Targeted cancer therapy with natural compounds is more effective than nontargeted therapy. Nobiletin is a flavonoid derived from citrus peel that has anticancer activity. Cluster of differentiation 36 (CD36) is a member of the class B scavenger receptor family that is involved in importing fatty acids into cells. CD36 plays a role in tumor angiogenesis by binding to its ligand, thrombospondin-1 (TSP-1), and then interacting with transforming growth factor beta 1 (TGFβ1). CD36 is implicated in tumor metastasis through its roles in fatty acid metabolism. This study investigated the molecular mechanisms underlying nobiletin’s anticancer activity by characterizing its interactions with CD36 as the target molecule. We hypothesize that the anti-angiogenic activity of nobiletin involving its regulation of CD36 via signal transducer and activator of transcription 3 (STAT3) rather than through TSP-1. Gene analysis identified a Gamma interferon activation site (GAS) element in the CD36 gene promoter that acts as a STAT3 binding site, an interaction that was confirmed by ChIP assay. STAT3 interacts with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), suggesting that nobiletin also acts through the CD36/ (STAT3)/NF-κB signaling axis. Nobiletin inhibited CD36-dependent breast cancer cell migration and invasion as well as CD36-mediated tumor sphere formation. Taken together, these results suggest that nobiletin inhibits cancer stem cells in multiple ways.

The major hallmarks of tumor progression are angiogenesis, migration and metastasis. Among the components of Rhodiola rosea, salidroside (p‑hydroxyphenethyl-β‑d-glucoside) is one of the most potent, and is present in all Rhodiola species. Recent data have revealed the anticancer effects of salidroside; however, the mechanism underlying its ability to inhibit tumor angiogenesis remains unknown. The present study aimed to analyze how salidroside affects major factors involved in breast cancer, and to elucidate its ability to inhibit angiogenesis and invasion. Signal transducer and activator of transcription 3 (STAT3) is a marker for tumor angiogenesis and migration, which interacts with matrix metalloproteinases (MMPs). Specifically, MMPs act as a downstream target for STAT3. Using western blotting and reverse transcription-quantitative polymerase chain reaction analysis, the present study demonstrated that treatment of MDA‑MB 231 triple-negative breast cancer (TNBC) cells with salidroside led to inhibition of invasion and migration markers, and of STAT3 signaling. Furthermore, in vitro angiogenesis analyses in human umbilical vein endothelial cells confirmed the anti-angiogenic activity of salidroside. An electrophoretic mobility shift assay also demonstrated that salidroside may inhibit the DNA-binding activity of STAT3, preventing STAT3 from binding to a novel binding site of the MMP2 gene promoter. In conclusion, the present results demonstrated that salidroside may downregulate the STAT3 signaling pathway, and inhibit cell viability, migration and invasion through MMPs in breast cancer cells.

Background/Aim: Non-small cell lung cancer (NSCLC) is one among the most common cancers worldwide. Recently, dietary phytochemicals have been reported as an attractive approach to improve the symptoms of NSCLC patients. Tannic acid is a natural polyphenol, which is known to have anticancer effects on in vitro models of breast, gingival and colon cancer. However, the molecular mechanisms associated with the actions of tannic acid on A549 human lung cancer cells have not been elucidated. Materials and Methods: In this study, we analyzed the effect of tannic acid on A549 cells and their underlying mechanisms using western blotting, flow cytometry, invasion assay and tumorsphere formation assay. Results: Tannic acid treatment suppressed the viability of A549 cells through cell cycle arrest and induction of the intrinsic pathways of apoptosis. In addition, the various malignant phenotypes of A549 cells including invasion, migration, and stemness were inhibited by tannic acid treatment. Conclusion: Tannic acid could be used as an effective inhibitor of lung cancer progression.

Background/Aim: Colorectal cancer is one of the most common malignancies worldwide. Small moleculebased chemotherapy is an attractive approach for the chemoprevention and treatment of colorectal cancer. Methylsulfonylmethane (MSM) is a natural organosulfur compound with anticancer properties, as revealed by studies on in vitro models of gingival, prostate, lung, hepatic, and breast cancer. However, the molecular mechanisms underlying the effects of MSM in colon cancer cells remain unclear. Materials and Methods: Here, we investigated the effects of MSM, especially on the cell cycle arrest and apoptosis, in HT-29 cells. Results: MSM suppressed the viability of HT-29 cells by inducing apoptosis and cell cycle arrest at the G 0 /G 1 phase. MSM suppressed the sphereforming ability and expression of stemness markers in cells. Conclusion: MSM has anti-cancer effects on HT-29 cells, and induces cell cycle arrest and apoptosis, while suppressing the stemness potential.Colorectal cancer is one of the most commonly diagnosed malignancies worldwide, and its prevalence is increasing in the recent years (1). It is classified on the basis of histopathological features, including the clinical, morphological, and molecular characteristics of the cancer (2).Among the various histopathological types, adenocarcinoma accounts for 95% to 98% of all cases of colorectal cancer (3, 4). Colorectal cancer is usually treated by surgery, radiation therapy, or chemotherapy (5). Among these treatment strategies, chemotherapy can generally be administered either before or after surgery for reducing tumor size and the risk of recurrence ( 6). Chemotherapy may also be administered for providing relief from the symptoms of colorectal cancer in cases where the tumor cannot be removed surgically, or in cases of severe metastasis to other sites of the body (6). Therefore, it is necessary to develop novel chemotherapeutic agents for targeting molecular abnormalities at various stages of malignancies, which requires continuous efforts for the discovery of novel compounds and elucidation of the mechanisms underlying their mode of action.Methylsulfonylmethane (MSM) is a simple organosulfur compound, which is also known as dimethylsulfone, methylsulfone, sulfonyl bis methane, organic sulfur, or crystalline dimethyl sulfoxide (7). MSM occurs naturally in plants, animals, and various natural products (7). It has been recognized as a safe substance, and the US Food and Drug Administration (FDA) classified MSM as an 'Generally Recognized as Safe (GRAS)' grade molecule (8). It has been reported that MSM has numerous physiological functions, and is particularly well-known due to its analgesic properties in chronic pain caused by inflammatory diseases (9).In the recent past, numerous studies have reported the anticancer properties of MSM using in vitro models (10). For instance, it has been reported that MSM induces ER stressmediated apoptosis in HCT116 cells (11). Another study demonstrated the antiproliferative effects of MSM and suggested its inhibitory po...

Background: To understand the athletic characteristics of Thoroughbreds, high-throughput analysis has been conducted using horse muscle tissue. However, an in vitro system has been lacking for studying and validating genes from in silico data. The aim of this study is to validate genes from differentially expressed genes (DEGs) of our previous RNA-sequencing data in vitro. Also, we investigated the effects of exercise-induced stress including heat, oxidative, hypoxic and cortisol stress on horse skeletal muscle derived cells with the top six upregulated genes of DEGs. Methods: Enriched pathway analysis was conducted using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool with upregulated genes in horse skeletal muscle tissue after exercise. Among the candidates, the top six genes were analysed through geneMANIA to investigate gene networks. Muscle cells derived from neonatal horse skeletal tissue were maintained and subjected to exercise-related stressors. Transcriptional changes in the top six genes followed by stressors were investigated using qRT-PCR. Results: The inflammation response pathway was the most commonly upregulated pathway after horse exercise. Under non-cytotoxic conditions of exercise-related stressors, the transcriptional response of the top six genes was different among types of stress. Oxidative stress yielded the most similar expression pattern to DEGs. Conclusion: Our results indicate that transcriptional change after horse exercise in skeletal muscle tissue strongly relates to stress response. qRT-PCR results showed that stressors contribute differently to the transcriptional regulation. These results would be valuable information to understand horse exercise in the stress aspect.