Indomethacin induces apoptosis and inhibits proliferation in chronic myeloid leukemia cells

Zhang, Guang Sen; Tu, C; Zhang, Gui ying; Zhou, Guang‐Biao; Zheng, Wen

doi:10.1016/s0145-2126(99)00198-8

Cited by 49 publications

(28 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The present study shows that indomethacin significantly up-regulates Bax and Bak and down-regulates Bcl-2 and Bcl xL to stimulate apoptosis in the gastric mucosal cells. Indomethacin-induced up-regulation of Bax and Bak has also been evident in the gastric cancer cell line (39) and down-regulation of Bcl-2 has also been demonstrated earlier in chronic myeloid leukemia cells (40). However, the molecular mechanism behind the up-regulation of Bax and Bak and down-regulation of Bcl-2 and Bcl xL is still not clear.…”

Section: Discussionmentioning

confidence: 96%

Lansoprazole Protects and Heals Gastric Mucosa from Non-steroidal Anti-inflammatory Drug (NSAID)-induced Gastropathy by Inhibiting Mitochondrial as Well as Fas-mediated Death Pathways with Concurrent Induction of Mucosal Cell Renewal

Maity

Bindu

Choubey³

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

We have investigated the mechanism of antiapoptotic and cell renewal effects of lansoprazole, a proton pump inhibitor, to protect and heal gastric mucosal injury in vivo induced by indomethacin, a non-steroidal anti-inflammatory drug (NSAID). Lansoprazole prevents indomethacin-induced gastric damage by blocking activation of mitochondrial and Fas pathways of apoptosis. Lansoprazole prevents indomethacin-induced up-regulation of proapoptotic Bax and Bak and down-regulation of antiapoptotic Bcl-2 and Bcl xL to maintain the normal proapoptotic/antiapoptotic ratio and thereby arrests indomethacin-induced mitochondrial translocation of Bax and collapse of mitochondrial membrane potential followed by cytochrome c release and caspase-9 activation. Lansoprazole also inhibits indomethacin-induced Fas-mediated mucosal cell death by down-regulating Fas or FasL expression and inhibiting caspase-8 activation. Lansoprazole favors mucosal cell renewal simultaneously by stimulating gene expression of prosurvival proliferating cell nuclear antigen, survivin, epidermal growth factor, and basic fibroblast growth factor. The up-regulation of Flt-1 further indicates that lansoprazole activates vascular epidermal growth factor-mediated controlled angiogenesis to repair gastric mucosa. Lansoprazole also stimulates the healing of already formed ulcers induced by indomethacin. Time course study of healing indicates that it switches off the mitochondrial death pathway completely but not the Fas pathway. However, lansoprazole heals mucosal lesions almost completely after overcoming the persisting Fas pathway, probably by favoring the prosurvival genes expression. This study thus provides the detailed mechanism of antiapoptotic and prosurvival effects of lansoprazole for offering gastroprotection against indomethacin-induced gastropathy.Non-steroidal anti-inflammatory drugs (NSAIDs), 2 commonly used for the treatment of arthritis and other musculoskeletal disorders are considered to be one of the most important causative factors for gastric damage (1-3). Although various mechanisms have been suggested for NSAID-induced gastric ulcer (4 -7), recent studies suggest that increased apoptotic cell death and simultaneous block of mucosal cell renewal play major roles in the development of mucosal lesion (8 -10). Healthy gastric mucosa is always under equilibrium between cell death and cell renewal (11, 12) and mucosal injury is developed when this balance is disturbed due to an increase in apoptosis and/or inhibition of cell proliferation (11,12). NSAIDs are shown to induce apoptosis in gastric mucosal cells through reactive oxygen species generation, cytochrome c release, activation of caspase-3, inhibition of survivin expression, and induction of Ca 2ϩ signaling (8,10,13,14). Caspase-3 activation is generally mediated through two main pathways, viz. the mitochondrial (internal) and death receptor (external) pathways (15, 16). In the mitochondrial pathway, up-regulation or activation of pro-apoptotic proteins and/or down-regulation or inactivat...

show abstract

Section: Discussionmentioning

confidence: 96%

Lansoprazole Protects and Heals Gastric Mucosa from Non-steroidal Anti-inflammatory Drug (NSAID)-induced Gastropathy by Inhibiting Mitochondrial as Well as Fas-mediated Death Pathways with Concurrent Induction of Mucosal Cell Renewal

Maity

Bindu

Choubey³

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…In addition, DNA fragmentation was clearly detected via agarose gel electrophoresis; It is well known that apoptosis is linked with the activation of endonucleases and that it results in the fragmentation of DNA into well defined fragments which is seen upon electrophoretic examination as a characteristic ladder pattern (12,32). DNA strand breaks are also known to occur during the process of apoptosis, and nicks in the DNA molecules can be detected via TUNEL assay (34); such strand breaks were shown to occur in the BV-treated lung cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Bee Venom Induces Apoptosis and Inhibits Expression of Cyclooxygenase-2 mRNA in Human Lung Cancer Cell Line NCI-H1299

et al. 2003

View full text Add to dashboard Cite

Abstract. To investigate whether bee venom (BV) induces apoptosis, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, terminal deoxynucleotidyl transferasemediated dUTP nick end-labeling assay, 4,6-diamidino-2-phenylindole staining, flow cytometric analysis, and DNA fragmentation assay were performed on NCI-H1299 lung cancer cells treated with BV. Through morphological and biochemical analyses, it was demonstrated that NCI-H1299 cells treated with BV exhibit several features of apoptosis. In addition, reverse transcription-polymerase chain reaction and prostaglandin E 2 (PGE 2 ) immunoassay were performed to verify whether BV possesses an inhibitory effect on the expression of cyclooxygenase (COX) and PGE 2 synthesis. Expression of COX-2 mRNA and synthesis of PGE 2 were inhibited by BV. These results suggest the possibility that BV may exert an anti-tumor effect on human lung cancer.

show abstract

“…The systematic fractionation of C. d. terrificus venom has revealed the presence of various toxins (convulxin, crotamine, crotoxin and gyroxin) and enzymes (5,11), some of which may exert a potentially damaging effect on cells. Some of these components can induce in treated cells a type of cell death known as apoptosis (5,23,26,40). Apoptosis is a programmed cell death with known morphological changes in the nucleus (24), actin filaments (16,27) and endoplasmic reticulum (17,32).…”

Section: Introductionmentioning

confidence: 99%

Cytoskeleton, endoplasmic reticulum and nucleus alterations in CHO-K1 cell line after Crotalus durissus terrificus (South American rattlesnake) venom treatment

Tamieti¹,

DaMatta²,

Cogo³

et al. 2007

J. Venom. Anim. Toxins incl. Trop. Dis

View full text Add to dashboard Cite

Snake venoms are toxic to a variety of cell types. However, the intracellular damages and the cell death fate induced by venom are unclear. In the present work, the action of the South American rattlesnake Crotalus durissus terrificus venom on CHO-K1 cell line was analyzed. The cells CHO-K1 were incubated with C. d. terrificus venom (10, 50 and 100g/ml) for 1 and 24 hours, and structural alterations of actin filaments, endoplasmic reticulum and nucleus were assessed using specific fluorescent probes and agarose gel electrophoresis for DNA fragmentation. Significant structural changes were observed in all analyzed structures. DNA fragmentation was detected suggesting that, at the concentrations used, the venom induced apoptosis.

show abstract

Indomethacin induces apoptosis and inhibits proliferation in chronic myeloid leukemia cells

Cited by 49 publications

References 20 publications

Lansoprazole Protects and Heals Gastric Mucosa from Non-steroidal Anti-inflammatory Drug (NSAID)-induced Gastropathy by Inhibiting Mitochondrial as Well as Fas-mediated Death Pathways with Concurrent Induction of Mucosal Cell Renewal

Lansoprazole Protects and Heals Gastric Mucosa from Non-steroidal Anti-inflammatory Drug (NSAID)-induced Gastropathy by Inhibiting Mitochondrial as Well as Fas-mediated Death Pathways with Concurrent Induction of Mucosal Cell Renewal

Bee Venom Induces Apoptosis and Inhibits Expression of Cyclooxygenase-2 mRNA in Human Lung Cancer Cell Line NCI-H1299

Cytoskeleton, endoplasmic reticulum and nucleus alterations in CHO-K1 cell line after Crotalus durissus terrificus (South American rattlesnake) venom treatment

Contact Info

Product

Resources

About