Upregulation of tumor suppressor PIAS3 by Honokiol promotes tumor cell apoptosis via selective inhibition of STAT3 tyrosine 705 phosphorylation.

The natural product Honokiol exhibits robust antitumor activity against a range of cancers, and it has also received approval to undergo phase I clinical trial testing. We confrmed that honokiol can promote the apoptotic death of tumor cells through cell experiments. Then siRNA constructs specific for PIAS3, PIAS3 overexpression plasmid and the mutation of the STAT3 Tyr705 residue were used to confirm the mechanism of Honokiol-induced apoptosis. Finally, we confrmed that honokiol can promote PIAS3 upregulation, in turn suppressing STAT3 Tyr705 phosphorylation through the in vivo and in vitro experiments. Honokiol was ultimately found to reduce tumor cell viability by promoting apoptosis through a mechanism dependent on the ability of Honokiol to promote PIAS3 upregulation and the selective inhibition of p-STAT3 (Tyr705) without affecting p-STAT3 (Ser727) or p-STAT1 (Tyr701) levels. PIAS3 knockdown and overexpression in tumor cells altered STAT3 activation and associated DNA binding activity through the control of Tyr705 phosphorylation via PIAS3-STAT3 complex formation, ultimately shaping Honokiol-induced tumor cell apoptosis. Honokiol was also confirmed to significantly prolong the survival of mice bearing xenograft tumors in a PIAS3-dependent fashion. Together, these findings highlight a novel pathway through which Honokiol can promote PIAS3 upregulation, in turn suppressing STAT3 Tyr705 phosphorylation and promoting the apoptotic death of tumor cells.

Upconverting and persistent luminescent nanocarriers for accurately imaging-guided photothermal therapy.

The fluorescence-guided photothermal therapy (FPTT) has great potential in cancer treatment. However, the conventional FPTT has to be stimulated by external light, which tends to increase background noise and leads to the inaccurate infrared light irradiation for PTT. In this study, upconverting and persistent luminescent nanocarriers (UPLNs) loaded mesoporous silica nanoparticles (UPLNs@mSiO2) were first designed to solve the problem mentioned above. The UPLNs cores can effectively reduce the short-lived autofluorescence interference by exerting the delay time between signal acquisition and pulsed excitation light. For testing the luminescence properties, the indotcyanine green (ICG) as photothermal agent was encapsulated into the UPLNs@mSiO2. The experimental results showed that the UPLNs@mSiO2 nanoparticles could significantly reduce the short-lived autofluorescence interference and improve signal-to-noise ratio during FPTT. Our data suggest that UPLNs@mSiO2 may be a promising tool for improving the accuracy of PTT in vivo.

An efficient preparation of mulberroside a from the branch bark of mulberry and its effect on the inhibition of tyrosinase activity.

A bioactive ingredient in an ethanol extract from the branch bark of cultivated mulberry Husang-32 (Morus multicaulis Perr.) was isolated using a macroporous resin column. The primary component, which was purified by semi-preparative high-performance liquid chromatography diode array detection (HPLC-DAD), was identified as mulberroside A (MA) by liquid chromatograph-mass spectrometer (LC-MS), 1H and 13C nuclear magnetic resonance (NMR) spectra. In total, 4.12 g MA was efficiently extracted from one kilogram of mulberry bark. The enzymatic analysis showed that MA inhibited the generation of dopachrome by affecting the activities of monophenolase and diphenolase of tyrosinase in vitro. This analysis indicated that MA and oxyresveratrol (OR), which is the the aglycone of mulberroside A, exhibited strong inhibition of the monophenolase activity with IC50 values of 1.29 µmol/L and 0.12 µmol/L, respectively. However, the former showed weaker inhibitory activity than the latter for diphenolase. For the monophenolase activity, the inhibitory activity of MA and OR was reversible and showed mixed type 1 inhibition. Additionally, the inhibition constant KI (the inhibition constant of the effectors on tyrosinase) values were 0.385 µmol/L and 0.926 µmol/L, respectively, and the KIS (the inhibition constants of the enzyme-substrate complex) values were 0.177 µmol/L and 0.662 µmol/L, respectively. However, MA showed competitive inhibition of diphenolase activity, and KI was 4.36 µmol/L. In contrast, OR showed noncompetitive inhibition and KI = KIS = 2.95 µmol/L. Taken together, these results provide important information concerning the inhibitory mechanism of MA on melanin synthesis, which is widely used in whitening cosmetics.