Possible mediators underlying Linalool effect on HepG-2 but not primary hepatocytes: Comparative study

Linalool is the major component of coriander-sativum seeds. We have recently reported (1) a 100%-decrease in the viability of HepG2 treated with 2µM linalool. No effect was observed with other cell lines. Linalool resulted in a decrease in the ATP and GSH levels; increase in ROS; and inhibition of ETC-complexes I and II. ROS are known to affect level of UCP2 and ANT. Recent report showed Leukemias cells treated with linalool induced apoptosis mediated by P-53 up-regulation (2). We investigate the effect of linalool on 10ry -hepatocytes, variation in UCP2, ANT and P53 expression in HepG2 and 10ry-hepatocytes.

Viability of 1ory- hepatocytes (3), treated with varying concentration of linalool was determined using MTT assay. Expression of P53, ANT, & UCP2 in 10ry- hepatocytes was compared to those of HepG2 cells, using western blotting and was expressed relative to GAPDH.

We report that: a) 10ry-hepatocytes were not sensitive to linalool treatment; Comparing 1ory-hepatocytes to HepG2 cells, a 250 fold of linalool concentration was needed to demonstrate a 100% b) Increase in P53 expression was obtained in HepG-2 cells whereas P53 was not detected in 10ry- hepatocytes; c) Down regulated of the expression of ANT and UCP-2 in HepG-2 cells.

Linalool effect is specific to HepG2 cells but had no significant effect on 10ry- hepatocytes. There is a role of P53, and the mitochondrial proteins ANT and UCP2 in rendering HepG2 cells more sensitive. Biotransformation into toxic metabolites of linalool by HepG2 cells, but not 10ry -hepatocytes, may not be disregarded.

Acknowledgement: Medical Practice Plan and University research Board at the American University of Beirut

References: 1. Usta J et al. (2009) Chem- Biol Interact 180: 39–46

2. Gu Y et al. (2010) Toxicology 268:19–24

3. Schaffner I et al. (2005) Assay Drug Dev Technol 3(1)27–38