PubMed Health⌕ Search

Biomedical subjects

M Saeed Sheikh

Publications and source records attributed to M Saeed Sheikh.

23 records · Page 2Linked to original sources
PubMedDate not supplied

Paclitaxel-induced FasL-independent apoptosis and slow (non-apoptotic) cell death.

Microtubule-active drugs, including paclitaxel (Taxol, PTX), cause mitotic arrest, and this can result in apoptosis. A recently study has reported that PTX mediates apoptosis by upregulating FasL in Jurkat and MDA-231 cells. In contrast to the previous report, we found that anti-FasL antibodies failed to inhibit PTX-induced apoptosis in Jurkat cells. In MDA-231 cells, neither FasL nor PTX induced apoptosis. In these cells, PTX caused slow cell death without activation of caspase-3 or -8 or PARP cleavage. Doxorubicin at cytostatic concentrations did not affect FasL-induced apoptosis but inhibited PTX-induced apoptosis in Jurkat cells. Following PTX-induced mitotic arrest Jurkat cells undergo apoptosis, whereas MDA-MB-231 cells exit mitosis and form multinucleated cells which then die in a slower non-apoptotic manner.

Antineoplastic Agents, Phytogenic↗
PubMedDate not supplied

Death receptor 5 regulation during selenium-mediated apoptosis in human prostate cancer cells.

Selenium is an essential micronutrient that is currently being tested for prostate cancer chemoprevention. In spite of its significant promise as a chemopreventive agent, the molecular mechanisms of selenium-mediated effects remain to be elucidated. Recent evidence suggests that selenium may mediate its chemopreventive effects by inducing apoptosis in human prostate cancer cells. Here we report that selenium-mediated apoptosis appears to involve membrane death receptor, DR5-dependent pathway in human prostate cancer cells. Selenium specifically upregulated DR5 expression but not that of DR4. Selenium upregulation of DR5 was coupled with caspase 8 activation and Bid cleavage thereby suggesting the existence of a potential cross-talk between the DR5 and the mitochondrial pathways. Thus, our results suggest that DR5 is specifically regulated by selenium and its activation may play an important role in selenium-mediated chemoprevention.

Antioxidants↗
PubMedDate not supplied

The FADD is going nuclear.

Fas-associated death domain protein (FADD) is an adaptor molecule that bridges the interactions between membrane death receptors and initiator caspases. Thus, the site of its action has always been expected to be the cytoplasmic death-inducing signaling complex (DISC). Recent evidence indicates that FADD primarily resides in the nucleus and appears to shuttle between nucleus and cytoplasm. In addition to its well-established role in transduction of apoptotic signals, FADD may also play a role in regulating genome surveillance and perhaps in other as yet unidentified cellular processes.

Active Transport, Cell Nucleus↗
PubMedDate not supplied

Death receptor activation complexes: it takes two to activate TNF receptor 1.

The extrinsic pathway of apoptosis originates at the membrane and engages membrane death receptors. Tumor necrosis factor receptor 1 (TNF-R1) is a death receptor that transduces both the death and survival signals but the molecular mechanisms via which TNF-R1 mediates these signals remain poorly understood. Recently, it has been reported that the TNF-R1 transduces these signals via two signaling complexes. The first complex (complex I) is formed at the membrane by TNF-R1, TRADD, RIP, TRAF2 and c-IAP1, while the second complex (complex II), formed in the cytosol, predominantly contains FADD and pro-caspases 8/10 but lacks TNF-R1. Complex I is responsible for activating NF-kappaB and thus, the transduction of survival signals. Complex II, on the other hand, is reported to transduce the apoptotic signals and it does so only if NF-kappaB is unable to promote upregulation of the anti-apoptotic FLIPL. These findings highlighting the complexities of TNF-R1-mediated signaling events are likely to further the progress in the constantly evolving area of death receptor-dependent signaling pathways.

Antigens, CD↗