Cytotoxic Effects of Castalin Nanoparticles Against Osteosarcoma.

The size-dependent bioactivities of castalin were analyzed by comparing the cytotoxic effects of native castalin and castalin nanoparticles on osteosarcoma in vitro and in vivo. In vitro experiments indicated that castalin nanoparticles induced apoptosis of an osteosarcoma cell line more efficiently than native castalin. The more potent effects of castalin nanoparticles, relative to native castalin, were confirmed in vivo using a xenograft osteosarcoma model. Caco-2 cell transport studies showed that permeation of castalin nanoparticles was higher than native castalin. The higher bioactivity and superior bioavailability of castalin nanoparticles could potentially be utilised to develop novel therapies for osteosarcoma.

Rational Design of a Triple Tumor Microenvironment-Responsive Nanoplatform for Enhanced Tumor Theranostics.

The development of responsive nanoplatforms based on the tumor microenvironment (TME) is critical for tumor diagnosis and treatment. Concentrating on a single TME-responsive nanoplatform, however, may result in insufficient diagnostic accuracy and treatment efficacy. Herein, layered double-hydroxides (LDHs) and rare earth nanomaterials (Er@Lu) were combined to create a triple TME-responsive nanoplatform that was then modified with cypate (a fluorescent dye with strong absorbance) by a peptide chain and loaded with epigallocatechin gallate (EGCG), a chemotherapeutic drug. Multiple responses to TME occurred when Er@Lu/LDH-EGCG reached the colorectal tumor region. Based on an acidic TME, the nanoplatform cracked and released Ni2+ and EGCG. NiS, which was produced by the reaction of Ni2+ with abundant H2 S in tumor cells, was used for photothermal therapy and the released EGCG was used for chemotherapy. The MMP-7 enzyme specifically expressed in tumor cells recognized and cut the peptide chain, resulting in cypate release. The fluorescence of the Er@Lu was then restored along with the release of cypate because of the absorption competition disappearance. Compared to a single TME response, Er@Lu/LDH-EGCG with a triple TME response led to a better synergistic therapeutic effect in vitro and in vivo. This work has provided new approaches for developing multiple TME-responsive therapeutic nanoplatforms for synergistic therapy with improved diagnosis and therapeutic efficiency.

Dieckol exerts anticancer activity in human osteosarcoma (MG-63) cells through the inhibition of PI3K/AKT/mTOR signaling pathway.

BACKGROUND: Osteosarcoma (OS) is the most common malignant bone cancer with more metastasis and increased occurrence in children and teen-agers and being responsible for more number of morbidity and mortality worldwide. OBJECTIVE: The current exploration was planned study the in vitro anticancer actions of dieckol against human OS MG-63 cells via PI3K/AKT/mTOR signaling inhibition. METHODOLOGY: The cytotoxicity of dieckol was scrutinized by MTT assay. Effects of dieckol on the ROS accumulation, apoptotic cell death, and MMP level in the MG-63 cells were studied by respective fluorescence staining assays. The levels of proliferative, inflammatory, and apoptotic markers in the dieckol treated MG-63 cells were scrutinized by marker specific kits. The expressions of PI3K, AKT, and mTOR was assayed by RT-PCR. RESULTS: The MTT assay revealed that the dieckol dose dependently prevented MG-63 cells viability and the IC50 was found at 15 µM. Dieckol treatment effectively reduced the MMP level and improved the ROS generation and apoptosis in MG-63 cells. Dieckol also regulated the proliferative (cyclin D1), inflammatory (COX-2, IL-6, TNF-α, and NF-κB), and apoptotic (caspase-3, Bax, Bcl-2) markers in the MG-63 cells. The PI3K/AKT/mTOR signaling in the MG-63 cells were effectively inhibited by the dieckol treatment. CONCLUSION: In conclusion, our findings from this study recommends that the dieckol could be a talented anticancer candidate for the OS management in the future.

CT45A1 promotes the metastasis of osteosarcoma cells in vitro and in vivo through ß-catenin.

Increased expression of cancer/testis antigens (CTAs) is reported in various tumors. However, the unique role of CTAs in tumor genesis has not yet been verified. Here, we first report the functional role of CT45A1 in the carcinogenesis of osteosarcoma. RNA sequencing and immunohistochemistry confirmed that elevated expression of CT45A1 was detected in osteosarcoma, especially in metastatic tissues of osteosarcoma. Furthermore, osteosarcoma patients with poorer prognosis showed high expression of CT45A1. In cell tests, CT45A1 overexpression was shown to strengthen the proliferation, migration, and invasion abilities of osteosarcoma cells, while silencing CT45A1 markedly elicited the opposite effects in these tests by disrupting the activation of ß-catenin. In summary, we identify a novel role of CT45A1 in osteosarcoma. Furthermore, our results suggested that CT45A1 may contribute to the development of osteosarcoma and could be a possible therapeutic target for osteosarcoma patients.

Serum amyloid A promotes osteosarcoma invasion via upregulating αvß3 integrin.

Serum amyloid A (SAA) is regarded as an important acute phase protein involved in tumor progression and metastasis. However, at present there is no evidence of its involvement in osteosarcoma. The present study aimed to investigate the effect of SAA on the invasion of osteosarcoma cells. The effects of SAA on the migration and invasion of osteosarcoma cells were detected using scratch wound healing and transwell assays, respectively. The expression of αvß3 integrin was detected at the protein and mRNA levels in U2OS cells. Agonists, inhibitors or siRNA of formyl peptide receptor like­1 (FPRL­1), mitogen­activated protein kinases and αvß3 integrin were used to investigate the mechanism underlying the effects of SAA on the regulation of U2OS cell migration and invasion. The present study revealed that SAA promoted osteosarcoma cell migration and invasion. SAA upregulated the expression of αvß3 integrin in a concentration­ and time­dependent manner. When inhibiting αvß3 integrin with its antagonist, the migration and invasion abilities of the U2OS cells were markedly inhibited. SAA­induced αvß3 integrin production was significantly downregulated by inhibiting FPRL­1 with siRNA and inhibitors. The present study also found that extracellular signal­regulated kinase (ERK) 1/2, but not c­Jun N­terminal kinase or p38, was important in this process. These findings demonstrated that SAA regulated osteosarcoma cell migration and invasion via the FPRL­1/ERK/αvß3 integrin pathway.