All trans retinoic acid sensitizes colon cancer cells to hyperthermia cytotoxic effects.
The effects of all trans retinoic acid and hyperthermia were studied in the human colon adenocarcinoma cell line HT29. Cell cytotoxicity after exposure to ATRA or heat-shock, alone or in association, was evaluated by the MTT assay while cell surface and ultrastructure modifications and actin fibre assembly changes were investigated by electron microscopy and by the FITC-phalloidin method. Apoptosis was evaluated by flow cytofluorimetry and electron microscopy. Reverse transcriptase-polymerase chain reaction was employed to study mRNA expression of genes involved in apoptosis, differentiation and growth arrest. Joint treatments were more effective in reducing the vital cell yield, being this effect only partially due to apoptosis. A marked up-regulation of the cyclin-dependent kinase inhibitor p21WAF1/Cip1 expression, not followed by any differentiation process, was responsible for growth arrest. Modulation of Hsp-70 expression, involved in cell response to treatments, was considered. Our results demonstrate that cell treatment with ATRA followed by heat-shock may elicit useful effects to treat tumours, which are responsive to retinoids, as well as those malignant cells which may be constitutively thermotolerant.
Callari
Daniela
D
Sezione di Patologia Clinica ed Oncologia Molecolare, Dipartimento di Scienze Biomediche, Università di Catania, Via Androne 83, I-95124 Catania, Italy. dcallari@unict.it
Sinatra
Fulvia
F
Paravizzini
Gianluca
G
Libra
Massimo
M
Emmanuele
Giovanni
G
Fiore
Barbara
B
Pezzino
Maria Francesca
MF
Rasà
Daria
D
Mazzarino
Maria Clorinda
MC
D'Alessandro
Natale
N
Travali
Salvatore
S
D000199:Actins / Q000378:metabolism; D017209:Apoptosis; D002454:Cell Differentiation; D002455:Cell Division; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000628:therapy*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D005434:Flow Cytometry; D006358:Hot Temperature; D006801:Humans; D006979:Hyperthermia, Induced; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013696:Temperature; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation
D000199:Actins; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D012333:RNA, Messenger; D014212:Tretinoin; D012313:RNA