(-)-Guaiol Triggers Immunogenic Cell Death and Inhibits Tumor Growth in Non-small Cell Lung Cancer

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 2022 Nov 28

PMID 36441354

Authors

Xiaohui Yang

Junling Yang

Xiaoxia Gu

Yuhua Tao

Hongjuan Ji

Xian Miao

Shuijie Shen

Haiyang Zang

Affiliations

Soon will be listed here.

Abstract

(-)-Guaiol is a sesquiterpenoid found in many traditional Chinese medicines with potent antitumor activity. However, its therapeutic effect and mechanism in non-small cell lung cancer (NSCLC) have not been fully elucidated. In this study, (-)-Guaiol was found to induce immunogenic cell death (ICD) in NSCLC in vitro. Using (-)-Guaiol in vivo, we found that (-)-Guaiol could suppress tumor growth, increase dendritic cell activation, and enhance T-cell infiltration. Vaccination experiments suggest that cellular immunoprophylaxis after (-)-Guaiol intervention can suppress tumor growth. Previous studies have found that (-)-Guaiol induces apoptosis and autophagy in NSCLC. Apoptosis and autophagy are closely related to ICD. To explore whether autophagy and apoptosis are involved in (-)-Guaiol-induced ICD, we used inhibitors of apoptosis and autophagy. The results showed that the release of damage-associated molecular patterns (DAMPs) was partly reversed after inhibition of apoptosis and autophagy. In conclusion, these results suggested that the (-)-Guaiol triggers immunogenic cell death and inhibits tumor growth in NSCLC.

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References

Liang W, Liu J, He J . Driving the Improvement of Lung Cancer Prognosis. Cancer Cell. 2020; 38(4):449-451. DOI: 10.1016/j.ccell.2020.09.008. View

Zappa C, Mousa S . Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res. 2016; 5(3):288-300. PMC: 4931124. DOI: 10.21037/tlcr.2016.06.07. View

Morris L, Chan T . Lung Cancer Evolution: What's Immunity Got to Do with It?. Cancer Cell. 2019; 35(5):711-713. DOI: 10.1016/j.ccell.2019.04.009. View

Shu Z, Pu J, Chen L, Zhang Y, Rahman K, Qin L . Alisma orientale: Ethnopharmacology, Phytochemistry and Pharmacology of an Important Traditional Chinese Medicine. Am J Chin Med. 2016; 44(2):227-51. DOI: 10.1142/S0192415X16500142. View

Pereira D, Amparo T, Almeida T, Costa F, Brandao G, Dos Santos O . Cytotoxic activity of butanolic extract from L. flowers and vehiculated in micelles in bladder cancer cells and fibroblasts. Nat Prod Res. 2020; 36(4):1100-1104. DOI: 10.1080/14786419.2020.1851220. View

Choudhary M, Batool I, Atif M, Hussain S, Atta-Ur-Rahman . Microbial transformation of (-)-guaiol and antibacterial activity of its transformed products. J Nat Prod. 2007; 70(5):849-52. DOI: 10.1021/np068052a. View

Winnett V, Sirdaarta J, White A, Clarke F, Cock I . Inhibition of Klebsiella pneumoniae growth by selected Australian plants: natural approaches for the prevention and management of ankylosing spondylitis. Inflammopharmacology. 2017; 25(2):223-235. DOI: 10.1007/s10787-017-0328-1. View

Park H, Choi S, Baek N, Kim S, Eun J, Yang J . Guaiane sesquiterpenoids from Torilis japonica and their cytotoxic effects on human cancer cell lines. Arch Pharm Res. 2006; 29(2):131-4. DOI: 10.1007/BF02974273. View

Ratnayake R, Covell D, Ransom T, Gustafson K, Beutler J . Englerin A, a selective inhibitor of renal cancer cell growth, from Phyllanthus engleri. Org Lett. 2008; 11(1):57-60. PMC: 2651161. DOI: 10.1021/ol802339w. View

10.

Gao S, Wang G, Huang Z, Lei X, Bian Y, Liu Y . Selection of Reference Genes for qRT-PCR Analysis in after Hot-Air Drying. Molecules. 2019; 24(1). PMC: 6337709. DOI: 10.3390/molecules24010136. View

11.

Yang Q, Wu J, Luo Y, Huang N, Zhen N, Zhou Y . (-)-Guaiol regulates RAD51 stability via autophagy to induce cell apoptosis in non-small cell lung cancer. Oncotarget. 2016; 7(38):62585-62597. PMC: 5308748. DOI: 10.18632/oncotarget.11540. View

12.

Yang X, Zhu J, Wu J, Huang N, Cui Z, Luo Y . (-)-Guaiol regulates autophagic cell death depending on mTOR signaling in NSCLC. Cancer Biol Ther. 2018; 19(8):706-714. PMC: 6067839. DOI: 10.1080/15384047.2018.1451277. View

13.

Galluzzi L, Buque A, Kepp O, Zitvogel L, Kroemer G . Immunogenic cell death in cancer and infectious disease. Nat Rev Immunol. 2016; 17(2):97-111. DOI: 10.1038/nri.2016.107. View

14.

Asadzadeh Z, Safarzadeh E, Safaei S, Baradaran A, Mohammadi A, Hajiasgharzadeh K . Current Approaches for Combination Therapy of Cancer: The Role of Immunogenic Cell Death. Cancers (Basel). 2020; 12(4). PMC: 7226590. DOI: 10.3390/cancers12041047. View

15.

Krysko D, Garg A, Kaczmarek A, Krysko O, Agostinis P, Vandenabeele P . Immunogenic cell death and DAMPs in cancer therapy. Nat Rev Cancer. 2012; 12(12):860-75. DOI: 10.1038/nrc3380. View

16.

Masse D, Ebstein F, Bougras G, Harb J, Meflah K, Gregoire M . Increased expression of inducible HSP70 in apoptotic cells is correlated with their efficacy for antitumor vaccine therapy. Int J Cancer. 2004; 111(4):575-83. DOI: 10.1002/ijc.20249. View

17.

Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A . Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med. 2007; 13(9):1050-9. DOI: 10.1038/nm1622. View

18.

Martins I, Wang Y, Michaud M, Ma Y, Sukkurwala A, Shen S . Molecular mechanisms of ATP secretion during immunogenic cell death. Cell Death Differ. 2013; 21(1):79-91. PMC: 3857631. DOI: 10.1038/cdd.2013.75. View

19.

Zhou J, Wang G, Chen Y, Wang H, Hua Y, Cai Z . Immunogenic cell death in cancer therapy: Present and emerging inducers. J Cell Mol Med. 2019; 23(8):4854-4865. PMC: 6653385. DOI: 10.1111/jcmm.14356. View

20.

Vanmeerbeek I, Sprooten J, De Ruysscher D, Tejpar S, Vandenberghe P, Fucikova J . Trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology. Oncoimmunology. 2020; 9(1):1703449. PMC: 6959434. DOI: 10.1080/2162402X.2019.1703449. View