[Apoptosis and differentiation induced with TCLA in rat glioblastoma cells in vitro].
OBJECTIVE
To investigate the effect of conjugated trienoic fatty acids on the growth inhibition, apoptosis in rat glioblastoma cells and to elucidate its mechanism of activity.


METHODS
Rat glioblastoma cells were tested in vitro cytotoxicity, colony formation inhibition, Brdu incorporation after treatment with TCLA. Its effect of apoptosis induction was detected through Hoechst 33342 staining, cell cycle analysis. The expressions of ADPRTL1, CYP1A1 and PPAR-gamma genes were detected through RT-PCR.


RESULTS
After TCLA treatment, the proliferation of C6 cells were inhibited (40 micrommol/L, 72 h, viability 56.71% +/- 0.98%), this action acted as dose-time-dependent relations; colony formation decreased significantly (40 micrommol/L, 0) and BrdU labeling index of cancer cells decreased (63.1% +/- 1.0% vs 95.6 % +/- 1.4%); apoptotic cells increased; By FCM analysis, the apoptotic indices increased, the cells increased in G0/G1 phase, decreased in S phase, which have signigicant difference; RT-RCR showed that TCLA signigicantly increased the level of ADPRTL1, CYP1A1, and PPAR-gamma mRNA expression.


CONCLUSIONS
The findings in this experimental study suggested that TCLA has potent cytotoxicity and induction apoptosis in human and rat glioblastoma cells, its mechanism of activity might be associated with the inhibition of DNA synthesis, cell cycle arrest, up-regulation the expression of apoptosis related genes ADPRTL, CYP1A1, PPAR-gamma.
Hu
Ji-lei
JL
Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, China.
Wang
Xiu-jie
XJ
Zhou
Pei-zhi
PZ
Wang
Cheng-de
CD
Xu
Jian-guo
JG
Jiang
Shu
S
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D047495:PPAR gamma / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D000970:Antineoplastic Agents; D044243:Linoleic Acids, Conjugated; D047495:PPAR gamma; D012333:RNA, Messenger; D019363:Cytochrome P-450 CYP1A1