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Updated: Jun 25, 2026

Analytical Determination of Mitochondrial Function of Excised Solid Tumor Homogenates
Published on: August 6, 2021
Suppression of tumor growth in vivo by the mitocan alpha-tocopheryl succinate requires respiratory complex II
Lan-Feng Dong1, Ruth Freeman, Ji Liu
1Apoptosis Research Group and Genomic Research Centre, School of Medical Science, Griffith University, Southport, Queensland, Australia. l.dong@griffith.edu.au
Purpose:
Vitamin E analogues are potent novel anticancer drugs. The purpose of this study was to elucidate the cellular target by which these agents, represented by alpha-tocopoheryl succinate (alpha-TOS), suppress tumors in vivo, with the focus on the mitochondrial complex II (CII).
Experimental Design:
Chinese hamster lung fibroblasts with functional, dysfunctional, and reconstituted CII were transformed using H-Ras. The cells were then used to form xenografts in immunocompromized mice, and response of the cells and the tumors to alpha-TOS was studied.
Results:
The CII-functional and CII-reconstituted cells, unlike their CII-dysfunctional counterparts, responded to alpha-TOS by reactive oxygen species generation and apoptosis execution. Tumors derived from these cell lines reciprocated their responses to alpha-TOS. Thus, growth of CII-functional and CII-reconstituted tumors was strongly suppressed by the agent, and this was accompanied by high level of apoptosis induction in the tumor cells. On the other hand, alpha-TOS did not inhibit the CII-dysfunctional tumors.
Conclusions:
We document in this report a novel paradigm, according to which the mitochondrial CII, which rarely mutates in human neoplasias, is a plausible target for anticancer drugs from the group of vitamin E analogues, providing support for their testing in clinical trials.
Insights
Vitamin E analogues like alpha-tocopheryl succinate (alpha-TOS) show anticancer potential. This study reveals mitochondrial complex II (CII) as a key cellular target for alpha-TOS, demonstrating its effectiveness against tumors with functional CII.
Area of Science:
- Biochemistry
- Oncology
- Mitochondrial Biology
Background:
- Vitamin E analogues, such as alpha-tocopheryl succinate (alpha-TOS), are recognized for their potent anticancer properties.
- Understanding the precise cellular mechanisms and targets of these novel anticancer agents is crucial for their therapeutic development.
Purpose of the Study:
- To identify the specific cellular target of vitamin E analogues, exemplified by alpha-TOS, in suppressing tumor growth in vivo.
- To investigate the role of mitochondrial complex II (CII) as a potential target for alpha-TOS-mediated anticancer effects.
Main Methods:
- Utilized Chinese hamster lung fibroblasts engineered with varying functional states of mitochondrial complex II (CII).
- Transformed cells with H-Ras and established xenografts in immunocompromised mice to study tumor response.
- Assessed the effects of alpha-TOS on cellular reactive oxygen species (ROS) generation, apoptosis, and tumor growth suppression.
Main Results:
- alpha-TOS induced reactive oxygen species (ROS) generation and apoptosis in cells with functional or reconstituted CII.
- Tumors derived from CII-functional and CII-reconstituted cells exhibited significant growth suppression and apoptosis upon alpha-TOS treatment.
- alpha-TOS failed to inhibit tumors originating from CII-dysfunctional cells, highlighting the critical role of CII.
Conclusions:
- Mitochondrial complex II (CII) is identified as a novel and plausible cellular target for anticancer drugs based on vitamin E analogues.
- This finding supports the potential of vitamin E analogues as a new class of anticancer therapeutics.
- The study advocates for the clinical evaluation of vitamin E analogues targeting mitochondrial CII in cancer treatment.
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