Abstract:
:Autophagy is a response of cancer cells to various anticancer therapies. It is designated as programmed cell death type II and characterized by the formation of autophagic vacuoles in the cytoplasm. The Akt/mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6K) and the extracellular signal-regulated kinases 1/2 (ERK1/2) pathways are two major pathways that regulate autophagy induced by nutrient starvation. These pathways are also frequently associated with oncogenesis in a variety of cancer cell types, including malignant gliomas. However, few studies have examined both of these signal pathways in the context of anticancer therapy-induced autophagy in cancer cells, and the effect of autophagy on cell death remains unclear. Here, we examined the anticancer efficacy and mechanisms of curcumin, a natural compound with low toxicity in normal cells, in U87-MG and U373-MG malignant glioma cells. Curcumin induced G(2)/M arrest and nonapoptotic autophagic cell death in both cell types. It inhibited the Akt/mTOR/p70S6K pathway and activated the ERK1/2 pathway, resulting in induction of autophagy. It is interesting that activation of the Akt pathway inhibited curcumin-induced autophagy and cytotoxicity, whereas inhibition of the ERK1/2 pathway inhibited curcumin-induced autophagy and induced apoptosis, thus resulting in enhanced cytotoxicity. These results imply that the effect of autophagy on cell death may be pathway-specific. In the subcutaneous xenograft model of U87-MG cells, curcumin inhibited tumor growth significantly (P < 0.05) and induced autophagy. These results suggest that curcumin has high anticancer efficacy in vitro and in vivo by inducing autophagy and warrant further investigation toward possible clinical application in patients with malignant glioma.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Aoki H,Takada Y,Kondo S,Sawaya R,Aggarwal BB,Kondo Ydoi
10.1124/mol.106.033167subject
Has Abstractpub_date
2007-07-01 00:00:00pages
29-39issue
1eissn
0026-895Xissn
1521-0111pii
mol.106.033167journal_volume
72pub_type
杂志文章abstract::The binding of two anthranilic acid derivatives, glafenic and floctafenic acids, to human erythrocytes and plasma proteins has been investigated in vitro by equilibrium dialysis. Despite their close chemical structures it was shown that the binding of the two compounds to serum albumin, lipoproteins, and erythrocytes ...
journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
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doi:10.1124/mol.111.072884
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journal_title:Molecular pharmacology
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abstract::Cannabinoids have been implicated in the reduction of glioma growth. The present study investigated a possible relationship between the recently shown induction of cyclooxygenase (COX)-2 expression by the endocannabinoid analog R(+)methanandamide [R(+)-MA] and its effect on the viability of H4 human neuroglioma cells....
journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
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更新日期:2002-08-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:1987-05-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.105.020057
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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journal_title:Molecular pharmacology
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doi:
更新日期:1983-03-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-10-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1990-09-01 00:00:00
abstract::The carbocyclic analogue of 5-nitro-2'-deoxyuridine (NO2dUrd), in which the sugar moiety is replaced by a cyclopentane ring and which was designated C-NO2dUrd, has been evaluated for its cytostatic, antimetabolic, and antitumor properties. The following findings are noted. C-NO2dUrd is about 500- to 2000-fold less inh...
journal_title:Molecular pharmacology
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doi:
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
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abstract::Because cytotoxicity by an alkylating agent such as N-methyl-N'-nitrosoguanidine is markedly increased in adenine methylase-deficient dam-3 Escherichia coli, it was of interest to assess whether mismatch repair was similarly important in the repair of DNA damage induced by cis-diamminedichloroplatinum(II) (CDDP). The ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1985-07-01 00:00:00
abstract::Recent studies from our laboratory have provided evidence that multiple states of the phencyclidine (PCP) receptor exist. In addition, several compounds such as PCP and the novel anticonvulsant MK-801 were found to inhibit binding more potently in the presence of Mg2+ and L-glutamate (L-GLU) than when these agents wer...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-07-01 00:00:00
abstract::Cu/Zn-superoxide dismutase (SOD)-accelerated oxidation of the benzene metabolite 1,4-hydroquinone (HQ) results in the enhanced formation of semiquinone anion radicals, electrophilic 1,4-benzoquinone (BQ), and H202. We selected bone marrow stromal cells and phiX-174 double stranded plasmid DNA as model systems to inves...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-03-01 00:00:00
abstract::EM-652 (SCH 57068) is a new orally active antiestrogen that demonstrates pure antagonistic effects in the mammary gland and endometrium. In vivo studies have shown that EM-652 is primarily glucuronidated at the 7-hydroxy position in rats and that the metabolite is present in the plasma of female monkeys and human subj...
journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-12-01 00:00:00
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