Effect of acetyl-l-carnitine on ovarian cancer cells' proliferation, nerve growth factor receptor (Trk-A and p75) expression, and the cytotoxic potential of paclitaxel and carboplatin.
OBJECTIVE
The incidence of chemotherapy induced peripheral neuropathy (CIPN) is 15-25% with platinum and taxanes. CIPN can be permanent and often requires dose reduction or change in chemotherapy. Acetyl-l-carnitine (ALCAR), an ester of l-carnitine, is used to treat CIPN in humans and in animal models. The goals of this study are: 1) examine the effects of ALCAR on ovarian cancer cells, 2) determine if ALCAR affects the cytotoxicity of standard chemotherapy on ovarian cancer cells.


METHODS
OVCAR-3 and SKOV-3 ovarian cancer lines were incubated in ALCAR containing media. Viability, proliferation, and expression of the nerve growth factor receptors (NGFR) Trk-A and p-75 were determined by flow cytometry. Cytotoxicity assays examining ALCAR's effect on paclitaxel and carboplatin were done by flow cytometry and infrared plate-reader.


RESULTS
Flow cytometry showed no change in percent live (p = 0.87) or proliferation (p = 0.95) of OVCAR-3 cells when comparing controls with up to 100 microM ALCAR. However, there was a slight but significant decrease in the proliferation of SKOV-3 cells incubated at higher ALCAR concentrations (p = < 0.01). Flow cytometry showed no difference in the viability of OVCAR-3 cells when comparing ALCAR: +/- paclitaxel (p = 1), +/- carboplatin (p = 0.8), or both (p = 0.4). Proliferation assays indicated that paclitaxel's cytotoxicity on OVCAR-3 and SKOV-3 cells was unchanged at higher ALCAR concentrations (p = < 0.01-0.4). ALCAR did not affect the expression of NGFR on OVCAR-3 or SKOV-3 cells.


CONCLUSIONS
ALCAR does not affect the cytotoxicity of paclitaxel or carboplatin. There was no increase in proliferation, or NGFR of OVCAR-3 or SKOV-3 cells exposed to ALCAR.
Engle
David B
DB
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave., H4-636, Madison, WI 53792-6188, USA. dbengle3@yahoo.com
Belisle
Jennifer A
JA
Gubbels
Jennifer A A
JA
Petrie
Sarah E
SE
Hutson
Paul R
PR
Kushner
David M
DM
Patankar
Manish S
MS
D000108:Acetylcarnitine / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D018394:CA-125 Antigen / Q000096:biosynthesis; D016190:Carboplatin / Q000008:administration & dosage; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D020800:Receptor, Nerve Growth Factor / Q000096:biosynthesis*; D020917:Receptor, trkA / Q000096:biosynthesis*
D018394:CA-125 Antigen; D020800:Receptor, Nerve Growth Factor; D000108:Acetylcarnitine; D016190:Carboplatin; D020917:Receptor, trkA; D017239:Paclitaxel