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.

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.

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
4.3K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.0K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
9.8K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.1K
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
5.6K