Search Results (4)

Esculeoside A and tomatine are two major steroidal alkaloids in tomato fruit (Solanum lycopersicum) that exhibit anti-inflammatory, anticancer, and anti-hyperlipidemia activities. Tomatine contained in immature tomato fruit is converted to esculeoside A as the fruit matures. To develop new tomato varieties based on the content analysis of functional secondary metabolites, 184 mutant lines were generated from the original cultivar (S. lycopersicum cv. Micro-Tom) by radiation breeding. Ultra-performance liquid chromatography coupled with evaporative light scattering detector was used to identify the mutant lines with good traits by analyzing tomatine and esculeoside A content. Compared with the original cultivar, candidates for highly functional cultivars with high esculeoside A content were identified in the mature fruit of the mutant lines. The mutant lines with low and high tomatine content at an immature stage were selected as edible cultivars due to toxicity reduction and as a source of tomatine with various pharmacological activities, respectively. During the process of ripening from green to red tomatoes, the rate of conversion of tomatine to esculeoside A was high in the green tomatoes with a low tomatine content, whereas green tomatoes with a high tomatine content exhibited a low conversion rate. Using methanol extracts prepared from unripe and ripe fruits of the original cultivar and its mutant lines and two major compounds, we examined their cytotoxicity against FaDu human hypopharynx squamous carcinoma cells. Only tomatine exhibited cytotoxicity with an IC₅₀ value of 5.589 μM, whereas the other samples did not exhibit cytotoxicity. Therefore, radiation breeding represents a useful tool for developing new cultivars with high quality, and metabolite analysis is applicable for the rapid and objective selection of potential mutant lines. Full article

The Dendrobium species (Orchidaceae) has been cultivated as an ornamental plant as well as used in traditional medicines. In this study, the chemical profiles of Dendrobii Herba, used as herbal medicine, Dendrobium in two different species, their hybrid, and the gamma-irradiated mutant lines of the hybrid, were systematically investigated via ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QToF MS). Among the numerous peaks detected, 17 peaks were unambiguously identified. Gigantol (1), (1R,2R)-1,7-hydroxy-2,8-methoxy-2,3-dihydrophenanthrene-4(1H)-one (2), tristin (3), (−)-syringaresinol (4), lusianthridin (5), 2,7-dihydroxy-phenanthrene-1,4-dione (6), densiflorol B (7), denthyrsinin (8), moscatilin (9), lusianthridin dimer (10), batatasin III (11), ephemeranthol A (12), thunalbene (13), dehydroorchinol (14), dendrobine (15), shihunine (16), and 1,5,7-trimethoxy-2-phenanthrenol (17), were detected in Dendrobii Herba, while 1, 2, and 16 were detected in D. candidum, 1, 11, and 16 in D. nobile, and 1, 2, and 16 in the hybrid, D. nobile × candidum. The methanol extract taken of them was also examined for cytotoxicity against FaDu human hypopharynx squamous carcinoma cells, where Dendrobii Herba showed the greatest cytotoxicity. In the untargeted metabolite analysis of 436 mutant lines of the hybrid, using UPLC-QToF MS and cytotoxicity measurements combined with multivariate analysis, two tentative flavonoids (M1 and M2) were evaluated as key markers among the analyzed metabolites, contributing to the distinction between active and inactive mutant lines. Full article

The poor prognosis of head and neck squamous cell carcinoma (HNSCC) is partly due to the lack of reliable predictive markers. Connexin 43 (Cx43) protein and its cell-communication channels have been assigned tumor suppressor functions while the anti-apoptotic Bcl-2 (B-cell lymphoma-2) protein has been associated with negative prognostic significance in cancer. This study aimed to test the role of Cx43 protein on Bcl-2 expression, tumor progression and response to taxane-based treatment in HNSCC. Human papillomavirus (HPV) negative HNSCC cell lines were tested for paclitaxel sensitivity through measuring apoptosis induction, cell viability and changes in Cx43 and Bcl-2 levels using flow cytometry, cell viability assay, immunocytochemistry and western blot. Inhibition of Cx43 expression using siRNA increased Bcl-2 protein levels in SCC25 (tongue squamous cell carcinoma) cells, while forced Cx43 expression reduced Bcl-2 levels and supported paclitaxel cytotoxicity in FaDu (hypopharynx squamous cell carcinoma) cells. In vitro results were in line with protein expression and clinicopathological features tested in tissue microarray samples of HNSCC patients. Our data demonstrate that elevated Cx43 and reduced Bcl-2 levels may indicate HNSCC sensitivity to taxane-based treatments. On the contrary, silencing of the Cx43 gene GJA1 (gap junction protein alpha-1) can result in increased Bcl-2 expression and reduced paclitaxel efficiency. Clinical tumor-based analysis also confirmed the inverse correlation between Cx43 and Bcl-2 expression. Full article

Two new phenanthrenes, (1R,2R)-1,7-hydroxy-2,8-methoxy-2,3-dihydrophenanthrene-4(1H)-one (1) and 2,7-dihydroxy-phenanthrene-1,4-dione (2), were isolated from the ethyl acetate-soluble fraction of Dendrobii Herba, together with seven known phenanthrenes (3–9), two bibenzyls (10–12), and a lignan (13). Structures of 1 and 2 were elucidated by analyzing one-dimensional (1D) and two-dimensional (2D)-NMR and High-resolution electrospray ionization mass spectra (HR-ESI-MS) data. The absolute configuration of compound 1 was confirmed by the circular dichroism (CD) spectroscopic method. In cytotoxicity assay using FaDu human hypopharynx squamous carcinoma cell line, compounds 3–6, 8, 10, and 12 showed activities, with IC₅₀ values that ranged from 2.55 to 17.70 μM. Full article