Fluorescence spectroscopy as a biomarker in a cell culture and in a nonhuman primate model for ovarian cancer chemopreventive agents.
OBJECTIVE
The objective of this study was to compare the effects of chemopreventive agents on natural fluorescence emission of ovarian cells in a cell culture and in a primate model as a feasibility trial to monitor drug activity.


METHODS
Fluorescence emission spectra were collected from normal (NOE) and immortalized ovarian surface epithelial cells at 290, 360, and 450 nm excitation. Redox potentials were calculated and compared to % apoptosis and cell survival. Fluorescence emission spectra were collected from 18 female rhesus macaques receiving fenretinide [N-(-hydroxyphenyl)retinamide (4-HPR)] orally and/or oral contraceptive pills (OCP) or no medication. Fluorescence intensities and redox ratios were compared using a two-tailed Student's t test.


RESULTS
Apoptosis and cell survival correlated with fluorescence emission consistent with metabolically active proteins [flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide (NAD(P)H)] and the resulting redox ratio in cells grown with 4-HPR. The 4-HPR consistently inhibited cell survival in a dose dependent manner. Degree of correlation varied between different cell lines. In primates receiving 4-HPR, fluorescence emission was increased at 450 nm excitation, 550 nm emission consistent with FAD presence, whereas those receiving OCP showed decreased emission at 350 nm excitation, 450 nm emission consistent with decreased NAD(P)H presence. Redox ratios were increased by both drugs.


CONCLUSIONS
Fluorescence intensity and redox ratio appear to be altered by 4-HPR treatment in vivo and in cell culture and by OCP in vivo. Fluorescence intensity may be useful to monitor chemopreventive agents in clinical trials.
Brewer
Molly
M
University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. mbrewer@azcc.arizona.edu
Utzinger
Urs
U
Li
Yang
Y
Atkinson
E Neely
EN
Satterfield
William
W
Auersperg
Nelly
N
Richards-Kortum
Rebecca
R
Follen
Michele
M
Bast
Robert
R
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003276:Contraceptives, Oral / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D005240:Feasibility Studies; D005260:Female; D017313:Fenretinide / Q000627:therapeutic use*; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D008253:Macaca mulatta; D009249:NADP / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000517:prevention & control*; D010053:Ovary / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D010084:Oxidation-Reduction / Q000187:drug effects; D012016:Reference Values; D013050:Spectrometry, Fluorescence
D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D003276:Contraceptives, Oral; D005182:Flavin-Adenine Dinucleotide; D017313:Fenretinide; D009249:NADP