ABSTRACT
Advanced prostate cancer cells are typically hormone independent, resistant to apoptosis and do not respond to chemotherapeutic agents. The ability of methyl jasmonate (MJ) and cis-jasmone (CJ) to inhibit growth in hormone independent prostate cancer cell lines, PC-3 and DU-145, was evaluated. CJ and MJ inhibited cell growth, induced cell cycle arrest and apoptosis. Detailed studies with the PC-3 cell line revealed that 2 mM CJ or MJ treatment resulted in caspase 3 activation and Tumor Necrosis Factor Receptor 1 (TNFR1) activation, all hallmarks of apoptosis. These phytochemicals could be useful in the management of advanced prostate cancer.
Subject(s)
Acetates/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis , Cyclopentanes/pharmacology , Oxylipins/pharmacology , Prostatic Neoplasms/metabolism , Caspase 3/biosynthesis , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , Male , Prostatic Neoplasms/pathology , Receptors, Tumor Necrosis Factor, Type I/biosynthesisABSTRACT
Plant products such as perillyl alcohol have been reported to possess anti-tumor activities against a number of human cancers though the mechanism of action has not yet been elucidated. The effects of perillyl alcohol (POH) and its metabolite perillic acid (PA) on the proliferation of non small cell lung cancer (NSCLC, A549, and H520) cells were investigated. Both POH and PA elicited dose-dependent cytotoxicity, induced cell cycle arrest and apoptosis with increasing expression of bax, p21 and caspase-3 activity in both the cell lines. Combination studies revealed that exposing the cells to an IC50 concentration of POH or PA sensitized the cells to cisplatin and radiation in a dose-dependent manner. These results indicate that POH and PA in combination therapy may have chemotherapeutic value against NSCLC.
Subject(s)
Apoptosis/drug effects , Cell Cycle/drug effects , Cyclohexenes/pharmacology , Monoterpenes/pharmacology , Antineoplastic Agents/pharmacology , Apoptosis/radiation effects , Blotting, Western , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Caspase 3/metabolism , Cell Cycle/radiation effects , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/radiation effects , Cisplatin/pharmacology , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Dose-Response Relationship, Drug , Dose-Response Relationship, Radiation , Drug Synergism , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Humans , Inhibitory Concentration 50 , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Proto-Oncogene Proteins c-bcl-2/metabolism , Radiation, Ionizing , bcl-2-Associated X Protein/metabolismABSTRACT
The jasmonates, cis-jasmone (CJ) and methyl jasmonate (MJ), were investigated for their effects against NSCLC cell lines A549 and H520. CJ or MJ inhibited the proliferation of both cell lines in a dose-dependent manner as well as induced cell cycle arrest in the G2/M phase. Apoptosis was observed following treatment with CJ or MJ as indicated by Hoechst staining and confirmed by dual annexin V-fluorescein isothiocyanate (FITC)/prodium iodide (PI) and DAPI (4',6-diamidine-2'-phenylindole dihydrochloride) staining. p38 and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation was observed with increased expression of bax, p21, and caspase-3 activity. These observations indicate that jasmonates may have a therapeutic value in the treatment of lung cancer.