Doxorubicin hydrochloride (DOX) is an effective anticancer agent for leukemia chemotherapy, although its clinical use has been limited because of its side effects such as cardiotoxicity, alopecia, vomiting, and leucopenia. Attention has been focussed on developing new drug carriers with high adsorption capacity and rapid adsorption rate in order to minimize the side effects of DOX. Graphene oxide (GO), a new type of nanomaterial in the carbon family, was prepared by Hummers method and used as adsorbent for DOX from aqueous solution. The physico-chemical properties of GO were characterized by transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR), zeta potential, and element analysis. The adsorption properties of DOX on GO were studied as a function of contact time, adsorbent dosage, temperature and pH value. The results showed that GO had a maximum adsorption capacity of 1428.57 mg/g and the adsorption isotherm data fitted the Langmuir model. The kinetics of adsorption fits a pseudo-second-order model. The thermodynamic studies indicate that the adsorption of DOX on GO is spontaneous and endothermic in nature.

Histone deacetylases (HDACs) are involved in tumorigenesis and progression, however, their role in diffuse large B-cell lymphoma (DLBCL) is not well understood. In this study, we examined the expression levels, mutations, and clinical significance of HDACs in DLBCL. Additionally, we investigated the therapeutic potential of Chidamide, a novel HDAC inhibitor, to provide scientific evidence for targeting HDACs in DLBCL patients. We extracted transcriptome data of DLBCLs––including 47 lymph node samples and 337 whole-blood-cell controls––from The Cancer Genome Atlas. Bioinformatic analyses of HDAC expression, mutation, and correlation with the clinical significance of DLBCL patients were performed with the Gene Expression Profiling Interactive Analysis, GENEMANIA, and web-based software including cBioPortal and WebGestalt. To examine the therapeutic effect of Chidamide, DLBCL cell lines (WSU-DLCL-2 and DB cells) were employed. Cell proliferation and apoptosis were analyzed with Cell Counting Kit-8 and flow cytometry assays. The impact of Chidamide treatment was also analyzed by RNA sequencing of treated DB cells. Western blot was used to explore the molecular mechanism of the cytotoxicity of Chidamide on DLBCL cell lines. The expression of some HDACs (HDAC1, 2, 3, 4, 6, 7, 8, and 9) were significantly higher in the lymph node samples of DLBCL than that in whole-blood-cell controls. Moreover, we found that the mutation rate of HDACs was also higher in DLBCL tissues, although the overall survival of DLBCL patients was not associated with HDAC expression. Chidamide was found to have a cytotoxic effect on DLBCL cells in a dose-dependent manner, while transcriptome analysis and western blot revealed that using it for treatment impacted several biological processes, including PI3K/AKT signaling, mTOR signaling, the cell cycle, and apoptosis pathways. Alterations of HDAC genes, including enhanced expression and mutations, are positively related to DLBCL. Targeting HDACs with specific inhibitors such as Chidamide may represent a potential therapeutic approach for DLBCL patients.

The validated therapeutic effects of dihydroartemisinin (DHA) in solid tumors have encouraged us to explore its potential in treating T-cell lymphoma. We found that Jurkat cells (a T-cell lyphoma cell line) were sensitive to DHA treatment with a IC50 of dihydroartemisinin. The cytotoxic effect of DHA in Jurkat cells showed a dose- and time- dependent manner. Interestingly, the cytotoxic effect of DHA was further enhanced by holotransferrin (HTF) due to the high expression of transferrin receptors in T-cell lymphoma. Mechanistically, DHA significantly increased the production of intracellular reactive oxygen species, which led to cell cycle arrest and apoptosis. The DHA treatment also inhibited the expression of protumorgenic factors including VEGF and telomerase catalytic subunit. Our results have proved the therapeutic effect of DHA in T-cell lymphoma. Especially in combination with HTF, DHA may provide a novel efficient approach in combating the deadly disease.

Doxorubicin hydrochloride is widely used to treat various types of cancers. Its therapeutic and side effects are well documented. However, the developmental toxicity of doxorubicin has not been previously described. Lethal and sublethal effects on embryo-larval stages of zebrafish in a study of the developmental toxicity of doxorubicin were observed. Zebrafish embryos were exposed to different concentrations (0–100 mg/L) of doxorubicin between 4 and 120 h post fertilization, and zebrafish larvae were exposed to different concentrations (0–200 mg/L) of doxorubicin for 96 h. The markers about the development toxicity of doxorubicin in zebrafish were observed under a stereomicroscope. Higher doxorubicin concentrations mainly caused acute lethal effects, and lower doxorubicin concentrations mainly caused sublethal effects, such as multiple malformations in embryos and larvae. Moreover, with the increase of doxorubicin concentration, the malformation rate increased. The heart rate of embryos was accelerated at lower concentrations of doxorubicin (≤ 10 mg/L) and decelerated at higher concentrations (≥ 25 mg/L). The hatching rate and body length were inhibited at higher concentrations of doxorubicin (≥ 25 mg/L).In conclusion, doxorubicin has serious developmental toxicity and this raises a concern for developmental effects of doxorubicin in clinical practice.

This study had investigated the possible toxicity of graphene oxide and its mechanisms on multiple myeloma cells (RPMI 8226 cells) using flow cytometry and a multifunctional microplate reader. RPMI 8226 cells were cultured with various concentrations of graphene oxide, then cell viability, malondialdehyde, glutathione and apoptosis were measured. We found that graphene oxide dose-dependently reduced the viability of human multiple myeloma RPMI 8226 cells. We also found that the intracellular levels of malondialdehyde increased, whereas the levels of glutathione decreased dose-dependently. There was no obvious change in the cell apoptosis rate compared with the control group. In summary, graphene oxide is dose-dependently cytotoxic to cultured RPMI 8226 cells, and its toxicity is closely associated with increased oxidative stress.

Objective: The initial therapeutic approach for diffuse large B-cell lymphoma (DLBCL) entails a rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen. However, 40% of patients exhibit suboptimal responses, with some experiencing relapse and refractory conditions. This study aimed to explore novel therapeutic strategies and elucidate their underlying mechanisms in DLBCL. Methods: Bioinformatics techniques were employed to scrutinize correlations between the HDAC1, HDAC2, HDAC3, HDAC10, BTK, MYC, TP53, and BCL2 genes in DLBCL. In vitro experiments were conducted using DB and SU-DHL-4 cells treated with chidamide, orelabrutinib, and a combination of both. Cell viability was assessed by cell counting kit-8. Cell apoptosis and the cell cycle were determined using flow cytometry. Reactive oxygen species (ROS) production and mitochondrial function were assessed through ROS and JC-1 staining. RNA sequencing and western blot analyses were conducted to elucidate the molecular mechanisms underlying the combined action of chidamide and orelabrutinib in DLBCL cells. Results: This investigation revealed markedly enhanced antiproliferative effects when chidamide was combined with orelabrutinib. Compusyn software analysis indicated a synergistic effect of chidamide and orelabrutinib in inhibiting DLBCL cell proliferation, with a combination index (CI) < 1. This synergy further manifested as augmented cell cycle arrest, apoptosis induction, the downregulation of cell cycle-associated and antiapoptotic proteins, and the upregulation of proapoptotic proteins. Furthermore, the western blot and RNA-Seq findings suggested that combining chidamide and orelabrutinib modulated the PI3K/AKT/mTOR signaling pathway, thereby promoting DLBCL cell cycle arrest and apoptosis. Conclusion: The findings of this study provide a compelling justification for the clinical utilization of chidamide and orelabrutinib to treat relapsed/refractory DLBCL.