Ganoderma tsugae induced ROS-independent apoptosis and cytoprotective autophagy in human chronic myeloid leukemia cells.

The medicinal fungus Ganoderma, known in Chinese as Lingzhi or Reishi, traditionally has various medicinal uses and has been employed in cancer treatment in Asia for centuries. This study used ethanol-extracted Ganoderma tsugae (GT) and examined its antitumor activities on human chronic myeloid leukemia cells as well as its molecular mechanism of action. Treatment with GT (200-400 µg/mL) significantly reduced cell viability and caused G2/M arrest in K562 cells. In addition, GT induced mitochondrial and death receptor mediated apoptosis, correlated with DNA fragmentation, followed by cytochrome c release, caspase-3/8/9 activation, PARP cleavage, Fas activation, Bid cleavage, and Bax/Bcl-2 dysregulation. Cytoprotective autophagy was found to be induced by GT, as was revealed by increased LC3-II accumulation, Beclin-1/Bcl-2 dysregulation, acidic vesicular organelle formation, and p62/SQSTM1 activation. Notably, pretreatment of cells with the autophagy inhibitors 3-MA and CQ enhanced GT-induced apoptosis. Interestingly, reactive oxygen species production in cells was not triggered by GT administration; equally, the antioxidant N-acetylcysteine was found to be incapable of preventing apoptosis and autophagy induced by GT treatment. Finally, this study discovered that cytoprotective autophagy induced by GT was associated with EGFR and PI3K/AKT/mTOR signaling cascade suppression. In summary, GT demonstrated antitumor activity against human chronic myeloid leukemia.

Regulatory effects of fisetin on microglial activation.

Increasing evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play a key role in neurodegeneration. Fisetin, a plant flavonol commonly found in fruits and vegetables, is frequently added to nutritional supplements due to its antioxidant properties. In the present study, treatment with fisetin inhibited microglial cell migration and ROS (reactive oxygen species) production. Treatment with fisetin also effectively inhibited LPS plus IFN-γ-induced nitric oxide (NO) production, and inducible nitric oxide synthase (iNOS) expression in microglial cells. Furthermore, fisetin also reduced expressions of iNOS and NO by stimulation of peptidoglycan, the major component of the Gram-positive bacterium cell wall. Fisetin also inhibited the enhancement of LPS/IFN-γ- or peptidoglycan-induced inflammatory mediator IL (interlukin)-1 ß expression. Besides the antioxidative and anti-inflammatory effects of fisetin, our study also elucidates the manner in fisetin-induced an endogenous anti-oxidative enzyme HO (heme oxygenase)-1 expression. Moreover, the regulatory molecular mechanism of fisetin-induced HO-1 expression operates through the PI-3 kinase/AKT and p38 signaling pathways in microglia. Notably, fisetin also significantly attenuated inflammation-related microglial activation and coordination deficit in mice in vivo. These findings suggest that fisetin may be a candidate agent for the development of therapies for inflammation-related neurodegenerative diseases.

Tumor detection strategy using ZnO light-emitting nanoprobes.

Traditional methods of detecting cancer cells, such as fluorescence, have their limits and can hardly be used for identification during tumor resection. Here we report an alternative tumor detection technology using ZnO nanorods bonded to antibodies as cancer cell probes. Our experiment shows that antibodies toward epidermal growth factor receptor (EGFR) can be connected to ZnO nanorods and to EGFR receptors of SCC (squamous cell carcinoma). The cancer cell can be recognized by the naked eye or an optical microscope with the help of purple light emission from ZnO/EGFR antibody probes. On the other hand, for cells with less EGFR expression, in our case Hs68, no purple light was observed as the probes were washed off. From the photoluminescent spectra, the peak intensity ratio between the purple light (from ZnO at the wavelength 377 nm) and the green band (from the autofluorescence of cells) is much higher with the presence in SCC, as compared with Hs68. The ZnO/EGFR antibody probes have the potential to be applied to surgery for real-time tumor cell identification. The cancer cells will be excised with the help of purple light emission.

Induction of primitive pigment cell differentiation by visible light (helium-neon laser): a photoacceptor-specific response not replicable by UVB irradiation.

Solar lights encompass ultraviolet (UV), visible, and infrared spectrum. Most previous studies focused on the harmful UV effects, and the biologic effects of lights at other spectrums remained unclear. Recently, lights at visible region have been used for regenerative purposes. Using the process of vitiligo repigmentation as a research model, we focused on elucidating the pro-differentiation effects induced by visible light. We first showed that helium-neon (He-Ne) laser (632.8 nm) irradiation stimulated differentiation of primitive pigment cells, an effect not replicable by UVB treatment even at high and damaging doses. In addition, significant increases of mitochondrial DNA copy number and the regulatory genes for mitochondrial biogenesis were induced by He-Ne laser irradiation. Mechanistically, we demonstrated that He-Ne laser initiated mitochondrial retrograde signaling via a Ca(2+)-dependent cascade. The impact on cytochrome c oxidase within the mitochondria is responsible for the efficacy of He-Ne laser in promoting melanoblast differentiation. Taken together, we propose that visible lights from the sun provide important environmental cues for the relatively quiescent stem or primitive cells to differentiate. In addition, our results also indicate that visible light may be used for regenerative medical purposes involving stem cells.