minocycline and 4-hydroxyestradiol

minocycline has been researched along with 4-hydroxyestradiol* in 1 studies

Other Studies

1 other study(ies) available for minocycline and 4-hydroxyestradiol

Article	Year
Minocycline suppresses interleukine-6, its receptor system and signaling pathways and impairs migration, invasion and adhesion capacity of ovarian cancer cells: in vitro and in vivo studies. PloS one, 2013, Volume: 8, Issue:4 Interleukin (IL)-6 has been shown to be a major contributing factor in growth and progression of ovarian cancer. The cytokine exerts pro-tumorigenic activity through activation of several signaling pathways in particular signal transducer and activator of transcription (STAT3) and extracellular signal-regulated kinase (ERK)1/2. Hence, targeting IL-6 is becoming increasingly attractive as a treatment option in ovarian cancer. Here, we investigated the effects of minocycline on IL-6 and its signaling pathways in ovarian cancer. In vitro, minocycline was found to significantly suppress both constitutive and IL-1β or 4-hydroxyestradiol (4-OH-E2)-stimulated IL-6 expression in human ovarian cancer cells; OVCAR-3, SKOV-3 and CAOV-3. Moreover, minocycline down-regulated two major components of IL-6 receptor system (IL-6Rα and gp130) and blocked the activation of STAT3 and ERK1/2 pathways leading to suppression of the downstream product MCL-1. In female nude mice bearing intraperitoneal OVCAR-3 tumors, acute administration (4 and 24 h) of minocycline (30 mg/kg) led to suppression of IL-6. Even single dose of minocycline was effective at significantly lowering plasma and tumor IL-6 levels. In line with this, tumoral expression of p-STAT3, p-ERK1/2 and MCL-1 were decreased in minocycline-treated mice. Evaluation of the functional implication of minocycline on metastatic activity revealed the capacity of minocycline to inhibit cellular migration, invasion and adhesion associated with down-regulation of matrix metalloproteinases (MMP)-2 and 9. Thus, the data suggest a potential role for minocycline in suppressing IL-6 expression and activity. These effects may prove to be an important attribute to the upcoming clinical trials of minocycline in ovarian cancer. Topics: Active Transport, Cell Nucleus; Animals; Cell Adhesion; Cell Line, Tumor; Cell Movement; Cell Nucleus; Estrogens, Catechol; Female; Gene Expression Regulation, Neoplastic; Humans; Interleukin-1beta; Interleukin-6; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Minocycline; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Myeloid Cell Leukemia Sequence 1 Protein; Neoplasm Invasiveness; Ovarian Neoplasms; Phosphorylation; Proto-Oncogene Proteins c-bcl-2; Receptors, Interleukin-6; Signal Transduction; STAT3 Transcription Factor	2013

Article

Year

Minocycline suppresses interleukine-6, its receptor system and signaling pathways and impairs migration, invasion and adhesion capacity of ovarian cancer cells: in vitro and in vivo studies.

PloS one, 2013, Volume: 8, Issue:4

Interleukin (IL)-6 has been shown to be a major contributing factor in growth and progression of ovarian cancer. The cytokine exerts pro-tumorigenic activity through activation of several signaling pathways in particular signal transducer and activator of transcription (STAT3) and extracellular signal-regulated kinase (ERK)1/2. Hence, targeting IL-6 is becoming increasingly attractive as a treatment option in ovarian cancer. Here, we investigated the effects of minocycline on IL-6 and its signaling pathways in ovarian cancer. In vitro, minocycline was found to significantly suppress both constitutive and IL-1β or 4-hydroxyestradiol (4-OH-E2)-stimulated IL-6 expression in human ovarian cancer cells; OVCAR-3, SKOV-3 and CAOV-3. Moreover, minocycline down-regulated two major components of IL-6 receptor system (IL-6Rα and gp130) and blocked the activation of STAT3 and ERK1/2 pathways leading to suppression of the downstream product MCL-1. In female nude mice bearing intraperitoneal OVCAR-3 tumors, acute administration (4 and 24 h) of minocycline (30 mg/kg) led to suppression of IL-6. Even single dose of minocycline was effective at significantly lowering plasma and tumor IL-6 levels. In line with this, tumoral expression of p-STAT3, p-ERK1/2 and MCL-1 were decreased in minocycline-treated mice. Evaluation of the functional implication of minocycline on metastatic activity revealed the capacity of minocycline to inhibit cellular migration, invasion and adhesion associated with down-regulation of matrix metalloproteinases (MMP)-2 and 9. Thus, the data suggest a potential role for minocycline in suppressing IL-6 expression and activity. These effects may prove to be an important attribute to the upcoming clinical trials of minocycline in ovarian cancer.

Topics: Active Transport, Cell Nucleus; Animals; Cell Adhesion; Cell Line, Tumor; Cell Movement; Cell Nucleus; Estrogens, Catechol; Female; Gene Expression Regulation, Neoplastic; Humans; Interleukin-1beta; Interleukin-6; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Minocycline; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Myeloid Cell Leukemia Sequence 1 Protein; Neoplasm Invasiveness; Ovarian Neoplasms; Phosphorylation; Proto-Oncogene Proteins c-bcl-2; Receptors, Interleukin-6; Signal Transduction; STAT3 Transcription Factor

2013