Related Experiment Video

Updated: May 15, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

p53 modulates the AMPK inhibitor compound C induced apoptosis in human skin cancer cells

Shi-Wei Huang1, Chun-Ying Wu, Yen-Ting Wang

  • 1Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.

Toxicology and Applied Pharmacology
|January 1, 2013
PubMed

Insights

Compound C induces autophagy and apoptosis in skin cancer cells. Its apoptotic effect is p53-dependent, with wildtype p53 enhancing cell death via DNA damage and p53 target gene activation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Compound C inhibits AMP-activated protein kinase (AMPK), a key energy sensor.
  • Previous studies linked Compound C to apoptosis in various cancer types (myeloma, breast, glioma).
  • The role of Compound C in skin cancer, particularly concerning p53 status, remained unclear.

Purpose of the Study:

  • To investigate the effects of Compound C on skin cancer cell lines.
  • To determine the role of p53 in mediating Compound C's effects on skin cancer cells.
  • To elucidate the molecular mechanisms underlying Compound C-induced cell death and cell cycle arrest.

Main Methods:

  • Treatment of skin cancer cell lines (BCC) with Compound C.
  • Analysis of autophagy and apoptosis induction.
  • Assessment of p53 protein status (upregulation, phosphorylation, nuclear translocation).
  • Investigation of reactive oxygen species (ROS) generation and ATM protein activation.
  • Use of p53-knockdown BCC sublines to assess p53 dependency.
  • Cell cycle analysis (G2/M phase) and Cdc2 expression evaluation.

Main Results:

  • Compound C induced both autophagy and apoptosis in all tested skin cancer cell lines.
  • Apoptosis was more pronounced in p53 wildtype skin cancer cells compared to p53-mutant cells.
  • Compound C activated p53 signaling, including upregulation, phosphorylation, nuclear translocation, and target gene expression, in a p53-dependent manner.
  • p53 activation was linked to Compound C-induced DNA damage, ROS generation, and ATM activation.
  • p53-knockdown cells showed reduced sensitivity to Compound C, with attenuated apoptosis but preserved autophagy.
  • G2/M cell cycle arrest in p53-knockdown cells correlated with sustained inactive Tyr15 phosphor-Cdc2.

Conclusions:

  • Compound C induces apoptosis in skin cancer cells in a p53-dependent manner.
  • p53 status is a critical determinant of sensitivity to Compound C-induced apoptosis.
  • Compound C's mechanism involves p53 activation, DNA damage, and ROS generation, leading to apoptosis and cell cycle arrest.

More Related Videos

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence04:56

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence

Published on: December 30, 2025

Procedure and Key Optimization Strategies for an Automated Capillary Electrophoretic-based Immunoassay Method09:32

Procedure and Key Optimization Strategies for an Automated Capillary Electrophoretic-based Immunoassay Method

Published on: September 10, 2017

Related Concept Videos

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 daughter...
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...
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 rapamycin-insensitive companion...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...