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

Abstract Cancer is a group of diseases characterised by abnormal and undifferentiated cell growth that has the potential to spread to other parts of the body. It is the world's second leading cause of death and morbidity. According to the GLOBOCAN 2020 report, out of 19.3 million new cancer cases and 10 million deaths reported, 544352 new cases and 259793 deaths occurred by non-Hodgkin lymphoma (NHLs). Although, numerous therapeutic approaches like, surgery, radiotherapy, chemotherapy and immunotherapy have been developed to treat cancer, limited success has been achieved, possibly due to severe side effects associated with the drugs used during chemotherapy. Therefore, deciphering the novel compound with least side effects and highly potent against cancer is urgently required. In the present study we used leaf extract of M. oleifera, well-known for its anti-cancer efficacy against different cancer cells, however, its effect on Dalton’s lymphoma, a type of spontaneously occurring T cell lymphoma originated in the thymus of DBA mice is seriously lacking. Therefore, present study was aimed to analyze the therapeutic efficacy of M. oleifera against DL cells. Our results show that leaf extract of M. oleifera (MOML) significantly induces morphological changes in DL cells followed by chromatin condensation, nuclear fragmentation, and ROS generation. We also found significant changes in mitochondrial membrane potential (ΔΨm) in a dose dependent manner. Furthermore, apoptosis of DL cells induced by cell cycle arrest at G2/M and S phase suggested that MOML could be used to treat NHL effectively

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The p27–Skp2 axis mediates glucocorticoid-induced cell cycle arrest in T-lymphoma cells

Cell Cycle ◽

10.4161/cc.25622 ◽

2013 ◽

Vol 12 (16) ◽

pp. 2625-2635 ◽

Cited By ~ 22

Author(s):

Michael K Kullmann ◽

Claudia Grubbauer ◽

Katrin Goetsch ◽

Heidelinde Jäkel ◽

Silvio R Podmirseg ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Lymphoma Cells ◽

Cycle Arrest ◽

T Lymphoma Cells ◽

T Lymphoma

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DNA damage-induced [Zn2+]i transients: correlation with cell cycle arrest and apoptosis in lymphoma cells

AJP Cell Physiology ◽

10.1152/ajpcell.00439.2001 ◽

2002 ◽

Vol 283 (2) ◽

pp. C609-C622 ◽

Cited By ~ 19

Author(s):

Paul J. Smith ◽

Marie Wiltshire ◽

Sharon Davies ◽

Suet-Feung Chin ◽

Anthony K. Campbell ◽

...

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Cell Cycle Arrest ◽

Stress Responses ◽

Damage Threshold ◽

Lymphoma Cells ◽

Cycle Arrest ◽

Competent Cells ◽

Drug Doses ◽

Induced Apoptosis

Reactive changes in free intracellular zinc cation concentration ([Zn2+]i) were monitored, using the fluorescent probe Zinquin, in human lymphoma cells exposed to the DNA-damaging agent VP-16. Two-photon excitation microscopy showed that Zinquin-Zn2+ forms complexes in cytoplasmic vesicles. [Zn2+]iincreased in both p53wt (wild type) and p53mut(mutant) cells after exposure to low drug doses. In p53mutcells noncompetent for DNA damage-induced apoptosis, elevated [Zn2+]i was maintained at higher drug doses, unlike competent p53wt cells that showed a collapse of the transient before apoptosis. In p53wt cells, the [Zn2+]i rise paralleled an increase in p53 and bax-to-bcl-2 ratio but preceded an increase in p21WAF1, active cell cycle arrest in G2, or nuclear fragmentation. Reducing [Zn2+]i, using N, N, N′, N′-tetrakis(2-pyridylmethyl)ethylenediamine, caused rapid apoptosis in both p53wt and p53mut cells, although cotreatment with VP-16 exacerbated apoptosis only in p53wt cells. This may reflect changed thresholds for proapoptotic caspase-3 activation in competent cells. We conclude that the DNA damage-induced transient is p53-independent up to a damage threshold, beyond which competent cells reduce [Zn2+]i before apoptosis. Early stress responses in p53wt cells take place in an environment of enhanced Zn2+ availability.

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Sodium butyrate induces apoptosis and cell cycle arrest in primary effusion lymphoma cells independently of oxidative stress and p21CIP1/WAF1 induction

Molecular and Cellular Biochemistry ◽

10.1007/s11010-005-9054-x ◽

2006 ◽

Vol 285 (1-2) ◽

pp. 51-59 ◽

Cited By ~ 14

Author(s):

Yi-Fen Wang ◽

Neou-Shi Chen ◽

Yu-Ping Chung ◽

Lon-Huey Chang ◽

Yee-Hsuan Chiou ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Sodium Butyrate ◽

Primary Effusion Lymphoma ◽

Lymphoma Cells ◽

Cycle Arrest

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SYK inhibition and response prediction in diffuse large B-cell lymphoma

Blood ◽

10.1182/blood-2011-02-333773 ◽

2011 ◽

Vol 118 (24) ◽

pp. 6342-6352 ◽

Cited By ~ 69

Author(s):

Shuhua Cheng ◽

Greg Coffey ◽

X. Hannah Zhang ◽

Rita Shaknovich ◽

Zibo Song ◽

...

Keyword(s):

Cell Cycle ◽

B Cell ◽

Cell Cycle Arrest ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Lymphoma Cells ◽

Cycle Arrest ◽

Large B Cell Lymphoma ◽

Bcr Signaling ◽

Large B Cell

Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, and the role of SYK in its pathogenesis is not completely understood. Using tissue microarray, we demonstrated for the first time that SYK protein is activated in 27 of 61 (44%) primary human DLBCL tissues. Among DLBCL cell lines, 7 were sensitive and 3 were resistant to a highly specific SYK inhibitor, PRT060318. In sensitive DLBCL cells, SYK inhibition blocked the G1-S transition and caused cell-cycle arrest. This effect was reproduced by genetic reduction of SYK using siRNA. A detailed analysis of the BCR signaling pathways revealed that the consequence of SYK inhibition on PLCγ2 and AKT, as opposed to ERK1/2, was responsible for cell-cycle arrest. Genetic knock-down of these key molecules decelerated the proliferation of lymphoma cells. In addition, BCR signaling can be blocked by PRT060318 in primary lymphoma cells. Together, these findings provide insights into cellular pathways required for lymphoma cell growth and support the rationale for considering SYK inhibition as a potentially useful therapy for DLBCL. The results further suggest the possibility of using PLCγ2 and AKT as biomarkers to predict therapeutic response in prospective clinical trials of specific SYK inhibitors.

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