Effects of perillyl alcohol and heat shock treatment in gene expression of human lung adenocarcinoma cell line A549.
The K-Ras protein is found mutated in 42.4% of lung adenocarcinoma cases, evidencing its importance as a chemotherapeutic target. The Ras protein becomes functional after farnesylation, a post-transduction modification, allowing its attachment to the cellular membrane permitting signal transduction. Perillyl alcohol (POH) has been shown to inhibit the farnesylation of small G-proteins such as Ras. HSP70, a protein known to appear after heat shock (HS), is found over expressed in lung cancer and modifies chemotherapeutic effects. In this work, the effect of POH and HS in the gene expression of human adenocarcinoma lung cells (A549) is studied. Cells incubated with POH followed by 42 degrees C HS presented a 20.7% cellular viability decrease compared to the ones kept at 37 degrees C. A different pattern synthesis was observed for each sequences of cell treatment. Independent of the heat treatment, the amount of HSP70 was decrease by POH without modification in the amount of p53. Here it is shown that HS modified the POH effects in the ERK activation pathway by altering the phosphorylation of p44/42 in human adenocarcinoma lung cells.
Fischer
Juliana de Saldanha da Gama
Jde S
Molecular Oncology Laboratory University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro (HUCFF-UFRJ), Brazil.
Carvalho
Paulo Costa
PC
Gattass
Cerli Rocha
CR
Paschoal
Eduardo Marcos Machado
EM
da Mota e Silva
Marcelo Soares
MS
Carvalho
Maria da Gloria da Costa
Mda G
D000230:Adenocarcinoma / Q000628:therapy*; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D018869:Heat-Shock Response; D006358:Hot Temperature; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy*; D039821:Monoterpenes / Q000494:pharmacology*; D010766:Phosphorylation; D015398:Signal Transduction
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D039821:Monoterpenes; C032208:perillyl alcohol