Related Experiment Video

Updated: Sep 13, 2025

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

18.8K

Tempol Induces Oxidative Stress, ER Stress and Apoptosis via MAPK/Akt/mTOR Pathway Suppression in HT29 (Colon) and

Gorkem Ozdemir1, Halil Mahir Kaplan2

  • 1Department of Gastroenterological Surgery, Adana City Training and Research Hospital, 01230 Adana, Turkey.

Current Issues in Molecular Biology
|July 29, 2025
PubMed

Insights

The synthetic antioxidant Tempol effectively combats colon and gastric cancer cells by inducing apoptosis and oxidative stress. It also suppresses key pro-survival signaling pathways, highlighting its therapeutic potential.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Gastric and colon cancers often exhibit dysregulated Mitogen-Activated Protein Kinase (MAPK) and Protein Kinase B/Mammalian Target of Rapamycin (Akt/mTOR) signaling pathways.
  • These pathways contribute significantly to cancer progression and are potential therapeutic targets.

Purpose of the Study:

  • To investigate the anti-cancer potential of Tempol, a synthetic antioxidant, in human colon (HT29) and gastric (CRL-1739) cancer cell lines.
  • To elucidate the mechanisms underlying Tempol's anti-cancer effects, focusing on apoptosis induction and modulation of key signaling pathways.

Main Methods:

  • Treatment of HT29 and CRL-1739 cells with 2 mM Tempol for 48 hours.
  • Evaluation of apoptosis markers (Bax, cleaved caspase-3, Bcl-2), signaling pathway activity (p-ERK, p-JNK, p-AKT, p-mTOR), and stress/apoptosis-related proteins (WEE1, GADD153, GRP78, AIF).
  • Assessment of total oxidant status and total antioxidant status.

Main Results:

  • Tempol significantly increased pro-apoptotic proteins (Bax, cleaved caspase-3) and decreased anti-apoptotic protein (Bcl-2) in both cell lines (p < 0.0001).
  • Tempol markedly reduced the activity of key signaling pathways (p-ERK, p-JNK, p-AKT, p-mTOR) (p < 0.0001).
  • Tempol treatment increased levels of WEE1, GADD153, GRP78, and AIF, alongside increased oxidant status and decreased antioxidant status.

Conclusions:

  • Tempol demonstrates anti-cancer activity through multiple mechanisms, including apoptosis induction and oxidative stress.
  • Tempol effectively suppresses pro-survival signaling pathways implicated in gastric and colon cancer progression.
  • These findings support Tempol's potential as a therapeutic agent for gastric and colon cancers.
Keywords:
Akt/mTOR pathwayCRL-1739HT29MAPK pathwayapoptosiscolon cancergastric cancertempol

More Related Videos

Author Spotlight: Exploring Huotan Jiedu Tongluo Decoction as an Antihypertensive Drug05:57

Author Spotlight: Exploring Huotan Jiedu Tongluo Decoction as an Antihypertensive Drug

Published on: May 17, 2024

848
Protection of H9c2 Myocardial Cells from Oxidative Stress by Crocetin via PINK1/Parkin Pathway-Mediated Mitophagy07:40

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

Published on: May 26, 2023

1.3K

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.9K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.6K
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...
4.0K
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...
15.0K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
6.1K
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...
6.9K