Related Experiment Video

Updated: Jun 14, 2026

Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells
15:53

Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells

Published on: August 21, 2013

p66Shc is indispensable for phenethyl isothiocyanate-induced apoptosis in human prostate cancer cells

Dong Xiao1, Shivendra V Singh

  • 1Department of Pharmacology and Chemical Biology, and University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.

Cancer Research
|April 1, 2010
PubMed

Insights

Phenethyl isothiocyanate (PEITC) induces cancer cell death through apoptosis, a process dependent on the growth factor adapter protein p66(Shc). This protein

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Death Pathways

Background:

  • Phenethyl isothiocyanate (PEITC) is a natural compound that selectively inhibits cancer cell growth.
  • The precise mechanism by which PEITC induces apoptosis remains incompletely understood.

Purpose of the Study:

  • To elucidate the role of growth factor adapter protein p66(Shc) in PEITC-induced apoptosis.
  • To investigate the molecular mechanisms linking PEITC treatment, p66(Shc) activation, and cell death in prostate cancer.

Main Methods:

  • Utilized p66(Shc) knockout mouse embryonic fibroblasts and prostate cancer cell lines (PC-3, LNCaP).
  • Assessed apoptosis via DNA fragmentation and caspase-3 activation assays.
  • Investigated p66(Shc) phosphorylation, binding with Pin1, and mitochondrial translocation using Western blotting and immunofluorescence.
  • Evaluated PEITC efficacy in vivo using tumor xenograft models in mice.

Main Results:

  • p66(Shc) knockout cells showed resistance to PEITC-induced growth inhibition and apoptosis.
  • PEITC treatment increased p66(Shc) phosphorylation at Ser(36) and its binding with Pin1 in cancer cells.
  • Knockdown of p66(Shc) protected cells against PEITC-induced DNA fragmentation and reactive oxygen species production.
  • PEITC induced p66(Shc) translocation to mitochondria and demonstrated in vivo anti-tumor activity.

Conclusions:

  • p66(Shc) is essential for PEITC-mediated apoptosis in human prostate cancer cells.
  • PEITC's mechanism involves p66(Shc) phosphorylation, Pin1 interaction, and mitochondrial translocation.
  • These findings highlight p66(Shc) as a key regulator in PEITC-induced cancer cell death.

More Related Videos

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen19:44

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

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

Related Concept Videos

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...
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...
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...
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.
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.