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Rhaponticin suppresses osteosarcoma through the inhibition of PI3K-Akt-mTOR pathway
Suresh Mickymaray1, Faiz Abdulaziz Alfaiz1, Anand Paramasivam2
1Department of Biology, College of Science, Al-Zulfi, Majmaah University, Riyadh Region, Majmaah 11952, Saudi Arabia.
Abstract:
Osteosarcoma is the frequent pediatric bone cancer where pediatric osteosarcoma incidences are more than 10% within the population. Most of the patients with osteosarcoma fall within the age of 15-30 years. Therefore, in this research, we examined the anticancer effect of Rhaponticin against the human osteosarcoma (MG-63) cells. The cytotoxicity of Rhaponticin on the MC3T3-E1 and MG-63 cells was examined through the MTT assay. The intracellular ROS accumulation, cell nuclear morphological alterations, apoptotic cell death and nuclear damages, and MMP status of Rhaponticin administered MG-63 cells were inspected by fluorescent staining techniques. The cell migration was assessed through scratch assay. The mRNA expressions of PI3K-Akt-mTOR signaling proteins were studied by RT-PCR analysis. Rhaponticin showed potent cytotoxicity, substantially inhibited the MG-63 cell growth, and displayed morphological alterations. However, rhaponticin did not affect the MC3T3-E1 cell viability. Rhaponticin administered MG-63 cells demonstrated augmented intracellular ROS accretion, weakened MMP, increased nuclear damages, and increased apoptosis. Rhaponticin effectively down-regulated the PI3K-Akt-mTOR signaling cascade in the MG-63 cells. These outcomes proved that the Rhaponticin can be a hopeful chemotherapeutic agent in the future to treat human osteosarcoma.
Insights
Rhaponticin demonstrates potent anticancer effects against human osteosarcoma (MG-63) cells by inducing apoptosis and inhibiting growth. This natural compound shows promise as a future chemotherapeutic agent for osteosarcoma treatment.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Osteosarcoma is a prevalent pediatric bone cancer, primarily affecting individuals aged 15-30.
- Current treatments have limitations, necessitating the search for novel therapeutic agents.
Purpose of the Study:
- To investigate the anticancer potential of Rhaponticin against human osteosarcoma (MG-63) cells.
- To elucidate the mechanisms underlying Rhaponticin's effects on osteosarcoma cells.
Main Methods:
- Cytotoxicity assessed via MTT assay on MG-63 and MC3T3-E1 cells.
- Intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), nuclear morphology, and apoptosis evaluated using fluorescent staining.
- Cell migration analyzed by scratch assay.
- mRNA expression of PI3K-Akt-mTOR pathway proteins determined by RT-PCR.
Main Results:
- Rhaponticin exhibited significant cytotoxicity against MG-63 cells while sparing normal MC3T3-E1 cells.
- Treatment led to increased intracellular ROS, apoptosis, and nuclear damage, with decreased MMP.
- Rhaponticin effectively inhibited MG-63 cell migration and down-regulated the PI3K-Akt-mTOR signaling pathway.
Conclusions:
- Rhaponticin possesses potent anti-osteosarcoma properties.
- The compound induces cell death and inhibits growth through ROS generation and PI3K-Akt-mTOR pathway modulation.
- Rhaponticin represents a promising candidate for future osteosarcoma chemotherapy.
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