Carboxyethyl γ-aminobutyric acid, a polyamine derivative molecule with a growth effect on hybridomas

Cerino, Antonella; Amici, Mara De; Fussi, F; Ricotti, G.

doi:10.1016/0022-1759(85)90035-3

Cited by 6 publications

(1 citation statement)

References 7 publications

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“…Despite the lack of documentation of GABA receptor expression in malignant cells and/or tissues, we and others (2,4,15,17,34,36,40) have reported that Fig. 10: Representative photomicrograph of Chang cells transfected with GABAA-␤3 receptor cDNA (left) or vector alone (right).…”

Section: Discussionmentioning

confidence: 99%

Increasing cell membrane potential and GABAergic activity inhibits malignant hepatocyte growth

Sun¹,

Gong²,

Kojima³

et al. 2003

American Journal of Physiology-Gastrointestinal and Liver Physi

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Increasing hepatocyte membrane potentials by augmenting GABAergic activity inhibits nonmalignant hepatocyte proliferative activity. The objectives of this study were to document 1) potential differences (PDs) of four malignant hepatocyte cell lines, 2) GABAA receptor mRNA expression in the same cell lines, and 3) effects of restoring malignant hepatocyte PDs to levels approximating those of resting, nonmalignant hepatocytes. Hepatocyte PDs were documented in nonmalignant and malignant (Chang, HepG2, HuH-7, and PLC/PRF/5) hepatocytes with a fluorescent voltage-sensitive dye and GABAA receptor expression by RT-PCR and Western blot analyses. Compared with nonmalignant human hepatocytes, all four malignant cell lines were significantly depolarized (P < 0.0001, respectively). Only PLC/PRF/5 cells had detectable GABAA-beta3 receptor mRNA expression and all cell lines were negative for GABAA-beta3 receptor protein by Western blot analysis. Stable transfection of Chang cells with GABAA-beta3 receptor cDNA resulted in significant increases in PD and decreases in proliferative activity as manifest by decreased [3H]thymidine and bromodeoxyurieine incorporation rates, 4-[3-(4-lodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate activity, a lower mitotic index, prolongation of cell-doubling times, and attenuated growth patterns compared with cells transfected with vector alone. Colony formation in soft agar and the number of abnormal mitoses were also significantly decreased in GABAA-beta3 receptor transfected cells. The results of this study indicate 1) relative to healthy hepatocytes, malignant hepatocytes are significantly depolarized, 2) GABAA-beta3 receptor expression is absent in malignant hepatocyte cell lines, and 3) increasing the PD of malignant hepatocytes is associated with less proliferative activity and a loss of malignant features.

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