Rhein Induces Oral Cancer Cell Apoptosis and ROS via Suppresse AKT/mTOR Signaling Pathway In Vitro and In Vivo.

Oral cancer remains the leading cause of death worldwide. Rhein is a natural compound extracted from the traditional Chinese herbal medicine rhubarb, which has demonstrated therapeutic effects in various cancers. However, the specific effects of rhein on oral cancer are still unclear. This study aimed to investigate the potential anticancer activity and underlying mechanisms of rhein in oral cancer cells. The antigrowth effect of rhein in oral cancer cells was estimated by cell proliferation, soft agar colony formation, migration, and invasion assay. The cell cycle and apoptosis were detected by flow cytometry. The underlying mechanism of rhein in oral cancer cells was explored by immunoblotting. The in vivo anticancer effect was evaluated by oral cancer xenografts. Rhein significantly inhibited oral cancer cell growth by inducing apoptosis and S-phase cell cycle arrest. Rhein inhibited oral cancer cell migration and invasion through the regulation of epithelial-mesenchymal transition-related proteins. Rhein induced reactive oxygen species (ROS) accumulation in oral cancer cells to inhibit the AKT/mTOR signaling pathway. Rhein exerted anticancer activity in vitro and in vivo by inducing oral cancer cell apoptosis and ROS via the AKT/mTOR signaling pathway in oral cancer. Rhein is a potential therapeutic drug for oral cancer treatment.

Effects of Sangju Honey on Oral Squamous Carcinoma Cells.

Since ancient times, honey has been used in traditional medicine owing to its pharmacological effects. It possesses anticancer properties. However, the therapeutic implications of Sangju honey in cancer remains unknown. Therefore, we aimed to demonstrate the potential anticancer effects of Sangju honey on human oral squamous cell carcinoma (OSCC), particularly focusing on epithelial-mesenchymal transition (EMT) and apoptotic and mitogen-activated protein kinase (MAPK) signaling pathways. Ca9-22 and YD-10B human OSCC cells were treated with 0.25% or 0.5% Sangju honey, and the cell viability was examined using the Cell Counting Kit-8 assay. Cell morphology studies were conducted to observe morphological changes, and the wound-healing assay was performed to evaluate the proliferation of honey-treated OSCC cells. Western blot analysis was conducted to investigate protein expression related to EMT and apoptotic and MAPK signaling pathways. Sangju honey reduced cell viability, induced morphological changes, and significantly suppressed the proliferation and migration of Ca9-22 and YD-10B cells. The expression of E-cadherin and N-cadherin was increased and decreased, respectively, in both OSCC cell lines. Moreover, Sangju honey stimulated apoptosis by increasing the expression of p21, p53, cleaved caspase 3, and caspase 9. Furthermore, it downregulated the expression of phospho (p)-extracellular signal-regulated kinases 1 and 2, p-c-Jun amino-terminal kinase, and p-p38 in Ca9-22 and YD-10B cells. Sangju honey inhibits Ca9-22 and YD-10B cell proliferation by regulating EMT, inducing apoptosis, and suppressing the MAPK signaling pathway. Thus, it is a potential anticancer agent for human OSCC.

Targeting AKT with costunolide suppresses the growth of colorectal cancer cells and induces apoptosis in vitro and in vivo.

BACKGROUND: Colorectal cancer (CRC) is a clinically challenging malignant tumor worldwide. As a natural product and sesquiterpene lactone, Costunolide (CTD) has been reported to possess anticancer activities. However, the regulation mechanism and precise target of this substance remain undiscovered in CRC. In this study, we found that CTD inhibited CRC cell proliferation in vitro and in vivo by targeting AKT. METHODS: Effects of CTD on colon cancer cell growth in vitro were evaluated in cell proliferation assays, migration and invasion, propidium iodide, and annexin V-staining analyses. Targets of CTD were identified utilizing phosphoprotein-specific antibody array; Costunolide-sepharose conjugated bead pull-down analysis and knockdown techniques. We investigated the underlying mechanisms of CTD by ubiquitination, immunofluorescence staining, and western blot assays. Cell-derived tumour xenografts (CDX) in nude mice and immunohistochemistry were used to assess anti-tumour effects of CTD in vivo. RESULTS: CTD suppressed the proliferation, anchorage-independent colony growth and epithelial-mesenchymal transformation (EMT) of CRC cells including HCT-15, HCT-116 and DLD1. Besides, the CTD also triggered cell apoptosis and cell cycle arrest at the G2/M phase. The CTD activates and induces p53 stability by inhibiting MDM2 ubiquitination via the suppression of AKT's phosphorylation in vitro. The CTD suppresses cell growth in a p53-independent fashion manner; p53 activation may contribute to the anticancer activity of CTD via target AKT. Finally, the CTD decreased the volume of CDX tumors without of the body weight loss and reduced the expression of AKT-MDM2-p53 signaling pathway in xenograft tumors. CONCLUSIONS: Our project has uncovered the mechanism underlying the biological activity of CTD in colon cancer and confirmed the AKT is a directly target of CTD. All of which These results revealed that CTD might be a new AKT inhibitor in colon cancer treatment, and CTD is worthy of further exploration in preclinical and clinical trials.

Anticancer effects and potential mechanisms of ginsenoside Rh2 in various cancer types (Review).

Ginsenoside Rh2 (G­Rh2) is a natural bioactive product derived from Panax ginseng Meyer (P. ginseng). G­Rh2 exhibits anticancer activity in various human cancer cell lines both in vitro and in vivo by modulating several signaling pathways, such as those of PDZ­binding kinase/T­LAK cell­originated protein kinase, phosphatidylinositol 3­kinase, protein kinase B, mammalian target of rapamycin, epidermal growth factor receptor, p53, and reactive oxygen species. Moreover, G­Rh2 could effectively reverse drug resistance and enhance therapeutic effects in cancer therapy. This review summarizes the chemical properties, in vitro and in vivo anticancer activity, and underlying molecular mechanisms of G­Rh2 to facilitate cancer chemoprevention studies.