Related Experiment Video
Updated: Aug 7, 2026
10:03
Quantification of Cytokine-Induced Cell Death in Human Colonic Organoids Using Live Fluorescence Microscopy
Published on: August 2, 2024
Cell death induction by isothiocyanates and their underlying molecular mechanisms
Yoshimasa Nakamura1, Noriyuki Miyoshi
1Department of Biofunctional Chemistry, Division of Bioscience, Graduate School of Natural Science and Technology, Okayama University, Okayama, 700-8530, Japan. yossan@cc.okayama-u.ac.jp
Biofactors (Oxford, England)
|July 11, 2006
Summary
Organosulfur compounds like isothiocyanates (ITCs) show chemopreventive properties by inducing apoptosis. Benzyl isothiocyanate (BITC) triggers G2/M cell cycle arrest and apoptosis, particularly in proliferating cells.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Organosulfur compounds, including isothiocyanates (ITCs), are recognized for their chemopreventive potential.
- ITCs have demonstrated the ability to induce apoptosis in various cancer cell lines and in experimental models.
- Understanding the molecular mechanisms of ITC-induced apoptosis is crucial for developing cancer chemoprevention strategies.
Purpose of the Study:
- To elucidate the molecular mechanisms linking cell cycle arrest and apoptosis induced by benzyl isothiocyanate (BITC).
- To investigate the role of specific signaling pathways and molecular intermediates in BITC-mediated cell death.
- To assess the differential cytotoxic effects of BITC on proliferating versus quiescent normal human colon epithelial cells.
Main Methods:
- Utilizing phase-specific synchronized cells to evaluate sensitivity to BITC-induced apoptosis.
- Analyzing gene expression related to G2/M cell cycle arrest.
- Identifying key molecular players, such as phosphorylated Bcl-2, and signaling pathways (p38 MAPK, JNK).
Main Results:
- BITC exposure inhibited G2/M cell cycle progression, correlating with increased expression of G2/M arrest genes and apoptosis induction.
- G2/M phase-arrested cells exhibited higher sensitivity to BITC-induced apoptosis.
- Phosphorylated Bcl-2 was identified as a crucial link between p38 MAPK-dependent cell cycle arrest and JNK activation by BITC.
- BITC preferentially induced cytotoxic effects in proliferating normal human colon epithelial cells compared to quiescent cells.
- Excessive BITC concentrations led to necrotic cell death without DNA ladder formation.
Conclusions:
- BITC effectively induces apoptosis and G2/M cell cycle arrest through specific molecular pathways, including p38 MAPK and JNK signaling.
- The findings highlight the potential of BITC as a chemopreventive agent, with a preference for targeting rapidly dividing cells.
- Understanding these mechanisms provides insights into the biological impact of ITCs on cell death induction in cancer research.
Related Concept Videos
01:30Overview 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 20th century...
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 20th century...
01:00Cellular Injury I: Introduction
Cellular injury occurs when a cell cannot maintain homeostasis or adapt to stressors such as hypoxia, toxins, or trauma. Depending on severity and duration, injury may be reversible, allowing recovery, or irreversible, leading to cell death.General Mechanisms of Cell InjuryAlthough causes vary, most cellular injuries arise from a few key mechanisms that disrupt essential functions and often amplify one another. Cell survival depends on the extent and balance of these disturbances.ATP depletion...
01:11Cellular Injury IlI: Cellular Death
Cell death is the irreversible loss of cellular structure and function, representing the final stage of severe injury. It plays a key role in both normal physiology and disease.Types of Cell DeathThe two main types are necrosis and apoptosis, though others like necroptosis and pyroptosis also exist.Necrosis:Necrosis is an unregulated form of cell death caused by severe injury such as trauma, toxins, or ischemia. It is characterized by cell swelling, membrane loss, rupture, and leakage of...
01:22Cellular 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...
01:17The 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...
01:18Autophagic 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...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...