Differential control of cholesterol and fatty acid biosynthesis in sensitive and multidrug-resistant LoVo tumor cells.
Multidrug resistance (MDR) describes the decrease in sensitivity of tumor cells to a wide variety of cytotoxic compounds. Although a central role has been ascribed to the P-glycoprotein (Pgp) pump in MDR, lipids also appear to be extremely important. However, their precise role in MDR is not yet fully understood. It was the aim of the present paper to gain a deeper understanding of intracellular lipid equilibrium in both sensitive and MDR tumor cells. In particular, intracellular cholesterol biosynthesis and cholesterol esterification were examined in LoVo-sensitive and Pgp-overexpressing resistant cells. The data presented seem to suggest that the higher synthesis of cholesteryl ester and triglyceride observed in resistant with respect to wild-type cells is due to a greater production of fatty acids in these cells. The results are discussed in view of the possible roles of sterol regulatory element-binding proteins and Pgp in these phenomena.
Santini
Maria Teresa
MT
Laboratorio di Ultrastrutture, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy. santini@iss.it
Napolitano
Mariarosaria
M
Ferrante
Antonella
A
Rainaldi
Gabriella
G
Arancia
Giuseppe
G
Bravo
Elena
E
D000085:Acetates / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002784:Cholesterol / Q000096:biosynthesis* / Q000097:blood; D002788:Cholesterol Esters / Q000096:biosynthesis*; D003110:Colonic Neoplasms; D004317:Doxorubicin / Q000633:toxicity; D018432:Drug Resistance, Multiple; D005230:Fatty Acids, Nonesterified / Q000096:biosynthesis*; D006801:Humans; D011865:Radioisotope Dilution Technique; D014407:Tumor Cells, Cultured
D000085:Acetates; D002250:Carbon Radioisotopes; D002788:Cholesterol Esters; D005230:Fatty Acids, Nonesterified; D004317:Doxorubicin; D002784:Cholesterol