The circHMGCS1-miR-205-5p-ErBB3 axis mediated the Sanggenon C-induced anti-proliferation effects on human prostate cancer.

Prostate cancer (PCa) is associated with a high incidence and metastasis rate globally, resulting in an unsatisfactory prognosis and a huge economic burden due to the current deficient of therapeutic strategies. As the most abundant component of Cortex Mori, Sanggenon C (SC) is well known to possess bioactivities in tumors, but its mechanism is poorly understood. Consequently, we attempted to investigate whether SC could modulate circular RNA(s) levels and hence anti-PCa development. We found that SC dramatically promoted cell apoptosis and induced G0/G1 phase arrest in PCa cell lines via the circHMGCS1-miR-205-5p-ErBB3 axis. In brief, circHMGCS1 is highly expressed in PCa and is positively correlated with the degree of malignancy. Over-expression of circHMGCS1 is not only associated with the proliferation of PCa cells but also blocks SC-induced pro-apoptotic effects. As a verified sponge of circHMGCS1, miR-205-5p is down-regulated in PCa tumors, which negatively regulates PCa cell proliferation by modulating ErBB3 expression. After miR-205-5p mimics or inhibitors were used to transfect PCa cells, the effects of circHMGCS1 OE and SC on PCa cells were completely diminished. Similar to miR-205-5p inhibitors, siErBB3 could oppose SC-triggered pro-apoptotic effects on PCa cells. All these results were confirmed in vivo. Together, SC exerts its anti-tumor effects on PCa by inhibiting circHMGCS1 expression and results in the latter losing the ability to sponge miR-205-5p. Subsequently, unfettered miR-205-5p could mostly down-regulate ErBB3 expression by binding to the 5'UTR of ErBB3 mRNA, which eventually resulted in PCa cell cycle arrest and pro-apoptosis.

Ailanthone Inhibits Cell Proliferation in Tongue Squamous Cell Carcinoma via PI3K/AKT Pathway.

Tongue squamous cell carcinoma (TSCC) is the most widespread and invasive subtype of oral cancer with high recurrence rates. Ailanthone (AIL) is an active ingredient in the plant extracts of Ailanthus altissima (Mill.) Swingle. Here, we showed that AIL inhibited the proliferation of human TSCC, the cell viability of Cal-27 and Tca8113 was significantly decreased after AIL treatment for 24 h. Hoechst 33258 staining demonstrated apoptotic characteristics (such as chromatin aggregation) after AIL treatment. The ratio of early- and late-apoptotic cells in AIL-treated Cal-27 and TCA8113 cells increased remarkably when compared with the control group. Bcl-2/Bax ratio and the levels of PARP1, caspase-9, and caspase-3 decreased after AIL treatment, accompanied by significant increase of cleaved PARP1, cleaved caspase-9, and caspase-3 in Cal-27 and TCA8113 cells. Meanwhile, AIL led to Cal-27 cell cycle arrest at G2/M phase. Western blot implied decreased levels of CDK1 and cyclin B1 after AIL treatment. The level of phospho-PI3K p55 subunit and p-Akt were significantly downregulated by AIL in both Cal-27 and TCA8113 cells. These findings implied the potential applications of AIL in the treatment of human TSCC.

Picropodophyllin Inhibits the Proliferation of Human Prostate Cancer DU145 and LNCaP Cells via ROS Production and PI3K/AKT Pathway Inhibition.

The reactive oxygen species (ROS) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway play critical roles in the pathogenesis of prostate cancer by modulating cell proliferation. Picropodophyllin (PPP), an inhibitor of the insulin-like growth factor 1 receptor (IGF-1R), exerts significant antitumor effects via the PI3K/AKT signaling pathway. However, the effects of PPP on prostate cancer via ROS production and the PI3K/AKT signaling pathway remain elusive. Herein, we focused on examining the antitumor effects of PPP on DU145 and LNCaP human prostate cancer cells to determine the possible molecular mechanism. Our data indicated that the inhibitory effect of PPP on the proliferation of DU145 and LNCaP human prostate cancer cells was mediated by apoptosis induction and cell cycle blockade. Furthermore, PPP significantly influenced the expression of apoptosis-related, cell cycle, ROS production, and PI3K/AKT signaling proteins. These findings suggest that PPP can induce cell cycle arrest and apoptosis via the production of ROS and inhibition of PI3K/AKT signaling pathway, thereby suppressing the proliferation of prostate cancer cells.

Knockdown of miRNA-134-5p rescues dendritic deficits by promoting AMPK-mediated mitophagy in a mouse model of depression.

Neuronal dendrites and dendritic spines are essential for normal synaptic transmission and may be critically involved in the pathophysiology of various neurological disorders, including depression. Emerging data supports the role of mitochondria in dendritic protrusions in modulating the development and morphological plasticity of spines. Mitophagy, a mitochondria-specific form of autophagy, is the fundamental process of clearing damaged mitochondria to maintain cellular homeostasis. As a brain-specific microRNA, miR-134 is localized to the synaptodendritic compartment of hippocampal neurons and negatively regulates the development of dendritic spines. However, the role of miR-134 in mitophagy related to dendritic deficits in the pathophysiology of depression remains unclear. In this study, we showed that miR-134-5p knockdown abrogated depression-like behavioral symptoms and corrected aberrant spine morphology in hippocampal neurons of chronic unpredictable mild stress (CUMS) mice. Moreover, knockdown of miR-134-5p triggered autophagy in dendrites, improved mitochondrial impairment, and induced the generation of autophagosomes in the hippocampus of CUMS mice. We further found that AMP-activated protein kinase (AMPK), which mediates the impairment of defective mitochondria via mitophagy, can bind directly to miR-134-5p and is negatively regulated by this miRNA. This study demonstrates that miR-134-5p exerts an enormous effect on dendritic deficits by promoting AMPK-mediated mitophagy and provides a potential new target for antidepressant drug research and development.

Hydroxyl safflower yellow B combined with doxorubicin inhibits the proliferation of human breast cancer MCF-7 cells.

Doxorubicin (DOX) is currently the preferred chemotherapeutic agent for breast cancer, and hydroxyl safflower yellow B (HSYB) has a tumor growth-inhibiting activity. The present study aimed to investigate the effects of HSYB combined with DOX on the proliferation of human breast cancer MCF-7 cells and explore the underlying mechanism. MTT and cell colony formation assays revealed that the proliferation rate of MCF-7 cells was signifiscantly decreased after HSYB and DOX treatment. Combined HSYB and DOX treatment significantly decreased the expression levels of BCL-2 in MCF-7 cells, while the expression levels of apoptosis-associated proteins, including cleaved caspase-9, BAX and cleaved caspase-3, were markedly increased. Furthermore, flow cytometry and western blot analysis demonstrated that combined HSYB and DOX treatment stimulated an increase in intracellular reactive oxygen species and promoted the release of cytochrome c, leading to apoptosis. The current data suggested that the combination of HSYB and DOX may have marked antitumor activity.