Raddeanin A exerts potent efficacy against non-small cell lung cancer by inhibiting cyclin-dependent kinase 6

Xian Wang1, Xiao Lin2, Yuxin Liu2

  • 1Pulmonary Division, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325035, China; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Shanghai Fengxian District Central Hospital, No. 6600, Nanfeng Highway, Fengxian District, Shanghai 201499, China.

Translational Oncology
|April 11, 2025
PubMed
Abstract

Insights

Raddeanin A effectively inhibits non-small cell lung cancer (NSCLC) growth by halting cell cycle progression. This natural compound shows promise as a novel therapeutic agent for NSCLC treatment.

Area of Science:

  • Pharmacology
  • Oncology
  • Molecular Biology

Background:

  • Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide.
  • Developing novel therapeutic agents with improved efficacy and reduced toxicity is crucial for effective NSCLC treatment.

Purpose of the Study:

  • To investigate the anti-tumor effects and underlying mechanisms of Raddeanin A in NSCLC.
  • To evaluate the efficacy of Raddeanin A both in vitro and in vivo.

Main Methods:

  • Assessed Raddeanin A's effects on NSCLC cell cycle, proliferation, migration, and invasion using flow cytometry and cell biological assays.
  • Employed network pharmacology, molecular docking, molecular dynamics, SPR, Co-IP, and immunofluorescence to identify Raddeanin A's molecular targets.
  • Evaluated in vivo anti-tumor effects using a nude mouse xenograft tumor model.

Main Results:

  • Raddeanin A significantly inhibited NSCLC cell survival, invasion, and migration, inducing G1 phase cell cycle arrest.
  • Identified Cyclin-Dependent Kinase 6 (CDK6) as a key target, with Raddeanin A demonstrating tight binding and inhibition of CDK6.
  • Confirmed Raddeanin A's inhibitory effect on NSCLC tumor growth in a preclinical in vivo model.

Conclusions:

  • Raddeanin A effectively blocks the G1 phase cell cycle by inhibiting CDK6.
  • Raddeanin A exhibits significant anti-tumor activity against NSCLC, positioning it as a potential novel therapeutic agent.

Related Concept Videos

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...
4.6K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.0K
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
5.2K
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.5K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.4K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.1K