C. albicans activates cyclooxygenase but not its product prostaglandin E₂in HPV 16-stabilized cells.
OBJECTIVE
The selective induction of cyclooxygenase-2 (COX-2) in human cells by Candida albicans was the first report of its role in infectious disease. This led us to question whether recurrent vulvovaginal candidosis in the cancer patient is involved in the formation of malignant tumors of the genital tract. Our speculation coincided with the patients' assessments in our hospital, where few cancer patients had a prior history of Candida infection. We wanted to study the contribution of C. albicans to gynecological cancers.


METHODS
In the present study, we used the developed vaginal epithelial cells system, having an insertion of HPV 16 viral sequence, as a model system (VK2/E6E7) to investigate the effect of Candida infection on prostaglandin E₂ synthesis, which is known to be associated with cancers. We infected VK2/E6E7 cells with wild-type C. albicans and determined its effect on COX-2 and prostaglandin E₂ synthesis, and its alteration in dependence on p53, and we analyzed the ubiquitin-proteasome degradation pathways and the involvement of 14-3-3 protein, which is involved in the modulation of the cell cycle.


RESULTS
Our work using the cellular model indicates that recurrent Candida infection of the genital tract in patients carrying HPV 16 viral infection blocks the proliferation of host cells, PGE2 synthase expression and thus PGE2 production.


CONCLUSIONS
We found that Candida infection contributes only to cell cycle arrest and does not by itself contribute actively to the development of cancer, although it is associated with patients diagnosed as having cancer of the genital tract induced by HPV 16 virus.
Deva
Rupal
R
Eicosanoid & Lipid Research Division and Centre for Experimental Gynecology & Breast Research, Charité - University Medical Centre Benjamin Franklin, D-12200 Berlin, Germany. rupal.deva@gmail.com
Sczepanski
Marco
M
Saha
Sipra
S
Zafiriou
Maria-Patapia
MP
Kerstin
Nadia
N
Jakobsson
Per-Johan
PJ
Inoue
Yuichi
Y
Nigam
Santosh
S
D048948:14-3-3 Proteins / Q000096:biosynthesis; D002176:Candida albicans / Q000502:physiology*; D002181:Candidiasis, Vulvovaginal / Q000503:physiopathology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis*; D004790:Enzyme Induction; D005260:Female; D016195:G2 Phase / Q000187:drug effects; D005833:Genital Neoplasms, Female / Q000821:virology; D006367:HeLa Cells; D052162:Human papillomavirus 16 / Q000235:genetics; D006801:Humans
D048948:14-3-3 Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone