title: Normal and tumour cervical cells respond differently to vaginal lactobacilli, independent of pH and lactate.
abstract: Cervical cancer is a human papilloma virus (HPV)-related cancer, but most HPV infections are transient or intermittent and resolve spontaneously. Thus, other factors, such as cervical microflora, which are dominated by lactobacilli, must be involved in invasive cervical carcinoma development after HPV infection. Previous studies have demonstrated that lactobacilli have antitumour effects, and it is possible that vaginal lactobacilli prevent cervical cancer. Here we examined the proliferative and apoptotic responses of normal and tumour cervical cells to common vaginal lactobacilli components by investigating human normal fibroblast-like cervical (normal cervical) and HeLa (cervical tumour) cell responses to Lactobacillus gasseri and Lactobacillus crispatus. The effects of different lactobacilli components, such as culture supernatants, cytoplasmic extracts, cell-wall extracts and live cells, were determined by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, trypan blue staining, lactate dehydrogenase assay and colorimetric caspase-3 activity assay. Changes in caspase-3 and human chorionic gonadotropin β (hCGβ) expression were analysed by quantitative RT-PCR. Tumour cell growth inhibition by culture supernatants was higher than that by pH- and lactate-adjusted controls. However, the effects of the supernatants on normal cells were similar to those of lactate-adjusted controls. Apoptosis was inhibited by supernatants, which was consistent with higher hCGβ expression since hCG inhibits apoptosis. Our study demonstrated that common vaginal lactobacilli exert cytotoxic effects on cervical tumour cells, but not on normal cells, and that this cytotoxicity is independent of pH and lactate. Our results encourage further studies on the interaction between lactobacilli and cervical cells, and administration of common vaginal lactobacilli as probiotics.
authors.affiliation: Department of Medical Biotechnology, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Elahe
authors.initials: E
authors.lastname: Motevaseli
authors.affiliation: Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mahdieh
authors.initials: M
authors.lastname: Shirzad
authors.affiliation: Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Akrami
authors.affiliation: Department of Gynecology Oncology, Valli-e-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Azam-Sadat
authors.initials: AS
authors.lastname: Mousavi
authors.affiliation: Department of Microbiology, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Akbar
authors.initials: A
authors.lastname: Mirsalehian
authors.affiliation: Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Modarressi
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry*; D007778:Lactobacillus / Q000502:physiology*; D009336:Necrosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*; D014621:Vagina / Q000382:microbiology*
chemical_list: D018997:Chorionic Gonadotropin, beta Subunit, Human; D012333:RNA, Messenger; D019344:Lactic Acid; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3