Oridonin enhances cytotoxic activity of natural killer cells against lung cancer

Tsong-Long Hwang; Chuan-Hsin Chang

doi:10.1016/j.intimp.2023.110669

Oridonin enhances cytotoxic activity of natural killer cells against lung cancer

Int Immunopharmacol. 2023 Sep:122:110669. doi: 10.1016/j.intimp.2023.110669. Epub 2023 Jul 20.

Authors

Tsong-Long Hwang¹, Chuan-Hsin Chang²

Affiliations

¹ Research Center for Chinese Herbal Medicine, Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan; Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; Department of Chemical Engineering, Ming Chi University of Technology, New Taipei City, 243, Taiwan. Electronic address: htl@mail.cgu.edu.tw.
² Research Center for Chinese Herbal Medicine, Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan. Electronic address: chuanhsin@mail.cgust.edu.tw.

PMID: 37480753
DOI: 10.1016/j.intimp.2023.110669

Abstract

Background: Oridonin is a Chinese herbal medicine exhibiting anti-tumor properties; however, its immune modulation capacity has yet to be elucidated. Our objective in this study was to determine whether oridonin enhances the anti-tumor activity of natural killer (NK) cells against lung cancer cells.

Methods: LDH-releasing assays were used to investigate the effects of oridonin on NK-92MI cell activity against lung cancer cells. Flow cytometry and real-time PCR were used to examine the effects of oridonin on degranulation markers, cytotoxic factors, activating receptors on NK-92MI cells, and ligands in lung cancer cells. Western blot analysis provided insight into the mechanisms underlying the observed effects.

Results: Oridonin enhanced the cytotoxic effects of NK-92MI cells against A549 lung cancer cells. This effect involved upregulating the expression of the degranulation marker CD107a and IFN-γ as well as activating receptors on NK cells and their ligand MICA/B. Oridonin also inhibited STAT3 phosphorylation in A549 cells and NK-92MI cells. A lung cancer mouse model confirmed the anti-tumor effects of oridonin and NK-92MI cells, wherein both treatments alone suppressed tumor growth. Oridonin was also shown to have a synergistic effect on the anti-tumor activity of NK-92MI cells.

Conclusions: The ability of oridonin to enhance the cytotoxic effects of NK cells indicates its potential as a novel therapeutic agent for the treatment of lung cancer.

Keywords: Anticancer effect; Lung cancer; Natural killer cell; Oridonin.

MeSH terms

Animals
Antineoplastic Agents* / pharmacology
Antineoplastic Agents* / therapeutic use
Diterpenes, Kaurane* / pharmacology
Diterpenes, Kaurane* / therapeutic use
Killer Cells, Natural
Lung Neoplasms* / drug therapy
Mice

Substances

oridonin
Antineoplastic Agents
Diterpenes, Kaurane