Related Experiment Video

Updated: Oct 4, 2026

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

Augmented adriamycin sensitivity in cells transduced with an antisense tumor necrosis factor gene is mediated by

M Sasaki1, D Kobayashi, N Watanabe

  • 1Division of Laboratory Diagnosis, Sapporo Medical University School of Medicine, South-1 West-16, Chuo-ku, Sapporo 060-0061, Japan.

Japanese Journal of Cancer Research : Gann
|September 27, 2001
PubMed

Insights

Introducing an antisense tumor necrosis factor (TNF) gene sequence enhances adriamycin (ADM) effectiveness in pancreatic cancer cells. This occurs through increased reactive oxygen species (ROS) production and subsequent caspase-3 activation, improving ADM sensitivity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Adriamycin (ADM) resistance is a significant challenge in pancreatic cancer treatment.
  • Antisense tumor necrosis factor (TNF) gene transduction can enhance ADM cytotoxicity.
  • The precise signal transduction pathway affected by antisense TNF in ADM-treated cells is not fully understood.

Purpose of the Study:

  • To elucidate the role of reactive oxygen species (ROS) and caspase-3 in ADM-induced cytotoxicity in pancreatic cancer cells with antisense TNF gene transduction.
  • To investigate the mechanism by which antisense TNF enhances ADM sensitivity.

Main Methods:

  • Utilized ADM-resistant pancreatic carcinoma (PANC-1) cells.
  • Administered N-acetyl-L-cysteine (NAC) as an antioxidant and Ac-DMQD-CHO as a caspase-3 inhibitor.
  • Created stable antisense-TNF transfectants and compared them with mock transfectants and parent cells.
  • Measured ADM-induced cytotoxicity, ROS production, and caspase-3 activity.

Main Results:

  • Both NAC and Ac-DMQD-CHO inhibited ADM-induced cytotoxicity in PANC-1 cells.
  • NAC suppressed ADM-induced caspase-3 activity, while Ac-DMQD-CHO did not affect ROS levels.
  • Antisense-TNF transfectants exhibited increased ADM sensitivity, ROS production, and caspase-3 activity compared to controls.
  • Caspase-3 activity was found to be downstream of ROS production.

Conclusions:

  • Increased caspase-3 activity, downstream of ROS production, is a key mechanism enhancing ADM sensitivity in pancreatic cancer cells via antisense TNF gene transduction.
  • This study provides insights into overcoming ADM resistance in pancreatic cancer.

More Related Videos

Establishing Cell Lines Overexpressing DR3 to Assess the Apoptotic Response to Anti-mitotic Therapeutics12:28

Establishing Cell Lines Overexpressing DR3 to Assess the Apoptotic Response to Anti-mitotic Therapeutics

Published on: January 11, 2019

Detecting Anastasis In Vivo by CaspaseTracker Biosensor20:16

Detecting Anastasis In Vivo by CaspaseTracker Biosensor

Published on: February 1, 2018

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.
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...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...