Timing of apoptosis onset depends on cell cycle progression in peripheral blood lymphocytes and lymphocytic leukemia cells

Abstract

Abstract. Apoptosis results in cell death within 10 min after initiation by Bcl-2 family proteins and mitochondria; however, cells enter the apoptotic pathway at different elapsed times after being triggered. Intrinsic factors related to chemical or physical cell damage can initiate apoptosis at a specific cell cycle phase; it is not clear whether cells insulted via an extrinsic pathway also die at a specific cell cycle phase, or how apoptosis is related to cell cycle progression in cells. To illustrate the kinetic changes of apoptosis during cell cycle progression, we examined both intrinsically and extrinsically induced apoptosis in MOLT-4 and Jurkat lymphocytic leukemia cells and in cultured peripheral blood lymphocytes (PBLs) using a recently modified annexin V and propidium iodide method, which detects cell cycle-specific apoptosis. Apoptosis predominantly occurred at a specific cell cycle phase. Leukemia cells were sensitive to induction by both intrinsic (X-rays, UV light, camptothecin, arsenic trioxide, and the traditional Chinese medicine Jinke, which is an extract of Auricularia auricula) and extrinsic factors (via Fas and TNF receptor pathways). The phase at which leukemia cells entered apoptosis depended on the nature of the insult (X-ray or UV, G1-phase; camptothecin, S-phase; arsenic, G1/S phases; Jinke, G1/S phases; and TNF or Fas ligand, G1/S phases), whereas PBLs did not exhibit such insultdependent differences. PHA-stimulated PBLs entered apoptosis, and additional cells were recruited following additional insults. Unstimulated PBLs remained unresponsive to apoptosis, and proliferating cells became insensitive to the insults after the cell cycle checkpoint was abolished by caffeine. Confluent or starving PBLs were also unresponsive to apoptotic triggers. Thus, apoptotic cell death is a cell cycle event with most, if not all, apoptosis being initiated during a particular cell cycle phase, and changes in the cell cycle result in changes in the apoptotic pattern and schedule. The coordination of apoptosis and proliferation in cells offers a mechanism for the integration of both cell cycle and apoptotic signals.

DNA damage response in resting and proliferating peripheral blood lymphocytes treated by camptothecin or X-ray

“…The expressions of apoptosis-related proteins Bcl-2, caspase-3 and caspase-9 were also consistent with the findings. The results of the study were coincident with those reported by Feng et al [21] , who reported that quiescent PBLs were insensitive to apoptosis inducers. This finding indicated that the cell cycle status was a prerequisite for apoptosis, and apoptosis was a cell cycle event.…”

Identification of previously unreported pigments among carotenoids and anthocyanins in floral petals of Delonix regia (Hook.) Raf.

“…Direct LC-MS analysis of the PC-eluted, partially purified (Sep pak C 18 cartridge) extract was possible without any risk of mass fragmentation overlapping within compounds. Investigation of the LC-MS ion fragments showed that the 5 compounds (Table 2) of the 5 resolved peaks were distinct in their fragmentation patterns showing respective molecular weights, however with different absorption maxima matching with earlier reports (Downey & Rochfort, 2008 that of compound 5 in the present study, whereas compound 2 was the second major one reported by Adje et al (2008).The high content (88 mg/100 g) of Cyanidin-3-O-rutinoside(4) has been of great current interest because of its various biological roles (Akkarachiyasit, Yibchok-Anun, Wacharasindhu, & Adisakwattana, 2011;Chitra, Ilango, Rajanandh, & Soni, 2010) of antioxidative, anticancer, antiinflammatory, anti-diabetic and in selectively killing leukemic cells by induction of oxidative stress (Feng et al, 2007). [1][2][3]7,12,3,5,7,9,11,13,15, [1][2][3]7,12,3,5,7,9,11,13,15, 4-[18-(4-hydroxy-2,6,6-trimethyl-1-cyclohexenyl)-3,7,12,16-tetramethyl-octadeca-1, 3,5,7,9,11,13,15,17-nonaenyl]-3,5,5-trimethyl-cyclohex-3-en-1-ol 7,12,16,20,3,5,7,9,11,13,15,17,19,-3,5,5-trimethylcyclohex-3-en-1-ol β-Cryptoxanthin C 40 H 56 O 552.85 (R)-3,5,5-Trimethyl-4-[3,7,12,16-tetramethyl-18-(2,6,6-trimethylc...…”

Antiproliferative effects of selective adenosine receptor agonists and antagonists on human lymphocytes: evidence for receptor-independent mechanisms

“…For Jurkat T cells, one can argue that these cells-due to their malignancy-already proliferate at a maximum degree and cannot be further stimulated, a fact we also observed for stimulation with PHA, a strong T cell mitogen which was nevertheless unable to stimulate further proliferation in Jurkat T cells (data not shown). However, the stimulating effect of caffeine on the proliferation of already stimulated PBL can be explained by the reported ability of the methylxanthine to abolish cell cycle checkpoints [45]. As already mentioned, unstimulated PBL are resting in the G 0 phase of the cell cycle after isolation and therefore show per se no mitotic and cell cycle activity.…”