Related Experiment Video

Updated: May 23, 2026

Protection of H9c2 Myocardial Cells from Oxidative Stress by Crocetin via PINK1/Parkin Pathway-Mediated Mitophagy
07:40

Protection of H9c2 Myocardial Cells from Oxidative Stress by Crocetin via PINK1/Parkin Pathway-Mediated Mitophagy

Published on: May 26, 2023

Cucurbitacin induces autophagy through mitochondrial ROS production which counteracts to limit caspase-dependent

Tiejun Zhang1, Yuwen Li, Kyeong Ah Park

  • 1Department of Pharmacology, Research Institute for Medical Science, Infection Signaling Network Research Center, Daejeon Regional Cancer Center, Daejeon, Republic of Korea.

Autophagy
|March 24, 2012
PubMed

Insights

Cucurbitacin triggers cancer cell death via autophagy and reactive oxygen species, independent of STAT3 inhibition. This suggests cucurbitacin as a potential anti-cancer drug by modulating cell death pathways.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Signal transducer and activator of transcription 3 (STAT3) inhibition is a validated cancer therapy strategy.
  • Cucurbitacin is a small molecule STAT3 inhibitor investigated for cancer treatment.
  • Understanding cucurbitacin's precise molecular mechanisms, including its role in autophagy, is crucial for therapeutic development.

Purpose of the Study:

  • To elucidate the molecular mechanisms of cucurbitacin-induced cell death.
  • To investigate the specific involvement of autophagy in cucurbitacin's anti-cancer effects.
  • To determine if cucurbitacin's effects are dependent on STAT3 inhibition.

Main Methods:

  • Treatment of various cancer cell types with cucurbitacin.
  • Assessment of cell death modes (apoptotic vs. non-apoptotic, caspase-dependent vs. independent).
  • Analysis of autophagy markers (LC3-II, autophagosomes) and reactive oxygen species (ROS) production.
  • Inhibition of autophagy using wortmannin or genetic knockdown (Atg5, Beclin 1).
  • Evaluation of signaling pathway activation (ERK, JNK).

Main Results:

  • Cucurbitacin induced non-apoptotic, caspase-independent cell death.
  • Enhanced autophagy, indicated by increased LC3-II conversion and autophagosome accumulation, was observed.
  • Cucurbitacin's effects were independent of STAT3 inhibition but mediated by mitochondrial ROS production, activating ERK and JNK pathways.
  • Autophagy inhibition did not prevent cell death; instead, it shifted the cell death mode to caspase-dependent apoptosis.

Conclusions:

  • Cucurbitacin induces cancer cell death primarily through ROS-mediated autophagy and subsequent ERK/JNK activation, not STAT3 inhibition.
  • Autophagy plays a complex role, with its suppression potentially leading to apoptosis.
  • Cucurbitacin shows promise as an anti-cancer agent by manipulating the balance between autophagic and apoptotic cell death pathways.

More Related Videos

Cell-Based Drug Screening for Inhibitors of Autophagy Related 4B Cysteine Peptidase09:51

Cell-Based Drug Screening for Inhibitors of Autophagy Related 4B Cysteine Peptidase

Published on: June 30, 2023

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 cells.
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
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...
Delivery Pathways to the Lysosome01:36

Delivery Pathways to the Lysosome

Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...