title: TGFβ1 induces apoptosis in invasive prostate cancer and bladder cancer cells via Akt-independent, p38 MAPK and JNK/SAPK-mediated activation of caspases.
abstract: Recent findings indicate that advanced stage cancers shun the tumor suppressive actions of TGFβ and inexplicably utilize the cytokine as a tumor promoter. We investigated the effect of TGFβ1 on the survival and proliferation of invasive prostate (PC3) and bladder (T24) cancer cells. Our study indicated that TGFβ1 decreased cell viability and induced apoptosis in invasive human PC3 and T24 cells via activation of p38 MAPK-JNK-Caspase9/8/3 pathway. Surprisingly, no change in the phosphorylation of pro-survival Akt kinase was observed. We postulate that TGFβ1 pathway may be utilized for specifically targeting urological cancers without inflicting side effects on normal tissues.
authors.affiliation: Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Al-Azayzih
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.forename: Anna
authors.initials: A
authors.lastname: Goc
authors.forename: Payaningal R
authors.initials: PR
authors.lastname: Somanath
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000096:biosynthesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000096:biosynthesis; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000096:biosynthesis; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000473:pathology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis
chemical_list: D053773:Transforming Growth Factor beta1; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D020169:Caspases