HLJ1 is a novel caspase-3 substrate and its expression enhances UV-induced apoptosis in non-small cell lung carcinoma

Carcinogenesis is determined based on both cell proliferation and death rates. Recent studies demonstrate that heat shock proteins (HSPs) regulate apoptosis. HLJ1, a member of the DnaJ-like Hsp40 family, is a newly identified tumor suppressor protein closely related to relapse and survival in non-small cell lung cancer (NSCLC) patients. However, its role in apoptosis is currently unknown. In this study, NSCLC cell lines displaying varying HLJ1 expression levels were subjected to ultraviolet (UV) irradiation, followed by flow cytometry. Interestingly, the percentages of apoptotic cells in the seven cell lines examined were positively correlated with HLJ1 expression. Enforcing expression of HLJ1 in low-HLJ1 expressing highly invasive cells promoted UV-induced apoptosis through enhancing JNK and caspase-3 activation in NSCLC. Additionally, UV irradiation led to reduced levels of HLJ1 predominantly in apoptotic cells. The pan-caspase inhibitor, zVAD-fmk and caspase-3-specific inhibitor, DEVD-fmk, prevented UV-induced degradation of HLJ1 by the late stage of apoptosis. Further experiments revealed a non-typical caspase-3 cleavage site (MEID) at amino acid 125–128 of HLJ1. Our results collectively suggest that HLJ1 is a novel substrate of caspase-3 during the UV-induced apoptotic process

Evaluation+of+Anti-Radiation+Activity+of+Phellinus+linteus

Radiation exposure is one of the potential carcinogenic factors in our living environment. The hematopoietic system damage is the main side effect of radiation exposure. Phellinus linteus (PL), one of the medicinal fungi in East Asia, Japan, Korea and Taiwan, has been shown to have anti-cancer, anti-inflammatory and immunomodulative effects. However, it is unclear whether PL can protect against radiation injury in vivo. Herein, BALB/C mice were orally administrated with 1.5 g/kg body weight of PL extract (water:alcohol ＝ 1:1) for 2 weeks before irradiation with γ-ray (4 Gy) once per week for 3 weeks, during which no PL extract was provided. The survival rate and hematology of mice were measured during the radiation exposures. Results reveal that the survival rate (62.5%) and the body weight (21.11 ± 0.68 g) of the PL group were significantly higher than those of the radiation group (12.5%, 19.17 ± 0.62 g, respectively). Mice in the radiation group were significantly lower in white blood cells, platelets, hemoglobin and red blood cells than those of non-irradiated mice. In contrast, administration of PL partially restored these changes caused by radiation. Thus, the present study demonstrates that PL can markedly increase survival rate and partially protect against radiation injury to the blood system in mice.我們的生活環境中潛藏著許多的致癌因子，輻射暴露也是其中之一，暴露在輻射照射下所引起的副作用主要的客觀量化指標是造血系統受損。「桑黃」（Phellinus linteus）是近些年來風行於東亞地區，如：中、日、韓、台等地著名的藥用真菌，許多研究顯示桑黃具有抗癌、抗發炎及調節免疫功能，但在目前則尚未有對於輻射保護功效之探討。本研究的目的為探討桑黃萃取物（Extract of Phellinus linteus）是否能保護輻射照射對小鼠的傷害。本實驗使用直線加速器照射BALB/C小鼠，每隔一週照射一次（每次4 Gy），共照射三次。照射前先每日管餵桑黃萃取物（水：酒精＝1：1）1.5g/kg，連續二週；照射後觀察21天內的存活率及全血計數，但停止餵食桑黃萃取物。由存活率觀察出，餵食桑黃之小鼠，其存活率（62.5%）顯著高於照射組（12.5%），且餵食桑黃萃取物組體重（21.11±0.68 g）顯著高於照射組（19.17±0.62 g）。此外，經過輻射照射後之小鼠，其白血球（White blood cells,WBC）、血小板（Platelets, PLT）、血色素（Hemoglobin, Hb）及紅血球（Red blood cells, RBC）均顯著低於正常組，但是有餵食桑黃萃取物之小鼠則比沒有餵食桑黃萃取物之小鼠在全血球計數方面高，且具有顯著差異（P<0.05）。由實驗結果推測，餵食桑黃可有效提升小鼠在輻射照射後之存活率以及降低輻射對血液系統的傷害