Abstract
Lymphoma is a blood cancer comprising various subtypes. Although effective therapies are available, some patients fail to respond to treatment and can suffer from side effects. Antioxidant systems, especially the thioredoxin (Trx) and glutathione (GSH) systems, are known to enhance cancer cell survival, with thioredoxin reductase (TrxR) recently reported as a potential anticancer target. Since the GSH system can compensate for some Trx system functions, we investigated its response in three lymphoma cell lines after inhibiting TrxR activity with [Au(d2pype)2]Cl, a known TrxR inhibitor. [Au(d2pype)2]Cl increased intracellular reactive oxygen species (ROS) levels and induced caspase-3 activity leading to cell apoptosis through inhibiting both TrxR and glutathione peroxidase (Gpx) activity. Expression of the tumour suppresser gene TXNIP increased, while GPX1 and GPX4 expression, which are related to poor prognosis of lymphoma patients, decreased. Unlike SUDHL2 and SUDHL4 cells, which exhibited a decreased GSH/GSSG ratio after treatment, in KMH2 cells the ratio remained unchanged, while glutathione reductase and glutaredoxin expression increased. Since KMH2 cells were less sensitive to treatment with [Au(d2pype)2]Cl, the GSH system may play a role in protecting cells from apoptosis after TrxR inhibition. Overall, our study demonstrates that inhibition of TrxR represents a valid therapeutic approach for lymphoma.
Highlights
Accepted: 8 January 2021Lymphoma is a type of cancer that develops in the lymphatic system
Cells were cultured in RPMI-1640 medium (Gibco, Gaithersburg, MD, USA) containing 10% (v/v) foetal bovine serum (FBS) (Bovagen, France), 200 mM of L-glutamine, 100 U/mL of penicillin and 100 μg/mL streptomycin (Gibco, Gaithersburg, MD, USA). [Au(d2pype)2]Cl was gifted by Sue Berners-Price (Glycomics, Griffith University, QLD, Australia)
It is notable that the mRNA expression levels of TXN, GPX1, GPX4, and GLRX2 were ranked in the top 1% upregulated genes in both HL and diffuse large B-cell lymphoma (DLBCL) when compared with healthy cells
Summary
Lymphoma is a type of cancer that develops in the lymphatic system. It can be divided into two subtypes: Hodgkin’s (HL) and non-Hodgkin’s lymphoma (NHL). It is reported that NHL generally has a more rapid cell growth than HL [1]. Hodgkin’s lymphoma is most commonly diagnosed in young people and adults over 55 [2]. Non-Hodgkin’s lymphoma is the fifth most common cancer type in developed countries [3]. ABVD (Doxorubicin hydrochloride, bleomycin, vinblastine sulfate, and dacarbazine) [4] and CHOP-R (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) [5] are two standard chemotherapy regimens to treat Hodgkin’s and non-Hodgkin’s lymphoma, respectively
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
