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

Abstract

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.

Dieckol, a natural polyphenolic drug, inhibits the proliferation and migration of colon cancer cells by inhibiting PI3K, AKT, and mTOR phosphorylation

“…Later, 32 and 50 μg/ml of DKL and 0.5 μg/ml of PTX were given to HCT‐116 cells and continued for another 24 h. After that, each well received 10 μl of DCFH‐DA stain, which was left to sit for an hour. After treatment, ROS levels in the HCT‐116 cells were observed under a fluorescence microscope [ 25,26 ] , or rhodamine‐123 for the evaluation of ΔΨ m by exploratory investigation under the inverted fluorescence microscope.…”

Stylopine: A potential natural metabolite to block vascular endothelial growth factor receptor 2 (VEGFR2) in osteosarcoma therapy

“… Liu et al (2017) reported that apatinib as a highly selective VEGFR2 antagonist which, has a promising antitumoral effect by the growth inhibition of osteosarcoma cells in vitro and in vivo through apoptosis, cell cycle arrest, and autophagy ( Liu et al, 2017 ). Zhang et al (2021) evaluated that the effective inhibition of dieckol in the PI3K/AKT/mTOR signaling on the MG-63 cells ( Zhang et al, 2021 ).…”

“… Bahuguna et al (2017) reported that MTT assay for cytotoxicity evaluation has many advantages in especially its effectiveness and simplicity, which make it more suitable to assess the anti-cancer potential of any test samples at preliminary levels ( Bahuguna et al, 2017 ). Zhang et al (2021) demonstrated the cytotoxic effect of dieckol in human osteosarcoma MG-63 cells using MTT assay ( Zhang et al, 2021 ). Liu et al (2015) revealed that the combination of ZD6474 and celecoxib had a stronger antiproliferative effect in human osteosarcoma cells (MG-63) through MTT assay ( Liu et al, 2015 ).…”

Evaluation on Hepatoprotection of Dihydromyricetin in Acetaminophen-Induced Hepatotoxicity Based on Analysis of Inflammation and Apoptosis Mediated by PI3K/AKT Pathway

“…Bcl-2 and Bax were the downstream target proteins of the PI3K/AKT signaling pathway. 25 To further explore the relationship between apoptosis and liver damage induced by APAP, western blot analysis was performed to assess the expression levels of Bcl-2 and Bax. We found that the PI3K/ AKT pathway APAP-induced liver injury was successfully inhibited after 7 days of DHM pretreatment, and the protein levels of Bax and Bcl-2 were close to that of the control group.…”