HIV Protease Inhibitors Sensitize Human Head and Neck Squamous Carcinoma Cells to Radiation by Activating Endoplasmic Reticulum Stress

Background Human head and neck squamous cell carcinoma (HNSCC) is the sixth most malignant cancer worldwide. Despite significant advances in the delivery of treatment and surgical reconstruction, there is no significant improvement of mortality rates for this disease in the past decades. Radiotherapy is the core component of the clinical combinational therapies for HNSCC. However, the tumor cells have a tendency to develop radiation resistance, which is a major barrier to effective treatment. HIV protease inhibitors (HIV PIs) have been reported with radiosensitizing activities in HNSCC cells, but the underlying cellular/molecular mechanisms remain unclear. Our previous study has shown that HIV PIs induce cell apoptosis via activation of endoplasmic reticulum (ER) stress. The aim of this study was to examine the role of ER stress in HIV PI-induced radiosensitivity in human HNSCC. Methodology and Principal Findings HNSCC cell lines, SQ20B and FaDu, and the most commonly used HIV PIs, lopinavir and ritonavir (L/R), were used in this study. Clonogenic assay was used to assess the radiosensitivity. Cell viability, apoptosis and cell cycle were analyzed using Cellometer Vision CBA. The mRNA and protein levels of ER stress-related genes (eIF2α, CHOP, ATF-4, and XBP-1), as well as cell cycle related protein, cyclin D1, were detected by real time RT-PCR and Western blot analysis, respectively. The results demonstrated that L/R dose-dependently sensitized HNSCC cells to irradiation and inhibited cell growth. L/R-induced activation of ER stress was correlated to down-regulation of cyclin D1 expression and cell cycle arrest under G0/G1 phase. Conclusion and Significance HIV PIs sensitize HNSCC cells to radiotherapy by activation of ER stress and induction of cell cycle arrest. Our results provided evidence that HIV PIs can be potentially used in combination with radiation in the treatment of HNSCC

Reusable and cross‐linked cellulose nanofibrils aerogel for the removal of heavy metal ions

Reusable and porous aerogel was fabricated using natural cellulose nanofibrils (CNFs) cross-linked with acrylic acid (AA) for the removal of heavy metal ions. CNFs with diameters of 5–50 nm were obtained and the cross-linking mechanism of CNFs with AA (CA aerogel) was analyzed. The CNFs based aerogel formed highly porous networks after cross-linking with AA and carboxyl groups were introduced onto the molecular chain of CNFs. The maximum adsorption capacities of CA aerogel for Cu(II) and Pb(II) were 40.01 and 130.36 mg/g and the adsorption closely followed the pseudo-second-order kinetic and Langmuir isothermal model for both Cu(II) and Pb(II). Chemical adsorption combined with porous physical adsorption endowed CA aerogel excellent adsorption properties. The prepared CA aerogel showed desirable reusability and could remove various heavy metal ions in industrial sewage. This resulted CA aerogel was considered to be promising alternative for conventional adsorbents in fields of sewage recovery, water purification, and soil remediation. POLYM. COMPOS., 39:4442–4451, 2018. © 2017 Society of Plastics Engineers