No abstract

Resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis has been reported in some cancer cells, including AGS human gastric adenocarcinoma cells. Hizikia fusiforme is a commonly used brown seaweed species in Korea that possesses potent antibacterial, antifungal, and anti-inflammatory activities. In this study, we demonstrated that treatment with TRAIL in combination with subtoxic concentrations of ethyl alcohol extract of H. fusiforme (EAHF) sensitized TRAIL-resistant AGS cells to TRAIL-mediated apoptosis. Combined treatment with EAHF and TRAIL increased chromatin condensation, DNA fragmentation, and sub-G1-phase DNA content. The restored sensitivity to TRAIL-induced apoptosis appeared to be correlated with the modulation of Bcl-2 family proteins and activation of caspases, which resulted in the cleavage of poly(ADP-ribose)polymerase. Taken together, the use of EAHF in combination with TRAIL may be an effective and selective anticancer strategy via suppressing the resistance to TRAIL-induced apoptosis in some tumor cell lines, including AGS cells.

The biochemical mechanisms of cell death by oleifolioside B (OB), a cycloartane-type triterpene glycoside isolated from Dendropanax morbifera Leveille, were investigated in A549 human lung carcinoma cells. Our data indicated that exposure to OB led to caspase activation and typical features of apoptosis; however, apoptotic cell death was not prevented by z-VAD-fmk, a pan-caspase inhibitor, demonstrating that OB-induced apoptosis was independent of caspase activation. Subsequently, we found that OB increased autophagy, as indicated by an increase in monodansylcadaverine fluorescent dye-labeled autophagosome formation and in the levels of the autophagic form of microtubule-associated protein 1 light chain 3 and Atg3, an autophagy-specific gene, which is associated with inhibiting phospho-nuclear factor erythroid 2-related factor 2 (Nrf2) expression. However, pretreatment with bafilomycin A1, an autophagy inhibitor, attenuated OB-induced apoptosis and dephosphorylation of Nrf2. The data suggest that OB-induced autophagy functions as a death mechanism in A549 cells and OB has potential as a novel anticancer agent capable of targeting apoptotic and autophagic cell death and the Nrf2 signaling pathway.

Background: (Z)-Stellettic acid C, an acetylenic acid from the marine sponge Stelletta sp., has been shown to have cytotoxic activity in some cancer cells; however, its mechanisms on malignant cell growth are not known. In this study, the potential of (Z)-stellettic acid C to induce apoptosis in human leukemic U937 cells and its effects on telomerase activity were investigated. Methods: Cytotoxicity was evaluated by MTT assays. Apoptosis was detected using DAPI staining and annexin V fluorescein. The mRNAs of Bcl-2, inhibitor of apoptosis proteins (IAPs) family and Fas/FasL system were determined by RT-PCR. Caspases and telomerase activities were measured using colorimetric assay and telomeric repeat amplification protocol enzyme-linked immunosorbent assay (TRAP-ELISA), respectively. Results: Exposure of U937 cells to (Z)-stellettic acid C resulted in growth inhibition and induction of apoptosis in a dose-dependent manner, which was associated with the modulation of Bcl-2 family expression, activation of caspases and downregulation of IAPs family members. (Z)-Stellettic acid C treatment markedly inhibited the activity of telomerase in a dose-dependent fashion. Additionally, the expression of human telomerase reverse transcriptase, a main determinant of the telomerase enzymatic activity, was progressively downregulated by (Z)-stellettic acid C treatment. Conclusions: These results suggest that (Z)-stellettic acid C could have a possible cancer therapeutic potential.