RT Journal Article
SR Electronic
T1 Comparative Effects of PP242 and Rapamycin on mTOR Signalling and NOTCH Signalling in Leukemia Cells
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 809
OP 813
VO 33
IS 3
A1 AYA ONO
A1 RYO OIKE
A1 YUKI OKUHASHI
A1 YUSUKE TAKAHASHI
A1 MAI ITOH
A1 NOBUO NARA
A1 SHUJI TOHDA
YR 2013
UL http://ar.iiarjournals.org/content/33/3/809.abstract
AB Aim: PP242 is a compound which inhibits both mammalian target of rapamycin complex-1 (mTORC1) and mTORC2. We examined the effects of PP242 and rapamycin on mTOR signalling and evaluated potential crosstalk with the NOTCH signalling in eight leukemia cell lines. Materials and Methods: We examined the effects of treatment with these inhibitors on cell growth and protein expression. Results: PP242 suppressed growth more potently than did rapamycin. In two cell lines poorly sensitive to PP242, PP242 failed to inhibit v-akt murine thymoma viral oncogene homolog (AKT) phosphorylation. Suppression of mTOR phosphorylation was weaker in myeloid cell lines. Rapamycin induced eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) hyperphosphorylation in three cell lines. Phosphorylation of both isoforms (p70 and p85) of S6 kinase (S6K) was suppressed in three cell lines; only p70 was suppressed in the others. NOTCH1 expression and activation were up-regulated by PP242 in one cell line but down-regulated in another. Conclusion: PP242 is a candidate for molecular-targeted leukemia therapy, although its effects must be evaluated on a case-by-case basis. Crosstalk was found between the mTOR and NOTCH signalling pathways.