Related Experiment Video

Updated: Jun 9, 2025

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
19:44

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

Published on: May 30, 2012

18.7K

Synthetic Peptides Induce Human Colorectal Cancer Cell Death via Proapoptotic Pathways

Felipe P Mesquita1, Francisco L de Oliveira1, Emerson L da Silva1

  • 1Pharmacogenetics Laboratory, Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza, CE 60430-275, Brazil.

ACS Omega
|October 28, 2024
PubMed

Insights

Antimicrobial peptides PepGAT and PepKAA show promise in treating colorectal cancer (CRC). These peptides induce cancer cell death and inhibit invasion without harming normal cells, offering a potential new strategy against drug-resistant cancers.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Drug and chemotherapy resistance in cancer presents a significant global health challenge.
  • Repurposing antimicrobial peptides (AMPs) offers a promising strategy to overcome cancer resistance.
  • Existing research suggests AMPs possess cytotoxic effects against cancer cells.

Purpose of the Study:

  • To investigate the potential of repurposing antimicrobial peptides PepGAT and PepKAA for cancer treatment.
  • To evaluate the efficacy and mechanisms of action of PepGAT and PepKAA against colorectal cancer (CRC) cells.
  • To assess the safety profile of these peptides in normal human cells.

Main Methods:

  • Screening of PepGAT and PepKAA against various cancer cell lines.
  • Determination of IC50 values for colorectal cancer (CRC) cells.
  • Analysis of cell cycle progression, apoptosis induction (caspase 3/7 assays, flow cytometry, qPCR), reactive oxygen species (ROS) production, and membrane permeabilization.
  • Assessment of cell invasion inhibition.
  • Evaluation of cytotoxicity in normal human cells.

Main Results:

  • PepGAT and PepKAA demonstrated significant cytotoxicity against CRC cells with IC50 values of 125.42 μM and 40.51 μM, respectively.
  • Both peptides induced G2/M cell cycle arrest and apoptosis in HCT-116 cells, confirmed by gene expression modulation and biochemical assays.
  • Peptides caused ROS overaccumulation, increased membrane permeabilization, and inhibited cell invasion.
  • Previous studies confirmed no toxicity to normal human cells.

Conclusions:

  • Antimicrobial peptides PepGAT and PepKAA exhibit potent anticancer activity against colorectal cancer.
  • The mechanism involves induction of apoptosis, cell cycle arrest, ROS generation, and membrane damage.
  • These peptides show potential as novel therapeutic agents for cancer treatment, particularly in overcoming drug resistance, with a favorable safety profile.

More Related Videos

Author Spotlight: Optimization of Ultrashort Peptide Matrices for Colorectal Cancer Organoids10:23

Author Spotlight: Optimization of Ultrashort Peptide Matrices for Colorectal Cancer Organoids

Published on: May 3, 2024

823
Evaluating Cell Death Using Cell-Free Supernatant of Probiotics in Three-Dimensional Spheroid Cultures of Colorectal Cancer Cells06:07

Evaluating Cell Death Using Cell-Free Supernatant of Probiotics in Three-Dimensional Spheroid Cultures of Colorectal Cancer Cells

Published on: June 13, 2020

6.6K

Related Concept Videos

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...
6.3K
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...
6.4K
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
11.2K
Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
7.1K
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...
12.3K
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized...
3.7K