Inhibitory effects of Actinidia Chinensis planch root extracts (acRoots) on human lung cancer cells through retinoic acid receptor beta
Accepted: 9 September 2017
Published: 9 September 2017
Actinidia Chinensis Planch roots (acRoots) are used to treat many cancers, although the anti-tumor mechanism by which acRoots inhibit cancer cell growth remains unclear. The present study aims at investigating inhibitory effects of acRoots on human lung cancer cells and potential mechanisms. Our data demonstrate that the inhibitory effects of acRoots on lung cancer cells depend on genetic backgrounds and phenotypes of cells. We furthermore found the expression of metabolism-associated gene profiles varied between acRoots-hypersensitive (H460) or hyposensitive lung cancer cells (H1299) after screening lung cancer cells with different genetic backgrounds. We selected retinoic acid receptor beta (RARB) as the core target within metabolism-associated core gene networks and evaluated RARB changes and roles in cells treated with acRoots at different concentrations and timeframes. Hypersensitive cancer cells with the deletion of RARB expression did not response to the treatment with acRoots, while RARB deletion did not change effects of acRoots on hyposensitive cells. Thus, it seems that RARB as the core target within metabolism-associated networks plays important roles in the regulation of lung cancer cell sensitivity to acRoots.
2. Chang J, Case R. Cytotoxic phenolic constituents from the root of Actinidia chinensis. Planta Medica 2005; 71: 955-9.
3. Huo J, Qin F, Cai X, Ju J, Hu C, Wang Z, Lu W, Wang X, Cao P. Chinese medicine formula "Weikang Keli" induces autophagic cell death on human gastric cancer cell line SGC-7901. Phytomedicine. 2013 Jan 15;20(2):159-65.
4. Fang T, Hou J, He M, Wang L, Zheng M, Wang X, Xia J. Actinidia chinensis Planch root extract (acRoots) inhibits hepatocellular carcinoma progression by inhibiting EP3 expression. Cell Biol Toxicol. 2016 Dec;32(6):499-511.
5. Chiang HC, Wang CH, Yeh SC, Lin YH, Kuo YT, Liao CW, et al. Comparative microarray analyses of mono(2-ethylhexyl)phthalate impacts on fat cell bioenergetics and adipokine network. Cell Biol Toxicol. 2017 Jan 12. doi: 10.1007/s10565-016-9380-7. [PMID: 28083810]
6. Song WY, Xu GH, Zhang GJ. [Effect of Actinidia chinensis planch polysaccharide on the growth and apoptosis, and p-p38 expression in human gastric cancer SGC-7901 cells]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2014 Mar;34(3):329-33.
7. Li W, Liu Y, Zeng S, Xiao G, Wang G, Wang Y, Peng M, Huang H. Gene Expression Profiling of Development and Anthocyanin Accumulation in Kiwifruit (Actinidia chinensis) Based on Transcriptome Sequencing. PLoS One. 2015 Aug 24;10(8):e0136439.
8. He M, Hou J, Wang L, Zheng M, Fang T, Wang X, Xia J. Actinidia chinensis Planch root extract inhibits cholesterol metabolism in hepatocellular carcinoma through upregulation of PCSK9. Oncotarget. 2017 Jun 27;8(26):42136-42148.
9. Cheng CY, Su SC, Chen CH, Chen WL, Deng ST, Chung WH. HLA associations and clinical implications in T-cell mediated drug hypersensitivity reactions: an updated review. J Immunol Res. 2014;2014:565320.
10. Pirmohamed M, Ostrov DA, Park BK. New genetic findings lead the way to a better understanding of fundamental mechanisms of drug hypersensitivity. J Allergy Clin Immunol. 2015 Aug;136(2):236-44.
11. di Masi A, Leboffe L, De Marinis E, Pagano F, Cicconi L, Rochette-Egly C, Lo-Coco F, Ascenzi P, Nervi C. Retinoic acid receptors: from molecular mechanisms to cancer therapy. Mol Aspects Med. 2015 Feb;41:1-115.
12. Connolly RM, Nguyen NK, Sukumar S. Molecular pathways: current role and future directions of the retinoic acid pathway in cancer prevention and treatment. Clin Cancer Res. 2013 Apr 1;19(7):1651-9.
13. Brabender J, Metzger R, Salonga D, Danenberg KD, Danenberg PV, Hölscher AH, Schneider PM. Comprehensive expression analysis of retinoic acid receptors and retinoid X receptors in non-small cell lung cancer: implications for tumor development and prognosis. Carcinogenesis. 2005 Mar;26(3):525-30.
14. Marchwicka A, Cunningham A, Marcinkowska E, Brown G. Therapeutic use of selective synthetic ligands for retinoic acid receptors: a patent review. Expert Opin Ther Pat. 2016 Aug;26(8):957-71.
15. Yu XT, Zeng T, Wang XD, Li GJ, Chen LN. Unravelling personalized dysfunctional gene network of complex diseases based on differential network model. J Transl Med. 2015 Jun 13;13:189.
16. Lu J, Wang W, Xu M, Li Y, Chen C, Wang X. A global view of regulatory networks in lung cancer: An approach to understand homogeneity and heterogeneity. Semin Cancer Biol. 2017 Feb;42:31-38.
17. Chen K, Li Y, Xu H, Zhang C, Li Z, Wang W, Wang B. An analysis of the gene interaction networks identifying the role of PARP1 in metastasis of non-small cell lung cancer. Gene. 2017 Aug 23. pii: S0378-1119(17)30648-0.
18. Kettunen E, Hernandez-Vargas H, Cros MP, Durand G, Le Calvez-Kelm F, Stuopelyte K, et al. Asbestos-associated genome-wide DNA methylation changes in lung cancer. Int J Cancer. 2017 Jul 19.
19. Pearce EJ, Everts B. Dendritic cell metabolism. Nat Rev Immunol. 2015 Jan;15(1):18-29. doi: 10.1038/nri3771.
20. Osanai M, Lee GH. The retinoic acid-metabolizing enzyme CYP26A1 upregulates fascin and promotes the malignant behavior of breast carcinoma cells. Oncol Rep. 2015 Aug;34(2):850-8.
21. Wang X. New biomarkers and therapeutics can be discovered during COPD-lung cancer transition. Cell Biol Toxicol. 2016 Oct;32(5):359-61.
22. Chen C, Shi L, Li Y, Wang X, Yang S. Disease-specific dynamic biomarkers selected by integrating inflammatory mediators with clinical informatics in ARDS patients with severe pneumonia. Cell Biol Toxicol. 2016 Jun;32(3):169-84.
23. Shi L, Zhu B, Xu M, Wang X. Selection of AECOPD-specific immunomodulatory biomarkers by integrating genomics and proteomics with clinical informatics. Cell Biol Toxicol. 2017 Aug 4. doi: 10.1007/s10565-017-9405-x. PMID: 28779230
24. Wang L, Zhu B, Zhang M, Wang X. Roles of immune microenvironment heterogeneity in therapy-associated biomarkers in lung cancer. Semin Cell Dev Biol. 2017 Apr;64:90-97.
25. Wang XD. New biomarkers and therapeutics can be discovered during COPD-lung cancer transition. Cell Biol Toxicol. 2016 Oct;32(5):359-61
26. Niu F, Wang DC, Lu JP, Wu W, Wang XD. Potentials of single-cell biology in identification and validation of disease biomarkers. J Cell Mol Med. 2016 Sep;20(9):1789-95