Ginkgetin suppresses ovarian cancer growth through inhibition of JAK2/STAT3 and MAPKs signaling pathways.

BACKGROUND: Ginkgo biloba L., a kind of traditional Chinese medicine, is always used to treat various diseases. Ginkgetin is an active biflavonoid isolated from leaves of Ginkgo biloba L., which exhibits diverse biological activities, including anti-tumor, anti-microbial, anti-cardiovascular and cerebrovascular diseases, and anti-inflammatory effects. However, there are few reports on the effects of ginkgetin on ovarian cancer (OC). HYPOTHESIS/PURPOSE: OC is one of the most common cancers with high mortality in women. The purpose of this study was to find out how ginkgetin inhibited OC and which signal transduction pathways was involved to suppress OC. METHODS: The OC cell lines, A2780, SK-OV-3 and CP70, were used for in vitro experiments. MTT assay, colony formation, apoptosis assay, scratch wound assay and cell invasion assay were used to determine the inhibitory effect of ginkgetin. BALB/c nude female mice were injected with A2780 cells subcutaneously, then treated with ginkgetin by intragastric administration. Western blot experiment was used to verify the inhibitory mechanism of OC in vitro and in vivo. RESULTS: We found that ginkgetin inhibited the proliferation and induced apoptosis in OC cells. In addition, ginkgetin reduced migration and invasion of OC cells. In vivo study showed that ginkgetin significantly reduced tumor volume in the xenograft mouse model. Furthermore, the anti-tumor effects of ginkgetin were associated with a down regulation of p-STAT3, p-ERK and SIRT1 both in vitro and in vivo. CONCLUSION: Our results suggest that ginkgetin exhibits anti-tumor activity in OC cells via inhibiting the JAK2/STAT3 and MAPK pathways and SIRT1 protein. Ginkgetin could be a potential candidate for the treatment of OC.

Allylated Curcumin Analog CA6 Inhibits TrxR1 and Leads to ROS-Dependent Apoptotic Cell Death in Gastric Cancer Through Akt-FoxO3a.

BACKGROUND: Gastric cancer is one of the leading causes of cancer-related deaths. Allylated monocarbonyl analogs of curcumin (MACs) have been reported to selectively inhibit a broad range of human cancers including gastric cancer. However, the precise molecular mechanisms underlying the inhibitory activities of MACs are not fully known. METHODS: In this study, we examined the anti-tumor activities of an allylated MAC, CA6, on gastric cancer cells and gastric cancer xenograft mouse model. The potential molecular anti-tumor mechanisms of CA6 were also elucidated. RESULTS: Our data show that CA6 exhibited significant cytotoxicity in gastric cancer cells, which was seen as an induction of G2/M cell cycle arrest and apoptosis. These activities were mediated through an elaboration of ROS levels in gastric cancer cells and induction of endoplasmic reticulum stress. CA6 increased ROS levels through directly binding to and inhibiting thioredoxin reductase R1 (TrxR1). Also, CA6-generated ROS inhibited Akt and activated forkhead O3A (FoxO3a), causing cytotoxicity in gastric cancer cells. Finally, CA6 treatment dose-dependently reduced the growth of gastric cancer xenografts in tumor-bearing mice, which was associated with reduced TrxR1 activity and increased ROS in the tumor. CONCLUSION: In summary, our studies demonstrate that CA6 inhibited gastric cancer growth by inhibiting TrxR1 and increasing ROS, which in turn activated FoxO3a through suppressing Akt. CA6 is a potential candidate for the treatment of gastric cancer.

Association between smoking during pregnancy and breastfeeding at about 2 weeks of age.

Maternal smoking during pregnancy may decrease breastfeeding, in part perhaps by decreasing milk supply; furthermore, prenatal smoking is a predictor of postpartum smoking. In this study, birth certificate data, including maternal smoking, for 1998 Oregon resident live births were linked to newborn screening data obtained from Oregon's Newborn Screening Program (NSP), allowing study of risk factors for failure to breastfeed. NSP collects information on infant feeding before newborn discharge and again at about 2 weeks postpartum. Feeding data and risk factor data were available after a probability match of the newborn screening and birth certificate data sets, respectively, for 36,324 (80.3%) of the 45,228 resident live births. Prenatal maternal tobacco use was significantly associated with failure to exclusively breastfeed at about 2 weeks of age (adjusted odds ratio = 2.08, 95% confidence interval = 1.94, 2.21). Women who smoked during pregnancy were less likely to breastfeed than women who did not smoke during pregnancy.