Publication: (+)-Grandiforacin, an antiausterity agent, induces autophagic PANC-1 pancreatic cancer cell death
2
0
Issued Date
2013
Resource Type
File Type
application/pdf
ISSN
11778881
Other identifier(s)
2-s2.0-84890483880
Rights Holder(s)
Scopus
Bibliographic Citation
Drug Design, Development and Therapy. Vol 8, (2013), p.39-47
Suggested Citation
Ueda J.-Y., Athikomkulchai S., Miyatake R., Saiki I., Esumi H., Awale S. (+)-Grandiforacin, an antiausterity agent, induces autophagic PANC-1 pancreatic cancer cell death. Drug Design, Development and Therapy. Vol 8, (2013), p.39-47. doi:10.2147/DDDT.S52168 Retrieved from: https://hdl.handle.net/20.500.14740/6474
Abstract
Human pancreatic tumors are known to be highly resistant to nutrient starvation, and this prolongs their survival in the hypovascular (austere) tumor microenvironment. Agents that retard this tolerance to nutrient starvation represent a novel antiausterity strategy in anticancer drug discovery. (+)-Grandiforacin (GF), isolated from Uvaria dac, has shown preferential toxicity to PANC-1 human pancreatic cancer cells under nutrient starvation, with a PC50 value of 14.5 μM. However, the underlying mechanism is not clear. In this study, GF was found to preferentially induce PANC-1 cell death in a nutrient-deprived medium via hyperactivation of autophagy, as evidenced by a dramatic upregulation of microtubule-associated protein 1 light chain 3. No change was observed in expression of the caspase-3 and Bcl-2 apoptosis marker proteins. GF was also found to strongly inhibit the activation of Akt, a key regulator of cancer cell survival and proliferation. Because pancreatic tumors are highly resistant to current therapies that induce apoptosis, the alternative cell death mechanism exhibited by GF provides a novel therapeutic insight into antiausterity drug candidates. © 2014 Ueda et al.
Subject(s)
Amino acid
Antineoplastic agent
Camptothecin
Caspase 3
Deoxyglucose
Fluorouracil
Gemcitabine
Glucose
Grandifloracin
Mammalian target of rapamycin
Paclitaxel
Plant extract
Podophyllotoxin
Protein bcl 2
Unclassified drug
Bridged compound
Grandifloracin
Protein kinase B
Target of rapamycin kinase
AKT kinase assay
Apoptosis
Article
Autophagy
Cancer cell
Cancer cell culture
Cancer resistance
Cell assay
Cell death
Cell proliferation
Cell structure
Cell survival
Cell viability
Comparative effectiveness
Concentration response
Controlled study
Cytotoxicity
Human
Human cell
In vitro study
PANC 1 cell line
Pancreas cancer
Pancreas tumor
Pharmacodynamics
Protein expression
Protein phosphorylation
Starvation
Upregulation
Uvaria
Western blotting
Antagonists and inhibitors
Dose response
Drug effects
Pancreatic Neoplasms
Pathology
Tumor cell line
Apoptosis
Autophagy
Bridged Compounds
Cell Line, Tumor
Dose-Response Relationship, Drug
Humans
Pancreatic Neoplasms
Proto-Oncogene Proteins c-akt
TOR Serine-Threonine Kinases
Antineoplastic agent
Camptothecin
Caspase 3
Deoxyglucose
Fluorouracil
Gemcitabine
Glucose
Grandifloracin
Mammalian target of rapamycin
Paclitaxel
Plant extract
Podophyllotoxin
Protein bcl 2
Unclassified drug
Bridged compound
Grandifloracin
Protein kinase B
Target of rapamycin kinase
AKT kinase assay
Apoptosis
Article
Autophagy
Cancer cell
Cancer cell culture
Cancer resistance
Cell assay
Cell death
Cell proliferation
Cell structure
Cell survival
Cell viability
Comparative effectiveness
Concentration response
Controlled study
Cytotoxicity
Human
Human cell
In vitro study
PANC 1 cell line
Pancreas cancer
Pancreas tumor
Pharmacodynamics
Protein expression
Protein phosphorylation
Starvation
Upregulation
Uvaria
Western blotting
Antagonists and inhibitors
Dose response
Drug effects
Pancreatic Neoplasms
Pathology
Tumor cell line
Apoptosis
Autophagy
Bridged Compounds
Cell Line, Tumor
Dose-Response Relationship, Drug
Humans
Pancreatic Neoplasms
Proto-Oncogene Proteins c-akt
TOR Serine-Threonine Kinases