Cancer represents a significant disease that profoundly impacts human health and longevity. Projections indicate a 47% increase in the global cancer burden by 2040 compared to 2020, accompanied by a further rise in the associated economic burden. Consequently, there is an urgent need to discover and develop new alternative drugs to mitigate the global impact of cancer. Natural products (NPs) play a crucial role in the identification and development of anticancer therapeutics. This study identified ustusolate E (UE) and its analog 11α-hydroxy-ustusolate E (HUE) from strain Aspergilluscalidoustus TJ403-EL05, and examined their antitumor activities and mechanisms of action. The findings demonstrate that both compounds significantly inhibited the proliferation and colony formation of AGS (human gastric cancer cells) and 786-O (human renal clear cell carcinoma cells), induced irreversible DNA damage, blocked the cell cycle at the G₂/M phase, and further induced apoptosis in tumor cells. To the best of the authors' knowledge, this is the first report on the anticancer effects of UE and HUE and their underlying mechanisms. The present study suggests that HUE and UE could serve as lead compounds for the development of novel anticancer drugs.
Humans ; Apoptosis/drug effects* ; TOR Serine-Threonine Kinases/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Cell Line, Tumor ; Phosphatidylinositol 3-Kinases/genetics* ; Signal Transduction/drug effects* ; Tumor Suppressor Protein p53/genetics* ; Cell Proliferation/drug effects* ; Antineoplastic Agents/pharmacology* ; Sesquiterpenes/pharmacology* ; Aspergillus/chemistry*

Objective To investigate the changes and clinical significance of serum pro-gastrin-releasing peptide (ProGRP), squamous cell carcinoma-related antigen (SCC), and carbohydrate antigen 72-4 (CA72-4) levels in patients with gastric cancer. Methods A total of 68 patients with gastric cancer (gastric cancer group), 37 patients with benign gastric lesions (benign gastric lesion group), and 30 healthy subjects (non-gastric disease group) were selected as the study participants. Serum ProGRP, SCC, and CA72-4 levels were compared among the three groups on admission. The relationships of serum ProGRP, SCC, and CA72-4 levels with pathological parameters were analyzed in the gastric cancer group. Patients in the gastric cancer group were followed up for 24-month after discharge. Multivariate Logistic regression analysis was used to identify the influencing factors of prognosis in gastric cancer patients. Receiver operating characteristic (ROC) curves were plotted and the area under the curve (AUC) was calculated to analyze the predictive value of serum ProGRP, SCC, and CA72-4 for death during follow-up in gastric cancer patients. Results The serum levels of ProGRP, SCC, and CA72-4 in the gastric cancer group were higher than those in the benign gastric lesion group and the non-gastric disease group, and the serum levels of ProGRP and CA72-4 in the benign gastric lesion group were higher than those in the non-gastric disease group (P < 0.05). In the gastric cancer group, patients with TNM stage Ⅲ to Ⅳ, moderately-lowly differentiated histological grade, and lymph node metastasis had higher serum levels of ProGRP and CA72-4 than those with stage Ⅰto Ⅱ, high differentiation, and no lymph node metastasis. Patients with moderately-lowly differentiated histological grade had higher serum levels of SCC than those with high differentiated histological grade (P < 0.05). After 24 months of follow-up, 49 patients survived (survival group) and 19 patients died (death group) in the gastric cancer group. The serum levels of ProGRP, SCC, and CA72-4 in the death group were higher than those in the survival group on admission (P < 0.05). Multivariate Logistic regression analysis showed that serum ProGRP, SCC, and CA72-4 were independent influencing factors for the prognosis of gastric cancer patients (P < 0.05). Serum ProGRP, SCC, and CA72-4 had good predictive efficacy for death during follow-up in gastric cancer patients (AUC=0.766, 0.705, 0.828), and their combined predictive efficacy was better (AUC=0.899). Conclusion The serum levels of ProGRP, SCC, and CA72-4 that are related to TNM stage, histological grade, and lymph node metastasis in patients with gastric cancer are abnormally elevated, and their combined detection has good predictive efficacy for death during follow-up.