Different susceptibility of lung cell lines to inhibitors of tumor promotion and inducers of differentiation.
Histologically distinct lung tumor and normal cell lines were treated with a variety of potential inhibitors of cell growth such as inducers of cell differentiation, inhibitors of protein kinase C and inhibitors of tumor promotion. The response was assessed by 3H thymidine incorporation and cloning efficiency. Both phorbol retinoate acetate and mezerein stimulated growth in lung normal cell lines (human fibroblastic PEH cells and rat epithelial TP9 cells) while inhibiting growth in lung tumor cell lines (human small-cell cancer-derived cell line IRSC-10M and adenocarcinoma-derived cell line A549). Likewise, the hydrophobic peptide melittin did not inhibit growth and cloning efficiency of normal cells at 1 microM, a concentration which prevented proliferation in tumor cells. Protein kinase C inhibitors, chlorpromazine, trifluoperazine and 1-(5 isoquinolinylsulfonyl) 2-methylpiperazine, were much more effective on proliferation of IRSC-1OM than of A549 cells. In contrast, the latter cells were more susceptible to anti-promoters such as glycyrrhetic acid, an anti-inflammatory agent, and 3,4',2', 4'-tetrahydroxychalcone or 2,3,5-trimethyl-6 (12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone, two inhibitors of lipoxygenase, a key enzyme in arachidonate metabolism. Our results provide evidence that small-cell carcinoma-derived cells, in contrast with adenocarcinoma-derived cells, are growth-inhibited by protein kinase C inhibitors and poorly dependent on the arachidonate metabolism. This difference in responsiveness suggests that different growth signalling pathways are preferentially triggered in these histologically distinct lung tumor cell lines. As a consequence, the proper susceptibility of tumor cells to phenotype modifiers has to be taken into account in cancer therapy.
Zhu
H G
HG
IRSC Laboratories, Villejuif, France.
Tayeh
I
I
Israel
L
L
Castagna
M
M
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D004224:Diterpenes; D006034:Glycyrrhetinic Acid / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008555:Melitten / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013449:Sulfonamides / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D001095:Arachidonic Acids; D004224:Diterpenes; D013449:Sulfonamides; D013729:Terpenes; D008555:Melitten; D014268:Trifluoperazine; D016718:Arachidonic Acid; C011309:mezerein; D014212:Tretinoin; C017967:W 7; D011493:Protein Kinase C; D006034:Glycyrrhetinic Acid