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Cancer is a globally complex disease with a plethora of genetic, physiological, metabolic, and environmental variations. With the increasing resistance to current anticancer drugs, efforts have been made to develop effective cancer treatments. Currently, natural products are considered promising cancer therapeutic agents due to their potent anticancer activity and low intrinsic toxicity. Decursin, a coumarin analog mainly derived from the roots of the medicinal plant Angelica sinensis , has a wide range of biological activities, including anti-inflammatory, antioxidant, neuroprotective, and especially anticancer activities. Existing studies indicate that decursin affects cell proliferation, apoptosis, autophagy, angiogenesis, and metastasis. It also indirectly affects the immune microenvironment and can act as a potential anticancer agent. Decursin can exert synergistic antitumor effects when used in combination with a number of common clinical anticancer drugs, enhancing chemotherapy sensitivity and reversing drug resistance in cancer cells, suggesting that decursin is a good drug combination. Second, decursin is also a promising lead compound, and compounds modifying its structure and formulation form also have good anticancer effects. In addition, decursin is not only a key ingredient in several natural herbs and dietary supplements but is also available through a biosynthetic pathway, with anticancer properties and a high degree of safety in cells, animals, and humans. Thus, it is evident that decursin is a promising natural compound, and its great potential for cancer prevention and treatment needs to be studied and explored in greater depth to support its move from the laboratory to the clinic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chu, Yuan, Jiang, Wu, Xie, Zhang and Li.) more...

Dysfunction of the Hippo pathway is common in esophageal squamous carcinoma (ESCC). Chaetocin, a small molecular compound isolated from the marine fungus, exhibits potent anticancer effects. However, the anticancer effects of chaetocin on ESCC and its potential relationship to Hippo pathway remain unclear. Here, we demonstrated that chaetocin dramatically inhibited the proliferation in ESCC cells by causing cycle arrest in the M phase and activating the caspase-dependent apoptosis signaling pathway in vitro , and we also found that chaetocin induced the accumulation cellular reactive oxygen species (ROS). The RNA-seq analysis indicated that the Hippo pathway is one of the most enriched pathways after chaetocin treatment. We further revealed that chaetocin triggered the activation of Hippo pathway in ESCC cells, which is characterized by elevated phosphorylation levels of almost all core proteins in Hippo pathway, such as MST1 (Thr183), MST2 (Thr180), MOB1 (Thr35), LAST1 (Thr1079 and Ser909) and YAP (Ser127), ultimately leading to decreased nuclear translocation of YAP. Moreover, the MST1/2 inhibitor XMU-MP-1 not only partially rescued the inhibitory effect chaetocin-induced proliferation, but also rescued the chaetocin-induced apoptosis in ESCC cells. Furthermore, in vivo results confirmed the antitumor effect of chaetocin and its relationship with Hippo pathway. Taken together, our study demonstrates that chaetocin exhibits anticancer effects in ESCC via activation of Hippo pathway. These results provide an important basis for further research of chaetocin as a potential candidate for ESCC treatment. more...

Breast cancer is the most frequent cause of cancer‑related mortality among women worldwide. The present study aimed to explore the role of magnesium transporter protein 1 (MAGT1) in breast cancer and to illustrate the potential underlying molecular mechanisms. Bioinformatic analysis was performed to explore the association between MAGT1 expression and patients with breast cancer. MTT, colony formation, wound healing and Transwell assays were performed to examine the proliferative, migratory and invasive abilities of MCF‑7 cells. Western blot analysis was conducted to determine the corresponding protein expression. Chromatin immunoprecipitation and luciferase reporter assays were carried out to reveal the interaction between MAGT1 and the Kruppel‑like factor 16 (KLF16). In addition, an experimental animal model was established by the subcutaneous injection of MCF‑7 cells into BALB/c nude mice, and tumor weight and size were measured. The results revealed that MAGT1 expression was upregulated in breast cancer. MAGT1 knockdown significantly suppressed the MCF‑7 cell proliferative, migratory and invasive abilities, and downregulated the protein expression of Ki67, proliferating cell nuclear antigen, MMP2 and MMP9. MAGT1 knockdown also markedly suppressed tumor growth in vivo . Moreover, KLF6 could bind to the MAGT1 promoter and positively regulate MAGT1 expression. The inhibitory effects of KLF6 knockdown on cell proliferation, migration and invasion in vitro , and tumor growth in vivo were partly abolished by MAGT1 overexpression. On the whole, the findings of the present study suggest that MAGT1 knockdown exerts notable inhibitory effects on the progression of breast cancer, providing a potential therapeutic target for the treatment of breast cancer. more...

Chaetocin is a natural metabolite product with various biological activities and pharmacological functions isolated from Chaetomium species fungi belonging to the thiodiketopyrazines. Numerous studies have demonstrated a wide range of antitumor activities of chaetocin in vitro and in vivo. Several studies have demonstrated that chaetocin suppresses the growth and proliferation of various tumour cells by regulating multiple signalling pathways related to tumour initiation and progression, inducing cancer cell apoptosis (intrinsic and extrinsic), enhancing autophagy, inducing cell cycle arrest, and inhibiting tumour angiogenesis, invasion, and migration. The antitumor effects and molecular mechanisms of chaetocin are reviewed and analysed in this paper, and the prospective applications of chaetocin in cancer prevention and therapy are also discussed. This review aimed to summarize the recent advances in the antitumor activity of chaetocin and to provide a rationale for further exploring the potential application of chaetocin in overcoming cancer in the future., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.) more...

l-Citrulline is a nonessential amino acid with a variety of physiological functions and can be enzymatically produced by arginine deiminase (ADI, EC 3.5.3.6). The enzymatic-production approach is of immense interest because of its mild conditions, high yield, low cost, and environmental benignity. However, the major hindrances of l-citrulline industrialization are the poor thermostability and enzyme activity of ADI. Hence, in this work, directed evolution and site-directed mutagenesis aided with in silico screening, including the use of b-factor values and HoTMuSiC, were applied to a previously identified ADI from Enterococcus faecalis SK23.001 ( EfADI), and a triple-site variant R15K-F269Y-G292P was obtained. The triple-site variant displays a 2.5-fold higher specific enzyme activity (333 U mg -1 ), a lower K m value of 6.4 mM, and a 6.1-fold longer half-life ( t 1/2,45°C = 86.7 min) than wild-type EfADI. This work provides a protein-engineering strategy to improve enzyme activity and thermostability, which might be transferrable to other ADIs and enzymes. more...