In recent years, the concept of combined therapy using gold hybrid nanomaterials has been broadly adopted to pioneer new anticancer treatments. However, their synergistic anticancer effects have yet to be thoroughly investigated. Herein,a hybrid gold nanobipyramid nanostructure coated with molybdenum disulfide (MoS2) semiconductor (AuNBPs@MoS2) was proposed as a smart nanozyme for anticancer therapy and two-photon bioimaging. The hybrid material showed dramatically enhanced localized surface plasmon resonance property under excitation owing to its anisotropic nature, coupled with the rich electron density in MoS2, resulting in the superior in situ photogeneration of reactive oxidative species (ROS - 1O2, •OH). We demonstrated that the synergistic effect of enhanced photothermal conversion and generation of ROS could increase the anticancer effect of AuNBPs@MoS2. Two-photon luminescence imaging confirmed that AuNBPs@MoS2 was successfully internalized in cancer cells and that simultaneous anticancer treatments based on catalytic and photothermal therapy could be achieved. This study highlighted, for the first time, a novel approach of plasmon-mediated powerful anticancer therapy and imaging via the unprecedented combination of anisotropic AuNBPs and two-dimensional MoS2 material.

Fisetin (3,3-,4-,7-tetrahydroxyflavone), a naturally occurring flavonoid, has antioxidant, anti-inflammatory, and anticancer effects. Oral squamous cell carcinoma (OSCC) has a 5-year survival rate lower than that of most other carcinomas, and can create functional and aesthetic problems for the patient. New therapies for OSCC are necessary, and treatment using plant-derived natural substances has recently become a trend. It has been suggested that autophagy may play an important role in cancer therapy. Several studies demonstrated that autophagy inhibition enhances apoptotic cell death. Therefore, autophagy inhibition might be a promising therapeutic method against OSCC. Our results showed that fisetin induced apoptotic cell death in human tongue squamous cell line Ca9-22 could be enhanced by inhibition of autophagy. Thus, autophagy process in fisetin treated OSCC might presumed to play a role of pro-survival. The combination of fisetin and an effective autophagy inhibitor could be a potentially adjuvant and useful treatment for oral cancer.

Delphinidin is major anthocyanidin that is extracted from many pigmented fruits and vegetables. This substance has anti‐oxidant, anti‐inflammatory, anti‐angiogenic, and anti‐cancer properties. In addition, delphinidin strongly suppresses the migration and invasion of various cancer cells during tumorigenesis. Although delphinidin has anti‐cancer effects, little is known about its functional roles in osteosarcoma (OS). For these reasons, we have demonstrated the effects of delphinidin on OS cell lines. The effects of delphinidin on cell viability and growth of OS cells were assessed using the MTT assay and colony formation assays. Hoechst staining indicated that the delphinidin‐treated OS cells were undergoing apoptosis. Flow cytometry, confocal microscopy, and a western blot analysis also indicated evidence of apoptosis. Inhibition of cell migration and invasion was found to be associated with epithelial‐to‐mesenchymal transition (EMT), observed by using a wound healing assay, an invasion assay, and a western blot analysis. Furthermore, delphinidin treatment resulted in a profound reduction of phosphorylated forms of ERK and p38. These findings demonstrate that delphinidin treatment suppressed EMT through the mitogen‐activated protein kinase (MAPK) signaling pathway in OS cell lines. Taken together, our results suggest that delphinidin strongly inhibits cell proliferation and induces apoptosis. Delphinidin treatment also suppresses cell migration and prevents EMT via the MAPK‐signaling pathway in OS cell lines. For these reasons, delphinidin has anti‐cancer effects and can suppress metastasis in OS cell lines, and it might be worth using as an OS therapeutic agent.

Mangosteen has long been used as a traditional medicine and is known to have antibacterial, antioxidant, and anticancer effects. Although the effects of α-mangostin, a natural compound extracted from the pericarp of mangosteen, have been investigated in many studies, there is limited data on the effects of the compound in human oral squamous cell carcinoma (OSCC). In this study, α-mangostin was assessed as a potential anticancer agent against human OSCC cells. α-Mangostin inhibited cell proliferation and induced cell death in OSCC cells in a dose- and time-dependent manner with little to no effect on normal human PDLF cells. α-Mangostin treatment clearly showed apoptotic evidences such as nuclear fragmentation and accumulation of annexin V and PI-positive cells on OSCC cells. α-Mangostin treatment also caused the collapse of mitochondrial membrane potential and the translocation of cytochrome c from the mitochondria into the cytosol. The expressions of the mitochondria-related proteins were activated by α-mangostin. Treatment with α-mangostin also induced G1 phase arrest and downregulated cell cycle-related proteins (CDK/cyclin). Hence, α-mangostin specifically induces cell death and inhibits proliferation in OSCC cells via the intrinsic apoptosis pathway and cell cycle arrest at the G1 phase, suggesting that α-mangostin may be an effective agent for the treatment of OSCC.

Embelin is an active ingredient of traditional herbal remedies for cancer and other diseases.Recently, it has been suggested that autophagy may play an important role in cancer therapy.However, little data are available regarding the role of autophagy in oral cancers. Therefore, we conducted this study to examine whether Embelin modulates autophagy in Ca9-22. Our results showed that Embelin had anticancer activity against the Ca9-22 human tongue squamous cell, and we observed that autophagic vacuoles were formed by MDC and AO. We also analyzed Embelintreated Ca9-22 cells for the presence of biochemical markers and found that it directly affected the conversion of LC3-II, the degradation of p62/SQSTM1, full-length cleavage formation of ATG5-ATG12 complex and Beline-1, and caspase activation. Rescue experiments using an autophagy inhibitor showed Embelin-induced cell death in Ca9-22, confirming that autophagy acts as a pro-death signal. Furthermore, Embelin exhibited anticancer activity against Ca9-22 via both autophagy and apoptosis. These findings suggest that Embelin may potentially contribute to oral cancer treatment and provide useful information for the development of a new therapeutic agent. K E Y W O R D Sapoptosis, autophagy, embelin, oral squamous cell carcinoma, XIAP inhibitor