The conformation change of Bcl-2 is involved in arsenic trioxide-induced apoptosis and inhibition of proliferation in SGC7901 human gastric cancer cells

<p>Abstract</p> <p>Background</p> <p>Arsenic trioxide has been established as a first-line agent for treating acute promyelocytic leukemia. Experimental data suggest that arsenic trioxide also can have a potential use as chemotherapeutic agent for other malignancies. The precise mechanisms of action of arsenic trioxide have though not been elucidated. As the role of Bcl-2 in arsenic trioxide-mediated cell apoptosis and conformation change of Bcl-2 in response to arsenic trioxide treatment has not been studied. The aim of the present study was to determine whether conformation change of Bcl-2 is involved in the action of arsenic trioxide.</p> <p>Methods</p> <p>Human gastric cancer SGC7901 cells were exposed to different concentrations of arsenic trioxide. Proliferation was measured by using the Kit-8 cell counting assay. Analysis of nuclear morphology was observed by DAPI staining. The apoptosis rates of cells treated with arsenic trioxide were analyzed by flow cytometry using Annexin V-FITC staining. The conformation change of Bcl-2 and Bax activation were detected by immunostaining and Western blot analysis. Total expression of Bcl-2 and Bax were examined by Western blot analysis.</p> <p>Results</p> <p>Arsenic trioxide inhibited the growth of human gastric cancer SGC7901 cells and induced apoptosis. There were two Bcl-2 phenotypes coexisting in SGC7901 cells and the Bcl-2 cytoprotective phenotype could change into a cytodestructive phenotype following conformational change of Bcl-2, triggered by arsenic trioxide exposure. Bax activation might also be involved in arsenic trioxide-induced Bcl-2 conformational change. Arsenic trioxide did not change levels of total Bcl-2 expression, but up-regulated total Bax expression for the treatment time ranging from 3 to 24 hours.</p> <p>Conclusion</p> <p>Arsenic trioxide induces apoptosis through induction of Bcl-2 conformational change, Bax activation and up-regulation of total Bax expression rather than affecting total Bcl-2 expression in human gastric cancer SGC7901 cells. The conformational change of Bcl-2 may be a novel described mechanism of arsenic trioxide-induced apoptosis in cancer cells.</p

ELM of ELM-WD: An extremely low mass hot donor star discovered in LAMOST survey

The Extremely Low Mass White Dwarfs (ELM WDs) and pre-ELM WDs are helium core white dwarfs with mass $<\sim 0.3M_{\odot}$. They are formed in close binaries and have lost over half of their initial masses via Common Envelope (CE) ejection or stable Roche Lobe Over Flow (RLOF). Both evolution simulations and observations show that a lower mass limit for ELM WDs exists at $\approx0.14M_{\odot}$. Here we report the discovery of an extremely low mass ELM WD, ID70904216 in LAMOST survey, that may be lower than the ELM WD mass limit. Based on LAMOST and P200 spectroscopic observations, ID70904216 shows orbital period $P_{orb} =$ 0.219658 days and radial velocity semi-amplitude $K1=317.33km/s$, which gives the mass function of 0.73$M_{\odot}$, indicating the companion is a compact star. The low resolution spectra shows a F type star with $T_{\rm eff} \sim 7361K$ without emission features. The temperature is consistent with that derived from SED fitting($7440K$) and multi-color light curve solution($7400K$). The optical light curves, in ZTF g, r and i bands and Catalina V band, show ellipsoidal variability with amplitudes $\approx30\%$, suggesting that the visible companion is heavily tidal distorted. Combining with the distance from Gaia survey, the WD code modeling estimates that the mass of the visible star is $M1=0.08^{+0.06}_{-0.03}M_{\odot}$, and the mass of the invisible star is $M2=0.94^{+0.45}_{-0.10}M_{\odot}$. The radius of the visible donor is $R=0.29\pm0.01R_{\odot}$. The inclination angle is constrained between 60$^{\circ}$ and 90$^{\circ}$. The observations indicate the system is a pre-ELM WD + WD/NS binary system with an extremely low mass hot donor below the $0.14M_{\odot}$ theoretical limit.Comment: 16 pages, 10 figure

Orbital parameters for an ELM white dwarf with a white dwarf companion: LAMOST J033847.06+413424.2

Double white dwarf systems are of great astrophysical importance in the field of gravitational wave and Type Ia supernova. While the binary fraction of CO core white dwarf is about a few percents, the extremely low mass white dwarfs are all thought to be within binary systems. In this work, we report the orbital solution of a double degenerate system: J033847.06+413424.24, an extremely low mass He core white dwarf orbiting a CO core white dwarf. With LAMOST and P200, time domain spectroscopic observations have been made and spectral atmosphere parameters are estimated to be $T_{\rm eff}\sim22500$ K and log $g\sim5.6$ dex. Combining Gaia parallax, 3D extinction, and evolution tracks, we estimate a radius of $\sim0.12$ $R_{\odot}$ and a mass of $\sim0.22$ $M_{\odot}$. With the 37 single exposure spectra, the radial velocities are measured and the orbital parameters are estimated to be $P=0.1253132(1)$ days, $K1=289\pm4$ km/s and $V_{sys}=-41\pm3$ km/s. The radial velocity based system ephemeris is also provided. The light curves from several photometric surveys show no orbital modulation. The orbital solution suggests that the invisible companion has a minimum mass of about 0.60 $M_{\odot}$ and is $\sim0.79$ $M_{\odot}$ for an inclination of $60.0^{\circ}$, indicating most probably a CO core white dwarf. The system is expected to merge in about 1 Gyr. With present period and distance ($\sim596$ pc) it can not irradiate strong enough gravitational wave for LISA. More double degenerate systems are expected to be discovered and parameterized as the LAMOST survey goes on.Comment: 12 pages, 11 figure