Mari Tadakawa

Curcumin induces cross-regulation between autophagy and apoptosis in uterine leiomyosarcoma cells.

Objective Uterine leiomyosarcoma (LMS) has an unfavorable response to standard chemotherapy. A natural occurring compound, curcumin, has been shown to have inhibitory effects on cancers. We previously demonstrated that curcumin reduced uterine LMS cell proliferation by targeting the AKT-mTOR pathway and activating apoptosis. To further explore the anticancer effect of curcumin, we investigated the efficacy of curcumin on autophagy in LMS cells. Methods Cell proliferation in human uterine LMS cell lines, SKN and SK-UT-1, was assessed after exposure to rapamycin or curcumin. Autophagy was detected by Western blotting for light chain 3 and sequestosome 1 (SQSTM1/p62) expression. Apoptosis was confirmed by Western blotting for cleaved poly (ADP-ribose) polymerase (PARP). Results Both rapamycin and curcumin potently inhibited SKN and SK-UT-1 cell proliferation in a dose-dependent manner. Curcumin induced autophagy and apoptosis in SKN and SK-UT-1 cells, whereas rapamycin, a specific mTOR inhibitor, did not. Curcumin increased extracellular signal-regulated kinase 1/2 activity in both SKN and SK-UT-1 cells, whereas PD98059, an MEK1 inhibitor, inhibited both the extracellular signal-regulated kinase 1/2 pathway and curcumin-induced autophagy. Conclusions These experimental findings suggest that curcumin is a potent inhibitor of cell proliferation in uterine LMS and provide new insights about ongoing signaling events leading to the possible development of a new therapeutic agent.

The anti-diabetic drug metformin inhibits vascular endothelial growth factor expression via the mammalian target of rapamycin complex 1/hypoxia-inducible factor-1α signaling pathway in ELT-3 cells.

The aim of this study was to elucidate whether metformin can regulate the expression of vascular endothelial growth factor (VEGF) in rat-derived uterine leiomyoma cells (ELT-3 cells). In vitro studies were conducted using ELT-3 cells. Under normoxic conditions, metformin suppressed VEGF protein levels in the supernatant and cells in a dose-dependent manner. In hypoxia-mimicking conditions, VEGF and hypoxia-inducible factor-1α (HIF-1α) proteins were both highly expressed and were suppressed by the metformin treatment. Metformin did not affect HIF-1α mRNA levels, which indicated that its effects occurred at the post-translational level. Metformin inhibited mammalian target of rapamycin complex 1 (mTORC1) activity by phosphorylating the mTORC1 component raptor. This study revealed the anti-angiogenic activity of metformin in ELT-3 cells by suppressing the expression of VEGF via the mTORC1/HIF-1α pathway. These results indicate that metformin may represent an effective alternative in the future treatment of uterine leiomyomas.

Relationship between dysmenorrhea and posttraumatic stress disorder in Japanese high school students 9 months after the Great East Japan Earthquake.

STUDY OBJECTIVE To determine the relationship between dysmenorrhea and posttraumatic stress disorder (PTSD) among Japanese adolescent girls 9 months after the Great East Japan Earthquake. DESIGN Cross-sectional study. SETTING Two high schools in Sendai, the largest city in northeastern Japan. PARTICIPANTS 1489 female adolescents aged between 15 and 18 years. MAIN OUTCOME MEASURES Impact of Event Scale-Revised (IES-R), intensity of menstrual pain. RESULTS The intensity of menstrual pain increased according to the comorbidity of PTSD (P < .001). The IES-R subscale and total scores significantly increased according to the severity of menstrual pain. CONCLUSIONS This study showed a significant association between natural disaster-induced PTSD and the severity of dysmenorrhea.

Fertility and pregnancy outcomes following B-Lynch sutures for post-partum hemorrhage.

The aim of this study was to investigate the long‐term fertility prognosis after B‐Lynch sutures for post‐partum hemorrhage (PPH).