PMID- 11566295
OWN - NLM
STAT- MEDLINE
DCOM- 20011101
LR  - 20190826
IS  - 0009-2797 (Print)
IS  - 0009-2797 (Linking)
VI  - 137
IP  - 3
DP  - 2001 Sep 28
TI  - Cytoskeleton-interacting activity of geiparvarin, diethylstilbestrol and 
      conjugates.
PG  - 285-305
AB  - Geiparvarin, a natural compound isolated from the leaves of Geijera parviflora, 
      inhibits the growth of various tumor cell lines with a mode of action which may 
      be attributed to its anti-microtubular activity. Our previous findings indicated 
      that geiparvarin is able to inhibit the in vitro polymerization of tubulin and to 
      derange the microtubular network in fibroblasts more effectively in the presence 
      of paclitaxel. To further explore its biological activity here we have studied 
      the effects exerted on the other components of the cytoskeleton by geiparvarin 
      and two derivatives obtained by conjugating the 3(2H)-furanone ring of 
      geiparvarin with diethylstilbestrol (DES). Firstly, observations by electron 
      microscopy confirmed anti-microtubular properties, a near-total absence of 
      microtubules is detected when tubulin is incubated with drugs in the presence of 
      paclitaxel, whereas microtubule formation is not inhibited by drugs when assembly 
      is induced by guanosine 5'-triphosphate (GTP). Immunofluorescence assays 
      demonstrated that geiparvarin and DES act in a vinblastine-like fashion, causing 
      a marked depletion of intermediate filaments while the network of microfilaments 
      is not affected. Both the conjugates alter the 'stress fibers' organization of 
      actin and disrupt the vimentin pattern; generally they derange cytoskeleton more 
      markedly than the parent compounds. The cell growth inhibiting effects of 
      geiparvarin and derivatives are dose-dependent; they vary according to the cell 
      line used, when compounds were administered either alone or simultaneously with 
      paclitaxel. Unlike other anti-microtubule agents, they do not exhibit cell-cycle 
      compartment specificity and do not influence thymidine uptake in the cell.
FAU - Bocca, C
AU  - Bocca C
AD  - Department of Experimental Medicine and Oncology, University of Torino, Corso 
      Raffaello 30, 10125, Torino, Italy. claudia.bocca@unito.it
FAU - Gabriel, L
AU  - Gabriel L
FAU - Miglietta, A
AU  - Miglietta A
LA  - eng
PT  - Journal Article
PL  - Ireland
TA  - Chem Biol Interact
JT  - Chemico-biological interactions
JID - 0227276
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Coumarins)
RN  - 3CHI920QS7 (Cytochalasin B)
RN  - 5V9KLZ54CY (Vinblastine)
RN  - 731DCA35BT (Diethylstilbestrol)
RN  - 9007-49-2 (DNA)
RN  - O0M5JB2L95 (geiparvarin)
RN  - P88XT4IS4D (Paclitaxel)
RN  - VC2W18DGKR (Thymidine)
SB  - IM
MH  - 3T3 Cells/cytology/drug effects/metabolism
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/*pharmacology
MH  - Cell Cycle/drug effects
MH  - Cell Division/drug effects
MH  - Cell Survival/drug effects
MH  - Coumarins/*pharmacology
MH  - Cytochalasin B/pharmacology
MH  - DNA/analysis/biosynthesis
MH  - Diethylstilbestrol/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique
MH  - Mice
MH  - Microtubules/*drug effects/metabolism/ultrastructure
MH  - Paclitaxel/pharmacology
MH  - Thymidine/metabolism
MH  - Vinblastine/pharmacology
EDAT- 2001/09/22 10:00
MHDA- 2001/11/03 10:01
CRDT- 2001/09/22 10:00
PHST- 2001/09/22 10:00 [pubmed]
PHST- 2001/11/03 10:01 [medline]
PHST- 2001/09/22 10:00 [entrez]
AID - S0009279701002617 [pii]
AID - 10.1016/s0009-2797(01)00261-7 [doi]
PST - ppublish
SO  - Chem Biol Interact. 2001 Sep 28;137(3):285-305. doi: 
      10.1016/s0009-2797(01)00261-7.