Lambertianic acid (LA) is a biologically active compound from the leaves of Pinus koraiensis. In the present study, apoptotic mechanisms of LA plus TNF-related apoptosis-inducing ligand (TRAIL) were elucidated in non-small cell lung cancer cells (NSCLCs). Cytotoxicity assay, flow cytometry, immunoprecipitation and Western blotting were performed. Here, combined treatment of LA and TRAIL increased cytotoxicity, sub-G1 population and cleaved poly (ADP-ribose) polymerase (PARP) and caspase3/8/9 in A549 and H1299 cells compared to LA or TRAIL alone. Furthermore, combined treatment of LA and TRAIL significantly decreased anti-apoptotic proteins such as B-cell lymphoma 2 (Bcl-2), Fas-like inhibitor protein (FLIP) and X-linked inhibitor of apoptosis protein (XIAP) and enhanced the activation of pro-apoptotic proteins Bid compared to LA or TRAIL alone. In addition, combined treatment of LA and TRAIL upregulated the expression of Death receptor 4 (DR4) and downregulated phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (p-NF-B), inhibitory protein of kB family (p-IB) and FLIP in A549 and H1299 cells along with disrupted binding of XIAP with caspase3 or NF-B. Overall, these findings suggest that lambertianic acid enhances TRAIL-induced apoptosis via inhibition of XIAP/NF-B in TRAIL resistant NSCLCs.

Though Moracin D derived from Morus alba was known to have anti-inflammatory and antioxidant activities, the underlying antitumor mechanism of Moracin D was never unveiled so far. Thus, in the recent study, the apoptotic mechanism of Moracin D was elucidated in breast cancer cells. Herein, Moracin D exerted significant cytotoxicity in MDA-MB231 and MCF7 cells. Also, Moracin D increased sub G1 population, cleaved poly (ADP-ribose) polymerase (PARP) and attenuated the expression of pro-cysteine aspartyl-specific protease (procaspase 3), c-Myc, cyclin D1, B-cell lymphoma 2 (Bcl-2),and X-linked inhibitor of apoptosis protein (XIAP) in MDA-MB231 cells. Of note, Moracin D reduced expression of Forkhead box M1 (FOXM1), β-catenin, Wnt3a, and upregulated glycogen synthase kinase 3 beta (GSK 3β) on Tyr216 along with disturbed binding of FOXM1 with β-catenin in MDA-MB-231 cells. Conversely, GSK3β inhibitor SB216763 reversed the apoptotic ability of Moracin D to reduce expression of FOXM1, β-catenin, pro-caspase3 and pro-PARP in MDA-MB-231 cells. Overall, these findings provide novel insight that Moracin D inhibits proliferation and induces apoptosis via suppression of Wnt3a/FOXM1/β-catenin signaling and activation of caspase and GSK3β

(1) Background: This study aimed to identify the recurrence and survival rates according to the mismatch repair (MMR), p53, and L1 cell adhesion molecule (L1CAM) states in patients with advanced and recurrent endometrial cancer receiving systemic chemotherapy.; (2) Methods: This single-center retrospective cohort study included chemotherapy-naïve patients (n=156) with advanced-stage (III/IV) or recurrent endometrial cancer who were administered chemotherapy as adjuvant therapy (n=112) or first-line palliative treatment (n=44) between January 2015 and June 2022. MMR and p53 states were assessed using PCR, and L1CAM was tested using immunohistochemistry in the no specific molecular profile (NSMP) group. The primary outcomes were progression-free survival (PFS) and overall survival (OS).; (3) Results: Of the 156 patients, 62 (39.7%), 53 (34.0%), and 41 (26.3%) had NSMP, abnormal p53 (p53abn), and an MMR deficiency (MMR-D), respectively. PFS and OS were longest in MMR-D, followed by NSMP, and were the least in p53abn tumors (PFS: p=0.0006, OS: p=0.0013). After NSMP was classified according to positive or negative L1CAM status, the L1CAM-negative group exhibited significantly lower survival rates than the L1CAM-positive group (PFS: p=0.0001, OS: p=0.0027); p53abn tumors were independent prognostic factors for poor PFS (p=0.039 on the multivariable analysis).; (4) Conclusions: In chemotherapy-naïve patients with advanced and recurrent endometrial cancer, the best prognosis after chemotherapy was obtained using MMR-D, followed by NSMP and p53abn tumors. The L1CAM status is a useful new marker for stratifying NSMP in advanced and recurrent patients.

The objective of this study is to investigate the aquatic-toxic effects of glyoxal-containing cellulose ether with four different glyoxal concentrations (0, 1.4, 2.3 and 6.3%) in response to global chemical regulations, e.g., European Union Classification, Labeling and Packaging (EU CLP). Tests of the aquatic-toxic effects of glyoxal-containing cellulose ether on 11 freeze-dried microbial strains, Microcystis aeruginosa, Daphnia magna and zebrafish embryos were designed as an initial stage for toxicity screening, and were performed with the standardized toxicity test guidelines. Glyoxal-containing cellulose ether showed no significant toxic effects in the toxicity tests for the 11 freeze-dried microbial strains, Daphnia magna and zebrafish embryos. Alternatively, 6.3% glyoxal-containing cellulose ether led to more than a 60% reduction of Microcystis aeruginosa growth after 7 days of exposure. Approximately 10% developmental abnormalities (e.g., bent spine) in zebrafish embryos were also observed in the group exposed to 6.3% glyoxal-containing cellulose ether after 6 days of exposure. These results imply that <6.3% glyoxal-containing cellulose ether results in non-toxic effects on the acute toxicity of aquatic organisms. However, ≥6.3% glyoxal-containing cellulose ether may affect the health of aquatic organisms with long-term exposure. In order to better evaluate the eco-safety of cellulosic products contained in glyoxal, further studies regarding the toxic effects of glyoxal-containing cellulose ether with long-term exposure are required. The results from this study allow us to evaluate the auatic-toxic effects of glyoxal-containing cellulosic products, under EU chemical regulations, on the health of aquatic organisms.