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Updated: Feb 15, 2026

A Flow Cytometry-Based Cytotoxicity Assay for the Assessment of Human NK Cell Activity
Published on: August 9, 2017
Flavones and Aminoflavones Increase the Cytotoxicity of NK Cells in Human Non-Small Cell Lung Cancer
Ping-Chih Hsu1,2, Chih-Cheng Chien3, Yang-Je Cheng4
1Division of Thoracic Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
Abstract:
Natural flavonoids (flavones) and synthetic aminoflavones are known for their anti-cancer properties; however, their immunomodulation ability has been largely unexplored. This study determined that synthetic flavones and aminoflavones modulate the cytotoxicity of natural killer (NK) cells against lung cancer cells. Notably, flavones 2, 3, and 6 and aminoflavone 8 were shown to increase the cytotoxicity of NK-92MI cells against A549 lung cancer cells without adversely affecting MRC5 normal cells. Aminoflavone 8 enhanced NK-92MI cell cytotoxicity, as evidenced by the elevated expression of cytotoxic effectors, such as IFN-γ, perforin, and granzyme B. Aminoflavone 8 also inhibited STAT3 phosphorylation in A549 lung cancer and NK-92MI cells under co-culture conditions. Moreover, aminoflavone 8 exhibited anti-tumour effects in a lung cancer xenograft mouse model. Combined therapy with aminoflavone 8 and NK-92MI cells had synergistic anti-tumour effects without liver or kidney toxicity. Our analysis revealed that the amino group in the C6 position of aminoflavone 8 was crucial to the enhanced cytotoxicity of NK cells. These findings suggest that aminoflavone 8 can potentiate NK cell cytotoxicity against lung cancer cells, highlighting its potential as a novel therapeutic agent for the treatment of lung cancer.
Insights
Synthetic aminoflavone 8 boosts natural killer (NK) cell anti-cancer activity against lung cancer. This compound enhances NK cell effectiveness and shows promise as a novel lung cancer therapy.
Area of Science:
- Immunology
- Pharmacology
- Oncology
Background:
- Flavonoids and aminoflavones possess anti-cancer properties.
- Their immunomodulatory effects, particularly on natural killer (NK) cells, are underexplored.
- Understanding these interactions is crucial for novel cancer therapies.
Purpose of the Study:
- To investigate the immunomodulatory effects of synthetic flavones and aminoflavones on NK cell cytotoxicity against lung cancer.
- To evaluate the therapeutic potential of aminoflavone 8 in preclinical lung cancer models.
Main Methods:
- Assessed NK-92MI cell cytotoxicity against A549 lung cancer cells and MRC5 normal cells.
- Measured expression of cytotoxic effectors (IFN-γ, perforin, granzyme B) and STAT3 phosphorylation.
- Evaluated anti-tumour effects of aminoflavone 8 in a lung cancer xenograft mouse model.
Main Results:
- Flavones 2, 3, 6 and aminoflavone 8 increased NK cell cytotoxicity against lung cancer cells without harming normal cells.
- Aminoflavone 8 significantly enhanced NK cell effector molecule expression and inhibited STAT3 phosphorylation.
- Combined aminoflavone 8 and NK-92MI cell therapy demonstrated synergistic anti-tumour effects in vivo with no observed liver or kidney toxicity.
Conclusions:
- Aminoflavone 8 effectively potentiates NK cell-mediated cytotoxicity against lung cancer.
- The C6 amino group is critical for aminoflavone 8's enhanced NK cell activity.
- Aminoflavone 8 represents a promising novel therapeutic agent for lung cancer treatment.
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