The inhibitory effect of CTAB on human osteosarcoma through the PI3K/AKT signaling pathway

Wacili Da1, Lin Tao1, Yue Zhu1

  • 1Department of Orthopedics, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.

Insights

Cetrimonium bromide (CTAB) shows promise as a novel osteosarcoma treatment. This compound effectively inhibits cancer cell proliferation, migration, and invasion while promoting apoptosis, with minimal toxicity observed in vivo.

Area of Science:

  • Oncology
  • Pharmacology
  • Biochemistry

Background:

  • Osteosarcoma (OS) presents significant clinical challenges due to metastasis, recurrence, and multidrug resistance.
  • There is a critical need for novel, effective, and low-toxicity therapeutic agents for osteosarcoma treatment.

Purpose of the Study:

  • To investigate the anti-cancer effects of cetrimonium bromide (CTAB) on osteosarcoma cells.
  • To elucidate the underlying molecular mechanisms of CTAB's action in osteosarcoma.

Main Methods:

  • In vitro studies assessed CTAB's impact on osteosarcoma cell proliferation, cell cycle, migration, and invasion.
  • Caspase-mediated apoptosis and mitochondrial toxicity were evaluated.
  • In vivo studies examined CTAB's efficacy and organ toxicity in a preclinical osteosarcoma model.

Main Results:

  • CTAB inhibited osteosarcoma cell proliferation, migration, and invasion in a dose- and time-dependent manner.
  • CTAB induced G1 phase cell cycle arrest and promoted caspase-mediated apoptosis via the PI3K/AKT pathway.
  • CTAB demonstrated significant anti-tumor activity in vivo without inducing observable organ toxicity, despite noted mitochondrial toxicity in vitro.

Conclusions:

  • Cetrimonium bromide exhibits significant anti-osteosarcoma properties by inhibiting proliferation and metastasis and inducing apoptosis.
  • The PI3K/AKT signaling pathway is implicated in CTAB's mechanism of action.
  • CTAB represents a potential therapeutic candidate for osteosarcoma treatment.

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
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
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
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.3K
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
2.1K