Evidence that PKCα inhibition in Dalton's Lymphoma cells augments cell cycle arrest and mitochondrial-dependent apoptosis

Rishi Kant Singh; Praveen Kumar Verma; Sandeep Kumar; Alok Shukla; Naveen Kumar; Sanjay Kumar; Arbind Acharya

doi:10.1016/j.leukres.2021.106772

Evidence that PKCα inhibition in Dalton's Lymphoma cells augments cell cycle arrest and mitochondrial-dependent apoptosis

Leuk Res. 2022 Feb:113:106772. doi: 10.1016/j.leukres.2021.106772. Epub 2022 Jan 5.

Authors

Rishi Kant Singh¹, Praveen Kumar Verma¹, Sandeep Kumar¹, Alok Shukla¹, Naveen Kumar¹, Sanjay Kumar¹, Arbind Acharya²

Affiliations

¹ Tumor Immunology Lab, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
² Tumor Immunology Lab, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India. Electronic address: acharya@bhu.ac.in.

PMID: 35016128
DOI: 10.1016/j.leukres.2021.106772

Abstract

Protein kinase Cα (PKCα), belonging to ser/thr protein kinase, perform various biological functions. Overexpression of PKCα has been observed in multiple human malignancies including lymphoma. However, the molecular pathogenesis and involvement of PKCα in Non-Hodgkin lymphoma (NHL) are not clearly understood. Hence, deciphering the role of PKCα in NHL management may provide a better therapeutic option. In the present study, we used selective pharmacological inhibitors Gö6976 and Ro320432 that potentially inhibit PKCα-mediated signaling in DL cells, resulting in the inhibition of cell growth and mitochondrial-dependent apoptosis. PKCα inhibition by these inhibitors also displays cell cycle arrest at the G1 phase and causes growth retardation of DL cells. Our results extended the mechanism of PKCα in NHL, and provided potential implications for its therapy.

Keywords: Apoptosis; Cell cycle; Dalton's Lymphoma cells; Non-Hodgkin lymphoma; Protein kinase C-α.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects*
Carbazoles / chemistry
Carbazoles / pharmacology*
Caspases / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Cyclin-Dependent Kinase Inhibitor p21 / genetics
G1 Phase Cell Cycle Checkpoints / drug effects*
G1 Phase Cell Cycle Checkpoints / genetics
Gene Expression Regulation / drug effects
Lymphoma, Non-Hodgkin / enzymology*
Lymphoma, Non-Hodgkin / metabolism
Lymphoma, Non-Hodgkin / pathology
Membrane Potential, Mitochondrial / drug effects
Mice
Mice, Inbred BALB C
Mitochondria / metabolism*
Mitochondria / physiology
Molecular Structure
Protein Kinase C-alpha / antagonists & inhibitors*
Protein Kinase C-alpha / metabolism
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology
Signal Transduction / drug effects
Tumor Suppressor Protein p53 / genetics

Substances

Carbazoles
Cyclin-Dependent Kinase Inhibitor p21
Protein Kinase Inhibitors
Tumor Suppressor Protein p53
Go 6976
Prkca protein, mouse
Protein Kinase C-alpha
Caspases