Distinct Cellular Calcium Metabolism in Radiation-sensitive RKO Human Colorectal Cancer Cells

Abstract

Radiation therapy for variety of human solid tumors utilizes mechanism of cell death after DNA damage caused by radiation. In response to DNA damage, cytochrome c was released from mitochondria by activation of pro-apoptotic Bcl-2 family proteins, and then elicits massive Ca2+ release from the ER that lead to cell death. It was also suggested that irradiation may cause the deregulation of Ca2+ homeostasis and trigger programmed cell death and regulate death specific enzymes. Thus, in this study, we investigated how cellular Ca2+ metabolism in RKO cells, in comparison to radiation-resistant A549 cells, was altered by gamma (γ)-irradiation. In irradiated RKO cells, Ca2+ influx via activation of NCX reverse mode was enhanced and a decline of [Ca2+]i via forward mode was accelerated. The amount of Ca2+ released from the ER in RKO cells by the activation of IP3 receptor was also enhanced by irradiation. An increase in [Ca2+]i via SOCI was enhanced in irradiated RKO cells, while that in A549 cells was depressed. These results suggest that γ-irradiation elicits enhancement of cellular Ca2+ metabolism in radiation-sensitive RKO cells yielding programmed cell death.

TRPV1 Induced Apoptosis of Colorectal Cancer Cells by Activating Calcineurin-NFAT2-p53 Signaling Pathway

“…Recent studies have shown that Ca 2+ also contributes to some malignant behaviors in tumors, such as proliferation, invasion, migration, and metastasis [13]. The imbalance of intracellular Ca 2+ influx is closely related to the hallmarks of various cancers including colorectal cancer [14, 15]. Given that TRPV1 is a powerful nonselective Ca 2+ channel, we hypothesize that TRPV1 can affect the growth of colorectal cancer cells by regulating Ca 2+ dependent signaling.…”

Chrysin Encapsulated Copper Nanoparticles with Low Dose of Gamma Radiation Elicit Tumor Cell Death Through p38 MAPK/NF-κB Pathways

“…Additionally, chrysin exhibited anti-tumor activity against choriocarcinoma cells through modification of mitochondrial membrane potential, disruption of Ca 2+ levels in cytosol, enhancing generation of reactive oxygen species (ROS), and inducing lipid peroxidation, which affects intracellular Ca 2+ homeostasis resulting in cancer cell damage [ 86 ]. Radiation therapy employs a cell death mechanism triggered by DNA damage, which activates pro-apoptotic Bcl-2 family proteins and evokes enormous Ca 2+ release from the endoplasmic reticulum, resulting in cell death [ 87 ]. Moreover, low doses of ionizing radiation (0.1–0.5 Gy) were found to suppress intracellular (Ca 2+ ) influx in the activated rat basophilic leukemia [ 88 ].…”

“…While, chrysin showed antiproliferative activity by suppressing p38 MAPK expression, which involved JNK and NF-κB in cardiac cells [ 102 ]. Exposure to low dose of ionizing radiation was found to suppress cancer cell proliferation via suppressing p38 kinase in MCF-7 human breast cancer cells [ 103 ], inhibiting JNK as well as ERK phosphorylation [ 87 ], and down-regulating NF-κB through suppressing TNFα-induced degradation of inhibitor of kappa B (IκB) protein and release of p65 subunit to the nucleus, reducing NF-κB activity [ 104 ].…”

The European Ruminants during the “Microbunodon Event” (MP28, Latest Oligocene): Impact of Climate Changes and Faunal Event on the Ruminant Evolution

“…Moreover, the size of these teeth is significantly larger than in Prodremotherium from the old Quercy collections [ 64 ] and Pech Desse [ 17 ]. The teeth are more selenomorph than in “ Amphitragulus ” and Bedenomeryx [ 8 ], [ 68 ], [ 77 ] and the parastyle is not that anteriorly projected than observed on “ Amphitragulus ” feningrei [ 62 ], [ 78 ], [ 79 ]. Looking at the neodiagnosis proposed by Mennecart [ 8 ], these fossils include all indicating features of Dremotherium .…”