotodiol on cell apoptosis, the expression of Ki-67, Bcl-2, Bax, and p53 and cell cycle were detected by TUNEL assay, immunohistochemistry, and flow cytometry assay respectively.. Inotodiol extracts had antiproliferation effect on human lung carcinoma cell line A549. The expression of Ki-67 decreased with the increase of Inotodiol concentration and exposure time (P<0.05), in a dose-dependent and time-dependent manner. The typical characteristics of the apoptosis of A549 cells treated with Inotodiol were observed, and the apoptotic rate of A549 cell at 48 h was the highest by TUNEL assay. Inotodiol arrested A549 cells in the S phase, and apoptotic peak was observed by flow cytometry. Immunocytochemistry indicated that the expression of Bcl-2 protein decreased, while the expression of p53 and Bax proteins increased in A549 cells treated with Inotodiol, compared with the control cells (P<0.05).. Inotodiol can inhibit proliferation and induce the apoptosis of A549 cells, and its molecular mechanism may be associated with the up-regulating expression of p53 and bax proteins and down-regulating expression of Bcl-2 protein, which arrested A549 cells in S phase.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Apoptosis; Basidiomycota; bcl-2-Associated X Protein; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Drug Evaluation, Preclinical; Drugs, Chinese Herbal; Gene Expression Regulation, Neoplastic; Genes, bcl-2; Genes, p53; Humans; Ki-67 Antigen; Lanosterol; Lung Neoplasms; Phytotherapy

Two new lanostane-type triterpenoids, inonotsuoxides A (1) and B (2) along with three known lanostane-type triterpenoids, inotodiol (3), trametenolic acid (4), and lanosterol (5), were isolated from the sclerotia of Inonotus obliquus (Pers.: Fr.) (Japanese name: Kabanoanakake) (Russian name: Chaga). Their structures were determined to be 22R,25-epoxylanost-8-ene-3beta,24S-diol (1) and 22S,25-epoxylanost-8-ene-3beta,24S-diol (2) on the basis of spectral data including single crystal X-ray analysis. These compounds except for 2 were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), as a test for potential cancer chemopreventive agents. The most abundant triterpene, inotodiol (3), was investigated for the inhibitory effect in a two-stage carcinogenesis test on mouse skin using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. Compound 3 was found to exhibit the potent anti-tumor promoting activity in the in vivo carcinogenesis test.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Adenocarcinoma; Animals; Antigens, Viral; Antineoplastic Agents; Basidiomycota; Cell Line, Tumor; Crystallography, X-Ray; Drug Screening Assays, Antitumor; Female; Lanosterol; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred ICR; Models, Molecular; Molecular Conformation; Plant Extracts; Reference Standards; Stereoisomerism; Structure-Activity Relationship; Tetradecanoylphorbol Acetate; Triterpenes; Xenograft Model Antitumor Assays