Peroxiredoxin 5 protects HepG2 cells from ethyl ß-carboline-3-carboxylate-induced cell death via ROS-dependent MAPK signalling pathways.

Peroxiredoxin 5 (PRDX5) is the member of Prxs family, widely reported to be involved in various types of cell death. We previously found that PRDX5 knockdown increases the susceptibility of cell death upon oxidative stress treatment. Ethyl ß-carboline-3-carboxylate (ß-CCE), an alkaloid extracted from Picrasma quassioides, has been reported to play a role in neuronal disease, but its anti-cancer potential on liver cancers remains unknown. Here, we studied the effect of PRDX5 on ethyl ß-carboline-3-carboxylate (ß-CCE)-induced apoptosis of hepatomas. High expression level of PRDX5 was deeply related with the postoperative survival of patients with liver cancer, indicating that PRDX5 may be a biomarker of live cancer processing. Moreover, PRDX5 over-expression in HepG2 cells significantly inhibited ß-CCE-induced cell apoptosis and cellular ROS levels as well as mitochondrial dysfunction. Signalling pathway analysis showed that ß-CCE could significantly up-regulate the ROS-dependent MAPK signalling, which were in turn boosts the mitochondria-dependent cell apoptosis. Moreover, PRDX5 over-expression could reverse the anti-cancer effects induced by ß-CCE in HepG2 cells. Our findings suggest that PRDX5 has a protective role on ß-CCE-induced liver cancer cell death and provides new insights for using its anti-cancer properties for liver cancer treatment.

Pharmacological effects of Picrasma quassioides (D. Don) Benn for inflammation, cancer and neuroprotection (Review).

Picrasma quassioides (D. Don) Benn is an Asian shrub with a considerable history of traditional medicinal use. P. quassioides and its extracts exhibit good therapeutic properties against several diseases, including anti-inflammatory, antibacterial and anticancer effects. However, the composition of compounds contained in P. quassioides is complex; although various studies have examined mixtures or individual compounds extracted from it, studies on the application of P. quassioides extracts remain limited. In the present review, the structures and functions of the compounds identified from P. quassioides and their utility in anti-inflammatory, anticancer and neuroprotectant therapies was discussed. The present review provided up-to-date information on pharmacological activities and clinical applications for P. quassioides extracts.

Anticancer Effect of ERM210 on Liver Cancer Cells Through ROS/Mitochondria-dependent Apoptosis Signaling Pathways.

BACKGROUND/AIM: Asian Traditional medicines are renowned for their antitumor properties and are efficacious in the clinical treatment of various cancer types. ERM210 is a Korean traditional medicine comprising nine types of medicinal plants. In the present study, we examined the pro-apoptotic effect and molecular mechanisms of the effects of ERM210 on HepG2 liver cancer cells. MATERIALS AND METHODS: The cytotoxicity of ERM210 on HepG2 cells was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and wound-healing assays, and apoptosis and signaling pathways by fluorescence microscopy flow cytometry and western blotting. RESULTS: ERM210 significantly impaired HepG2 cell viability and enhanced mitochondria-dependent cellular apoptosis in a time- and dose-dependent manner by up-regulating the expression of caspases 3, 7 and 9, and of BCL2 apoptosis regulator (BCL2)-associated X, apoptosis regulator (BAX) proteins, whilst down-regulating that of BCL2 protein. Furthermore, ERM210 treatment increased accumulation of cellular and mitochondrial reactive oxygen species (ROS) and significantly inhibited cell migration. Additionally, all these phenomena were reversed by treating with the ROS scavenger N-acetylcysteine. The analysis of signaling proteins revealed that ERM210 significantly up-regulated the phosphorylation of ROS-dependent mitogen-activated protein kinases (p38, extracellular-regulated kinase, and c-Jun N-terminal kinase in HepG2 liver cancer cells. CONCLUSION: ERM210 exerts anticancer effects in HepG2 liver cancer cells by up-regulating ROS/mitochondria-dependent apoptosis signaling, providing new insight into the possibility of employing this traditional medicine for the clinical treatment of liver cancer.

BRM270 targets cancer stem cells and augments chemo-sensitivity in cancer.

Over the past decade, a number of studies have demonstrated the resistance of cancer cells to conventional drugs and have recognized this as a major challenge in cancer therapy. While attempting to understand the underlying mechanisms of chemoresistance, several studies have suggested that the presence of cancer stem cells (CSCs) in tumors is one of the major pathways contributing toward resistance. Chemoresistance leads to cancer treatment failure and worsens the prognosis of patients. Natural herbal compounds are gaining attention as an alternative treatment strategy for cancer. These compounds may be effective against chemoresistant cells either alone or synergistically alongside conventional drugs, sensitizing cancer cells and enhancing the therapeutic efficacy. BRM270 is a natural compound made from seven herbal plant (Saururus chinensis, Citrus unshiu Markovich, Aloe vera, Arnebia euchroma, Portulaca oleracea, Prunella vulgaris var. lilacina and Scutellaria bacicalensis) extracts used in Asian traditional medicine and has the potential to target CSCs. Several studies have demonstrated the positive effects of BRM270 against chemoresistant cancer and its synergy alongside existing cancer drugs, including paclitaxel and gefitinib. These effects have been observed against various cancer types, including resistant non-small cell lung cancer (NSCLC), glioblastoma, multi-drug resistant osteosarcoma, cervical cancer, pancreatic cancer and hepatocarcinoma. The present review discusses the effects of BRM270 treatment against CSC-associated chemoresistance in common types of cancer.

Picrasma quassioides Extract Elevates the Cervical Cancer Cell Apoptosis Through ROS-Mitochondrial Axis Activated p38 MAPK Signaling Pathway.

BACKGROUND/AIM: Picrasma quassioides (P. quassioides) is used in traditional Asian medicine widely for the treatment of anemopyretic cold, eczema, nausea, loss of appetite, diabetes mellitus, hypertension etc. In this study we aimed to understand the effect of P. quassioides ethanol extract on SiHa cervical cancer cell apoptosis. MATERIALS AND METHODS: The P. quassioides extract-induced apoptosis was analyzed using the MTT assay, fluorescence microscopy, flow cytometry and western blotting. RESULTS: P. quassioides extract induced cellular apoptosis by increasing the accumulation of cellular and mitochondrial reactive oxygen species (ROS) levels and inhibiting ATP synthesis. Pretreatment with N-Acetylcysteine (NAC), a classic antioxidant, decreased the intracellular ROS production and inhibited apoptosis. In addition, the P38 MAPK signaling pathway is a key in the apoptosis of SiHa cells induced by the P. quassioides extract. CONCLUSION: The P. quassioides extract exerts its anti-cancer properties on SiHa cells through ROS-mitochondria axis and P38 MAPK signaling. Our data provide a new insight for P. quassioides as a therapeutic strategy for cervical cancer treatment.

Anti-tumor Properties of Picrasma quassioides Extracts in H-RasG12V Liver Cancer Are Mediated Through ROS-dependent Mitochondrial Dysfunction.

BACKGROUND: Picrasma quassioides (PQ) is a traditional Asian herbal medicine with anti-tumor properties that can inhibit the viability of HepG2 liver cancer cells. H-Ras is often mutated in liver cancer, however, the effect of PQ treatment on H-Ras mutated liver cancer is unclear. This study aimed to investigate the role of PQ on ROS accumulation and mitochondrial dysfunction in H-ras mutated HepG2 (HepG2G12V) cells. MATERIALS AND METHODS: PQ ethanol extract-induced HepG2G12V apoptosis was analyzed by the MTT assay, fluorescence microscopy, flow cytometry and western blotting. RESULTS: PQ treatment affected cell migration and colony formation in HepG2G12V cells. Cleaved-caspase-3, cleaved-caspase-9 and BCL2 associated agonist of cell death (BAD) expression levels were increased, while the levels of B-cell lymphoma-extra large (Bcl-xL) were decreased with PQ treatment. PQ treatment led to a reduction of H-Ras expression levels in liver cancer cells, thus reducing their abnormal proliferation. Furthermore, it led to increased expression levels of Peroxiredoxin VI, which regulates the redox signal in cells. CONCLUSION: Taken together these results provide a new functional significance for the role of PQ in treating HepG2G12V liver cancer.

Pump-induced dynamical tunneling in a deformed microcavity laser.

Pump-induced dynamical tunneling has been observed in free-space resonant optical pumping of a deformed microcavity by employing excitation spectroscopy. A focused-pump beam was injected into the cavity by refraction and then coupled to a high-Q cavity mode via dynamical tunneling. Pump-coupling efficiency as high as 50% and an effective coupling constant responsible for the tunneling were obtained from the observed pumping efficiency with a mode-mode coupling model.

Continuous control of the coupling constant in an atom-cavity system by using elliptic polarization and magnetic sublevels.

Atom-cavity coupling constant is a key parameter in cavity quantum electrodynamics for describing the interaction between an atom and a quantized electromagnetic field in a cavity. This paper reports a novel way to tune the coupling constant continuously by inducing an averaging of the atomic dipole moment over degenerate magnetic sublevels with elliptic polarization of the cavity field. We present an analytic solution of the stationary-state density matrix for this system with consideration of F -> F +1 hyperfine transition under a weak excitation condition. We rigorously show that the stationary-state emission spectra of this system can be approximated by that of a non-degenerate two-level atom with an effective coupling constant as a function of the elliptic angle of the cavity field only. A precise condition for this approximation is derived and its physical meaning is interpreted in terms of a population-averaged transition strength and its variance. Our results can be used to control the coupling constant in cavity quantum electrodynamics experiments with a degenerate two-level atom with magnetic sublevels. Possible applications of our results are discussed.

Quasieigenstate coalescence in an atom-cavity quantum composite.

We report the first direct observation of an exceptional point (EP) in an open quantum composite of a single atom and a high-Q cavity mode. The atom-cavity coupling constant was made a continuous variable by utilizing the multisublevel nature of a single rubidium atom when it is optimally coupled to the cavity mode. The spectroscopic properties of quasieigenstates of the atom-cavity composite were experimentally investigated near the EP. Branch-point singularity of quasieigenenergies was observed and its 4pi symmetry was demonstrated. Consequently, the cavity transmission at the quasieigenstate was observed to exhibit a critical behavior at the EP.

Rigorous criterion for characterizing correlated multiphoton emissions.

Strong correlation of photons, particularly in the single-photon regime, has recently been exploited for various applications in quantum information processing. Existing correlation measurements, however, do not fully characterize multi-photon correlation in a relevant context and may pose limitations in practical situations. We propose a conceptually rigorous, but easy-to-implement, criterion for detecting correlated multi-photon emission out of a quantum optical system, drawn from the context of wavefunction collapse. We illustrate the robustness of our approach against experimental limitations by considering an anharmonic optical system.

Observation of an exceptional point in a chaotic optical microcavity.

We present spectroscopic observation of an exceptional point or the transition point between mode crossing and avoided mode crossing of neighboring quasieigenmodes in a chaotic optical microcavity of a large size parameter. The transition to the avoided mode crossing was impeded until the degree of deformation exceeded a threshold deformation owing to the system's openness also enhanced by the shape deformation. As a result, a singular topology was observed around the exceptional point on the eigenfrequency surfaces, resulting in fundamental inconsistency in mode labeling.

Atomic Solc filter: multi-resonant photoemission via periodic poling of atom-cavity coupling constant.

This paper describes a novel atom-cavity interaction induced by periodically poled atom-cavity coupling constant which leads to multiple narrow photoemission bands for an initially inverted two-level atom under the strong coupling condition. The emission bandpass narrowing has a close analogy with the folded Solc filter in the context of quasi-phase matching by periodic poling. We present a closed form solution of the emission probability at the end of interaction and deduce the multiple phase matching condition for this system which is programmable by the interaction time. The Bloch sphere analysis provides a clear understanding of the underlying atomic dynamics associated with the multiple resonances in the semiclassical limit. Furthermore, we show that this interaction can be applied to generation of nonclassical fields with sub-Poisson photon statistics.

Nondestructive high-resolution soft-boundary profiling based on forward shadow diffraction.

Nondestructive noncontact high-resolution optical technique for profiling soft or fluidic boundary of an opaque object is presented. Our technique utilizes the fact that the angle width, the angular separation between two adjacent intensity minima in the forward shadow diffraction, is inversely proportional to the projected width of the object in the same direction. An analytic formula for reconstructing the boundary shape is obtained for an object with two-fold symmetry in terms of the angle widths measured for various rotational angles of the object. The typical error in determining the object shape parameter is less than 0.2%, which corresponds to 20 nm of radial accuracy when applied to an object with a mean radius of 10 microns.

Uncertainty-limited turnstile transport in deformed microcavities.

We present both experimental and theoretical evidence for uncertainty-limited turnstile transport in deformed microcavities. As the degree of cavity deformation was increased, a secondary peak gradually emerged in the far-field emission patterns to form a double-peak structure. Our observation can be explained in terms of the interplay between turnstile transport and its suppression by the quantum mechanical uncertainty principle.

Observation of a high Raman gain induced by a pulsed pump laser in a Lambda system of three fine-structure levels.

We have observed a high Raman gain in a quasi-stationary state realized by a single strong-pulsed-pump laser. The Raman gain, originating from the population inversion in the dressed state picture, was as large as 1700% in a Lambda system of three fine-structure levels of atomic samarium, corresponding to a gain cross section comparable with the linear absorption cross section for the same transition.

Dependence of transverse and longitudinal resolutions on incident Gaussian beam widths in the illumination part of optical scanning microscopy.

We studied both theoretically and experimentally the intensity distribution of a Gaussian laser beam when it was focused by an objective lens with its numerical aperture up to 0.95. Approximate formulas for full width at half-maximum (FWHM) of the intensity distribution at focus were derived for very large and very small initial beam waists with respect to the entrance pupil radius of the objective lens. In experiments, the energy flux through a 0.5 microm pinhole was measured for various pinhole positions. It was found in theoretical analysis and confirmed in experiments that the FWHMs at focus in the transverse and longitudinal directions do not increase much from the ultimate FWHMs until the input beam waist is reduced below half of the entrance pupil radius.

Spectral line-shape measurement of an extremely weak amplitude-fluctuating light source by photon-counting-based second-order correlation spectroscopy.

We demonstrate line-shape measurement of an extremely weak amplitude-fluctuating light source by using photon-counting-based second-order correlation spectroscopy combined with the heterodyne technique. The amplitude fluctuation of a finite bandwidth introduces a low-lying spectral structure in the line shape, and thus its effect can be isolated from that of the phase fluctuation. Our technique provides extreme sensitivity suited for single-atom-level applications.

Observation of sub-poisson photon statistics in the cavity-QED microlaser.

We have measured the second-order correlation function of the cavity-QED microlaser output and observed a transition from photon bunching to antibunching with increasing average number of intracavity atoms. The observed correlation times and the transition from super- to sub-Poisson photon statistics can be well described by gain-loss feedback or enhanced-reduced restoring action against fluctuations in photon number in the context of a quantum microlaser theory and a photon rate equation picture. However, the theory predicts a degree of antibunching several times larger than that observed, which may indicate the inadequacy of its treatment of atomic velocity distributions.

Protective effect of T-type calcium channel blocker flunarizine on cisplatin-induced death of auditory cells.

Changes in intracellular Ca2+ level are involved in a number of intracellular events, including triggering of apoptosis. The role of intracellular calcium mobilization in cisplatin-induced hair cell death, however, is still unknown. In this study, the effect of calcium channel blocker flunarizine (Sibelium), which is used to prescribe for vertigo and tinnitus, on cisplatin-induced hair cell death was investigated in a cochlear organ of Corti-derived cell line, HEI-OC1, and the neonatal (P2) rat organ of Corti explant. Cisplatin induced apoptotic cell death showing nuclear fragmentation, DNA ladder, and TUNEL positive in both HEI-OC1 and primary organ of Corti explant. Flunarizine significantly inhibited the cisplatin-induced apoptosis. Unexpectedly, flunarizine increased the intracellular calcium ([Ca2+]i) levels of HEI-OC1. However, the protective effect of flunarizine against cisplatin was not mediated by modulation of intracellular calcium level. Treatment of cisplatin resulted in ROS generation and lipid peroxidation in HEI-OC1. Flunarizine did not attenuate ROS production but inhibited lipid peroxidation and mitochondrial permeability transition in cisplatin-treated cells. This result suggests that the protective mechanism of flunarizine on cisplatin-induced cytotoxicity is associated with direct inhibition of lipid peroxidation and mitochondrial permeability transition.

Observation of scarred modes in asymmetrically deformed microcylinder lasers.

We report observation of lasing in the scarred modes in an asymmetrically deformed microcavity made of liquid jet. The observed scarred modes correspond to morphology-dependent resonance of radial mode order 3 with their Q values in the range of 10(6). Emission directionality is also observed, corresponding to a hexagonal unstable periodic orbit.