Antitumor Effects and Tumor-specificity of Guaiazulene-3-Carboxylate Derivatives Against Oral Squamous Cell Carcinoma In Vitro.

AIM: The aim of this study was to investigate the antitumor potential of guaiazulene-3-carboxylate derivatives against oral malignant cells. MATERIALS AND METHODS: Twelve guaiazulene-3-carboxylate derivatives were synthesized by introduction of either with alkyl group [1-5], alkoxy group [6, 7], hydroxyl group [8, 9] or primary amine [10-12] at the end of sidechains. Tumor-specificity (TS) was calculated by the ratio of mean 50% cytotoxic concentration (CC50) against 3 human oral mesenchymal cell lines to that against 4 human oral squamous cell carcinoma (OSCC) cell lines. Potency-selectivity expression (PSE) was calculated by dividing TS value by CC50value against OSCC cell lines. Cell cycle analysis was performed by cell sorter. RESULTS: [6, 7] showed the highest TS and PSE values, and induced the accumulation of both subG1 and G2/M cell populations in HSC-2 OSCC cells. Quantitative structure-activity relationship analysis demonstrated that their tumor-specificity was correlated with chemical descriptors that explain the 3D shape, electric state and ionization potential. CONCLUSION: Alkoxyl guaiazulene-3-carboxylates [6, 7] can be potential candidates of lead compound for developing novel anticancer drugs.

Opposite domination of cyclic and pseudocyclic electron flows in short-illuminated dark-adapted leaves of angiosperms and gymnosperms.

The present work was aimed to explain the recently reported higher O2-dependent electron flow capacity in gymnosperms than in angiosperms and to search for other differences in the electron transport processes by simultaneous characterization of the relative capacities of pseudocyclic (direct or Flavodiiron proteins (Flv)-mediated O2-reduction, Mehler(-like) reactions) and cyclic electron flows around photosystem I (CEF-PSI). To this end, a comparative multicomponent analysis was performed on the fluorescence decay curves of dark-adapted leaves after illumination with a 1-s saturating light pulse. In both gymnosperms and angiosperms, two or three exponential decay components were resolved: fast (t 1/21 ~ 170-260 ms), middle (~1.0-2.3 s), and slow (>4.2 s). The sensitivity of the decay parameters (amplitudes A1-3, halftimes t 1/2 1-3) to the alternative electron flows was assessed using Arabidopsis pgr5 and ndhM mutants, defective in CEF-PSI, Synechocystis sp. PCC 6803 Δflv1 mutant, defective in Flv-mediated O2-photoreduction, different O2 concentrations, and methyl viologen treatment. A1 reflected the part of electrons involved in linear and O2-photoreduction pathways after PSI. The middle component appeared in pgr5 (but not in ndhM), in gymnosperms under low O2, and in Δflv1, and reflected limitations at the PSI acceptor side. The slow component was sensitive to CEF-PSI. The comparison of decay parameters provided evidence that Flv mediate O2-photoreduction in gymnosperms, which explains their higher O2-dependent electron flow capacity. The concomitant quantification of relative electrons branching in O2-photoreduction and CEF-PSI pathways under the applied non-steady-state photosynthetic conditions reveals that CEF-PSI capacity significantly exceeds that of O2-photoreduction in angiosperms while the opposite occurs in gymnosperms.