Related Experiment Video

Updated: Oct 2, 2026

Multiomics Analysis of TMEM200A as a Pan-Cancer Biomarker
07:47

Multiomics Analysis of TMEM200A as a Pan-Cancer Biomarker

Published on: September 15, 2023

Gamma-tocopheryl quinone stimulates apoptosis in drug-sensitive and multidrug-resistant cancer cells

Kenneth H Jones1, Jennifer J Liu, Jennifer S Roehm

  • 1Department of Anatomy and Medical Education, The Ohio State University College of Medicine, Columbus 43210, USA. jones.4@osu.edu

Lipids
|March 23, 2002
PubMed

Insights

Arylating gamma-tocopheryl quinones (TQ) demonstrate potent anticancer activity by inducing apoptosis in various cancer cells, including multidrug-resistant (MDR) lines. These compounds offer a promising therapeutic strategy against resistant cancers.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Multidrug resistance (MDR) in cancer is often linked to impaired apoptosis.
  • Tocopheryl quinones (TQ) are derivatives of vitamin E with potential cytotoxic properties.

Purpose of the Study:

  • To investigate the cytotoxic effects and apoptosis-inducing potential of different TQ classes on various human cancer cell lines.
  • To evaluate the efficacy of arylating gamma-TQ against MDR cancer cells expressing P-glycoprotein and MRP proteins.

Main Methods:

  • Cell viability assays, plasma membrane integrity tests, and apoptosis assays (TEM, TUNEL, DNA gel electrophoresis) were performed.
  • Kinetic studies and analysis of apoptosis markers like cytochrome c release and PARP cleavage were conducted.
  • Cytotoxicity was compared to doxorubicin in MRP-expressing cells.

Main Results:

  • Arylating gamma- and delta-TQ, but not alpha-TQ or tocopherols, exhibited significant cytotoxicity and stimulated apoptosis in multiple cancer cell lines.
  • Gamma-TQ demonstrated concentration and time-dependent effects, including loss of membrane integrity and reduced viable cell number.
  • Gamma-TQ's cytotoxicity surpassed doxorubicin in HL60/MX2 cells, and it induced key apoptotic events like cytochrome c release and PARP cleavage.

Conclusions:

  • Arylating TQ, particularly gamma-TQ, are potent cytotoxic agents that effectively induce apoptosis in diverse cancer cell lines.
  • Gamma-TQ overcomes MDR mechanisms mediated by P-glycoprotein and MRP, showing promise for treating resistant cancers.
  • The cytotoxic and apoptosis-stimulating properties of arylating TQ are linked to their electrophilic nature and may have broader therapeutic implications.

Related Concept Videos

Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
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...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
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...