Luteolin, a flavonoid present in botanical drugs, plants, and dietary sources, has demonstrated anticancer properties against various tumors, yet its role in diffuse large B-cell lymphoma (DLBCL) remains unclear. This study aimed to uncover the molecular mechanism of luteolin in DLBCL treatment using a combination of in vitro and in vivo experiments and computational analysis. Human DLBCL cell lines U2932 and OCI-LY10 were utilized to assess luteolin’s impact on cell growth, apoptosis, cell cycle progression, and the modulation of JAK2/STAT3 pathway proteins. In vivo, a U2932 tumor-bearing nude mice model was employed to evaluate luteolin’s antitumor efficacy and its effects on JAK2/STAT3 pathway protein expression. Additionally, molecular dynamics simulations were conducted to explore the interaction between luteolin and JAK2. The findings revealed that luteolin significantly suppressed cell proliferation, induced apoptosis, and arrested the cell cycle at the G2/M phase in both cell lines. In the mouse model, luteolin effectively inhibited tumor growth and downregulated the expression of phosphorylated JAK2 and STAT3 without altering the total protein levels of JAK2 and STAT3. Computational analysis indicated stable binding of luteolin to JAK2. Collectively, these results suggest that luteolin’s anti-DLBCL activity may be mediated through the regulation of the JAK2/STAT3 signaling pathway, positioning it as a potential therapeutic agent for DLBCL.

Objective: This study aimed to investigate the performance of Pulsatilla saponin A (PsA) in diffuse large B-cell lymphoma (DLBCL) cells. Methods: Proliferation, ELISA, apoptosis, cell cycle analysis, and assays were carried out to detect the growth and apoptosis in DLBCL cells. Western blotting was used to identify the change in the protein. Results: In cell assays, PsA significantly inhibited the growth and apoptosis in DLBCL cells. The IL-10 and TNF-α of OCI-LY10 and U2932 cells were reduced after 24 h PsA treatment. Bax, cleaved PARP, and cleaved Caspase-3 were increased, while Bcl-2 and C-Myc decreased after PsA treatment. IL-10 may regulate the expression of C-Myc protein in cells by activating the JAK2/STAT3 signaling pathway. PsA can inhibit the overexpression of p-JAK2 and p- STAT3 signaling pathways induced by IL-10 stimulants. The proliferation and apoptosis induced by PsA were confirmed in DLBCL cells. Conclusion: Our findings revealed that PsA may exert its antitumor effect by causing G1 arrest and apoptosis in DLBCL cells. The mechanism of PsA regulating apoptosis in DLBCL cells is probably through the JAK2/STAT3 signaling pathway in vitro.

Background and objectives: Anthracyclines, as a type of chemotherapy drugs, are widely used in the first-line treatment of cancers. However, anthracycline-induced cardiotoxicity (AIC) in the cumulative and dose-dependent manner greatly limits the clinical application. Insufficient energy supply caused by myocardial metabolic reconstruction is an established factor for AIC. At present, the left ventricular maximum standardized uptake value (LV SUV _max ) and left ventricular mean standardized uptake value (LV SUV _mean ) detected via ¹⁸ F-fluorodeoxyglucose ( ¹⁸ F-FDG) positron emission tomography/computed tomography (PET/CT) are effective metrics reflecting alterations of myocardial metabolism after anthracycline medications, serving as promising targets for predicting the risk of AIC. To investigate AIC-induced myocardial metabolism changes by an integration of ¹⁸ F-FDG PET/CT and data-independent acquisition (DIA) proteomics, thus providing novel targets for predicting AIC. Methods: A total of 30 patients with diffuse large B-cell lymphomas and treated with anthracycline-based chemotherapy in the Hematology Department of Jiangsu Province Hospital of Chinese Medicine from December 2023 to December 2024 were enrolled. Finally, 17 participants were included as the Diffuse Large B-cell Lymphoma (DLBCL) group. Additionally, 13 non-oncologic participants without organic heart disease, who required ¹⁸ F-FDG PET/CT for disease screening, were recruited as the control group. General data, dosage of anthracyclines, physical and chemical examination findings, and cardiac function indicators were collected. ¹⁸ F-FDG PET/CT was performed before and after 6 cycles of chemotherapy in the DLBCL group, whereas the control group underwent a single scan during the same period. Serum samples were harvested for analyzing alterations of myocardial metabolism before and after chemotherapy via DIA proteomics. Results: Among 17 patients in the DLBCL group, 6 received epirubicin chemotherapy with an average dose of 59.28 ± 12.54 mg/m ² per cycle, and 11 received liposomal doxorubicin chemotherapy with an average dose of 25.21 ± 3.14 mg/m ² per cycle. Compared to the control group, no significant differences were observed in pre-chemotherapy LV SUV _max (median: 2.40, 95% CI: 2.04–2.74) and LV SUV _mean (median: 1.34, 95% CI: 1.15–1.55) in the DLBCL group ( P > 0.05). After anthracycline-based chemotherapy, both LV SUV _max (median: 4.82, 95% CI: 3.50–6.05) and LV SUV _mean (median: 1.93, 95% CI: 1.57–2.56) significantly increased compared to pre-chemotherapy values ( P < 0.05). The proportion of patients without ¹⁸ F-FDG uptake in the left ventricular myocardium significantly decreased relative to both pre-chemotherapy levels and the control group ( P < 0.001). Conversely, the proportions of patients exhibiting diffuse uptake and focal-on-diffuse uptake significantly increased compared to pre-chemotherapy measurements ( P < 0.01). Moreover, the incidence of abnormal ¹⁸ F-FDG uptake in the left ventricular myocardium was significantly higher after chemotherapy than both before treatment and in the control group ( P < 0.001). DIA proteomics showed that CPT1A, ACOX1, ECH1, and ACAT1 were significantly downregulated after anthracycline-based chemotherapy, which were mainly enriched in fatty acid metabolism. Their protein levels were negatively associated with left ventricular standardized uptake value (LV SUV). The Mantel test consistently proved a significant association between fatty acid metabolism and LV SUV. Conclusion: An integration of ¹⁸ F-FDG PET/CT and DIA proteomics reveals a decreased fatty acid oxidation (FAO) and an increased myocardial glucose uptake after anthracycline-based chemotherapy, serving as potential mechanisms of AIC. Alterations of myocardial metabolism monitored by ¹⁸ F-FDG PET/CT may represent early indicators of metabolic remodeling, potentially identifying patients at risk for AIC. Clinical Trial Registration: https://www.chictr.org.cn/ , identifier ChiCTR2400088740.