Imperatorin exhibits anticancer activities in human colon cancer cells via the caspase cascade

Yi Mei Zheng1, Amy Xiaoxu Lu2, James Zheng Shen2

  • 1College of Biological Science and Technology, Minnan Normal University, Zhangzhou, Fujian 363000, P.R. China.

Oncology Reports
|January 23, 2016
PubMed

Insights

Imperatorin, a compound from Angelica dahurica, shows significant anti-cancer effects against colon cancer cells. It effectively inhibits proliferation and induces apoptosis, highlighting its potential as a novel colon cancer therapeutic agent.

Area of Science:

  • Pharmacology
  • Oncology
  • Natural Products Chemistry

Background:

  • Colon cancer remains a leading cause of cancer mortality, necessitating novel therapeutic strategies.
  • Imperatorin, derived from Angelica dahurica, has traditional uses but its anti-cancer properties require elucidation.
  • Existing colon cancer treatments have limitations, creating a need for alternative agents.

Purpose of the Study:

  • To investigate the anti-proliferative and apoptosis-inducing effects of imperatorin on HT-29 colon cancer cells.
  • To determine the mechanism by which imperatorin affects colon cancer cell growth.
  • To evaluate the potential of imperatorin as a colon cancer therapeutic agent.

Main Methods:

  • Cell culture of HT-29 colon cancer cell line.
  • Treatment with varying concentrations of imperatorin.
  • Assessment of cell proliferation using IC50 values.
  • Analysis of apoptosis induction via p53 and caspase cascade.
  • Cell cycle analysis to determine phase arrest.

Main Results:

  • Imperatorin significantly inhibited HT-29 colon cancer cell growth with an IC50 of 78 µM.
  • Imperatorin induced apoptosis through the upregulation of p53 and activation of the caspase cascade.
  • Cell cycle analysis revealed that imperatorin caused arrest in the G1 phase.
  • A dose-dependent increase in the apoptotic index was observed with increasing imperatorin concentrations.

Conclusions:

  • Imperatorin exhibits significant anti-proliferative activity against colon cancer cells.
  • Imperatorin promotes colon cancer cell apoptosis and G1 cell cycle arrest.
  • Imperatorin demonstrates potential as a promising natural anticancer agent for colon cancer treatment.

Related Concept Videos

Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
14.5K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
9.2K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
9.3K
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

5.6K
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...
6.2K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
6.3K