PMID- 25487614
OWN - NLM
STAT- MEDLINE
DCOM- 20150709
LR  - 20211203
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 36
IP  - 4
DP  - 2015 Apr
TI  - Staurosporine analogs promote distinct patterns of process outgrowth and 
      polyploidy in small cell lung carcinoma cells.
PG  - 2725-35
LID - 10.1007/s13277-014-2897-6 [doi]
AB  - We have recently shown that staurosporine mediates the conversion of small cell 
      lung carcinoma (SCLC) cells into a neuron-like process-bearing phenotype. Here, 
      we have extended these studies to the staurosporine analogs K252a, lestaurtinib, 
      PKC412, stauprimide, and UCN-01 and analyzed their influence on process 
      extension, cell cycle distribution, and induction of polyploidy in four SCLC cell 
      lines. In GLC-2 cells, all compounds provoked extensive process formation with 
      the exception of PKC412 that showed no response. In H1184 cells, process 
      formation was predominantly induced by staurosporine and, to lesser extent, in 
      lestaurtinib-, stauprimide-, and UCN-01-treated cells. In the presence of K252a 
      or PKC412, cells became bipolar and spindle shaped or showed pronounced cell 
      flattening. In GLC-36 and SCLC-24H cells, only cell flattening was detectable. 
      Process formation was reversible upon drug removal as shown for GLC-2 and H1184 
      cells. Fluorescence-activated cell sorting (FACS) and fluorescence in situ 
      hybridization (FISH) analysis indicated the induction of polyploidy in all 
      staurosporine and in two out of four stauprimide-treated SCLC cell lines. For 
      other staurosporine analogs, polyploidy was observed only in UCN-01-treated 
      GLC-36 cells and in K252a-treated H1184 and GLC-36 cells. The presence of 
      staurosporine or its analogs did not alter the constitutive activation pattern of 
      the canonical Akt/PI3K or MEK/extracellular signal-regulated kinase (ERK)1/2 
      signaling pathways nor could we detect an influence of stauprimide application on 
      the expression level of the c-Myc oncogene. These data demonstrate that in SCLC 
      cells, albeit a higher substrate specificity, staurosporine analogs can induce 
      staurosporine-comparable effects.
FAU - Gallala, Hichem
AU  - Gallala H
AD  - Department of Hematology/Oncology, University of Bonn, Bonn, Germany.
FAU - Winter, Jochen
AU  - Winter J
FAU - Veit, Nadine
AU  - Veit N
FAU - Nowak, Michael
AU  - Nowak M
FAU - Perner, Sven
AU  - Perner S
FAU - Courts, Cornelius
AU  - Courts C
FAU - Kraus, Dominik
AU  - Kraus D
FAU - Janzen, Viktor
AU  - Janzen V
FAU - Probstmeier, Rainer
AU  - Probstmeier R
LA  - eng
PT  - Journal Article
DEP - 20141207
PL  - Netherlands
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental 
      Biology and Medicine
JID - 8409922
RN  - 0 (Carbazoles)
RN  - 0 (Furans)
RN  - 0 (Indole Alkaloids)
RN  - 97161-97-2 (staurosporine aglycone)
RN  - DO989GC5D1 (lestaurtinib)
RN  - H88EPA0A3N (Staurosporine)
RN  - ID912S5VON (midostaurin)
SB  - IM
MH  - Carbazoles/administration & dosage
MH  - Cell Cycle/*drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/*drug effects
MH  - Furans
MH  - Humans
MH  - Indole Alkaloids/administration & dosage
MH  - Polyploidy
MH  - Signal Transduction/drug effects
MH  - Small Cell Lung Carcinoma/*drug therapy/pathology
MH  - Staurosporine/*administration & dosage/analogs & derivatives
EDAT- 2014/12/10 06:00
MHDA- 2015/07/15 06:00
CRDT- 2014/12/10 06:00
PHST- 2014/08/23 00:00 [received]
PHST- 2014/11/26 00:00 [accepted]
PHST- 2014/12/10 06:00 [entrez]
PHST- 2014/12/10 06:00 [pubmed]
PHST- 2015/07/15 06:00 [medline]
AID - 10.1007/s13277-014-2897-6 [doi]
PST - ppublish
SO  - Tumour Biol. 2015 Apr;36(4):2725-35. doi: 10.1007/s13277-014-2897-6. Epub 2014 
      Dec 7.