PMID- 12818371
OWN - NLM
STAT- MEDLINE
DCOM- 20030731
LR  - 20220317
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 66
IP  - 1
DP  - 2003 Jul 1
TI  - Investigation of anticancer mechanism of thiadiazole-based compound in human 
      non-small cell lung cancer A549 cells.
PG  - 115-24
AB  - In this study, we have synthesized several compounds and examined their cytotoxic 
      effects on human non-small cell lung cancer A549 cells. We found that GO-13 
      ((E,E)-2,5-bis[4-(3-dimethyl-aminopropoxy)styryl]-1,3,4-thiadiazole) is the most 
      effective one by the MTT assay. Furthermore, the GO-13-induced apoptotic reaction 
      was identified based on several criteria, such as negative release reaction of 
      lactate dehydrogenase and positive labeling of annexin V and terminal 
      deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) techniques. GO-13 
      induced the apoptosis in A549 cells in a concentration- and time-dependent 
      manner. The data demonstrate that the regulations of p38 mitogen-activated 
      protein kinase and protein kinase C was not involved in the GO-13-mediated 
      mechanism. However, GO-13 significantly induced a down-regulation of Bcl-X(L) 
      expression in a short-term treatment (less than 3hr), whereas stimulated 
      up-regulation of Bax expression in a long-term treatment (24hr) indicating their 
      involvement in GO-13 action. GO-13-mediated apoptosis is also positively 
      correlated with the increase in caspase-3 activity. Worth noting is the fact that 
      GO-13 did not modify the phosphorylation level of Akt/protein kinase B (PKB) 
      until a 24-hr exposure was carried out indicating that the inhibition of Akt/PKB 
      activation was involved in the late-phase apoptosis. Besides the anticancer 
      activity, GO-13 also showed equivalent anti-angiogenic activity in the nude mice 
      angiogenesis model. In summary, we conclude that GO-13 is the most effective 
      anticancer compound in our screening tests. It induced the early-phase apoptosis 
      in A549 cells via the Bcl-X(L) down-regulation, and that of the late-phase 
      through up-regulation of Bax expression as well as inhibition of Akt/PKB 
      activation.
FAU - Chou, Jui-Yi
AU  - Chou JY
AD  - School of Pharmacy, College of Medicine, National Taiwan University, No. 1, 
      Jen-Ai Road, Sect. 1, Taipei, Taiwan.
FAU - Lai, Shin-Yu
AU  - Lai SY
FAU - Pan, Shiow-Lin
AU  - Pan SL
FAU - Jow, Guey-Mei
AU  - Jow GM
FAU - Chern, Ji-Wang
AU  - Chern JW
FAU - Guh, Jih-Hwa
AU  - Guh JH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Lymphokines)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Thiadiazoles)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Casp3 protein, mouse)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Angiogenesis Inhibitors/pharmacology
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - *Apoptosis
MH  - Carcinoma, Non-Small-Cell Lung/pathology
MH  - Caspase 3
MH  - Caspases/metabolism
MH  - Endothelial Growth Factors/physiology
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/physiology
MH  - Lung Neoplasms/pathology
MH  - Lymphokines/physiology
MH  - Mice
MH  - Mice, Nude
MH  - Models, Animal
MH  - Neovascularization, Physiologic/drug effects
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Thiadiazoles/*pharmacology
MH  - Time Factors
MH  - Tumor Cells, Cultured
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
EDAT- 2003/06/24 05:00
MHDA- 2003/08/02 05:00
CRDT- 2003/06/24 05:00
PHST- 2003/06/24 05:00 [pubmed]
PHST- 2003/08/02 05:00 [medline]
PHST- 2003/06/24 05:00 [entrez]
AID - S0006295203002545 [pii]
AID - 10.1016/s0006-2952(03)00254-5 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2003 Jul 1;66(1):115-24. doi: 10.1016/s0006-2952(03)00254-5.