BARC/PUB/2021/1002

 
 

Camptothecin enhances I-131-rituximab-induced G1-arrest and apoptosis in Burkitt lymphoma cells

 
     
 
Author(s)

Chandan Kumar; Sharma, R.; Repaka, K. M.; Pareri, A. U.; Dash, A.
(RPhD)

Source

Journal of Cancer Research and Therapeutics, 2021. Vol. 17: pp. 943-950

ABSTRACT

Background: Rituximab  is  a  chimeric  monoclonal  antibody  against  CD20.  It  is  an  established  immunotherapeutic  agent  for non‑Hodgkin’s lymphoma. Even though rituximab has been used in clinics for decades, only 50% of the patients respond to rituximab therapy. To enhance the  in vitro effect of rituximab, it was labeled with Iodine‑131 (131I) and combined effect of 131I‑rituximab and camptothecin (CPT) was studied on a tumor cell line expressing CD20. Objective: The  aim  is  to  study  the  magnitude  of  cell  killing  and  the  underlying  mechanism  responsible  for  enhancing in vitro therapeutic efficacy.Materials and Methods: Rituximab was labeled with 131I by the iodogen method. Raji cells were pretreated with CPT (250 nM) for an hour followed by 131I ‑rituximab (0.37 and 3.7 MBq) and incubated for 24 h in a humidified atmosphere of CO2  incubator at 37°C. Subsequently, Raji cells were harvested and thoroughly washed to carry out studies of cellular toxicity, apoptosis, cell cycle, and mitogen‑activated protein kinase (MAPK) pathways. Results:  Maximal inhibition of cell proliferation and enhancement of apoptotic cell death was observed in the cells treated with the combination of CPT and 131I ‑rituximab, compared to controls of CPT‑treated and 131I ‑rituximab‑treated cells. Raji cells undergo G1 arrest after 131I ‑rituximab treatment, which leads to apoptosis and was confirmed by the downregulation of bcl xl  protein. Expression of p38 was decreased while an increase in phosphorylation of p38 was observed in the combination treatment of CPT and 131I ‑rituximab. Conclusions:  It was concluded from the findings that CPT enhanced 131I ‑rituximab‑induced apoptosis, G1 cell cycle arrest and p38 MAPK phosphorylation in Raji cells.

 
 
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