Issue
Chlorogenic-induced inhibition of non-small cancer cells occurs through regulation of histone deacetylase 6
Corresponding Author(s) : Yingping Liang
Cellular and Molecular Biology,
Vol. 64 No. 10: Issue 10
Abstract
Chlorogenic acid (CGA), an ester with various pharmacological effects, is important in cancer therapy. However, the specific antitumor mechanism of CGA is not entirely clear, especially with respect to its suppression of non-small cell lung cancer (NSCLC). The present study was carried out to assess the effect of CGA on NSCLC, and the mechanism involved. Cell viability assay and colony formation assay revealed that CGA blocked the proliferative capacity of NSCLC cells in vitro. Results from the migration assay suggested that CGA also inhibited the migration of A549 cells. Other assays further revealed that CGA strongly and selectively inhibited histone deacetylase 6 (HDAC6) activity and suppressed the activity of matrix metalloproteinase-2 (MMP-2) through decreased expression of Ac-NF-κB. Tumorigenicity assay showed that CGA also inhibited the proliferation and metabolism of NSCLC in vivo. These results indicate that CGA significantly suppresses the proliferation of NSCLC by regulating the activity of histone deacetylase 6.
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- Higuchi M, Owada Y, Inoue T, Watanabe Y, Yamaura T, Fukuhara M, et al. FDG-PET in the evaluation of response to nivolumab in recurrent non-small-cell lung cancer. World J Surg Oncol 2016; 14: 238.
- Wang Y, Xu L, Jiang L. miR-1271 promotes non-small-cell lung cancer cell proliferation and invasion via targeting HOXA5. Biochem Biophys Res Commun 2015; 458: 714-719.
- Sun W, Yuan X, Tian Y, Wu H, Xu H, Hu G, et al. Non-invasive approaches to monitor EGFR-TKI treatment in non-small-cell lung cancer. J Hematol Oncol 2015; 8: 95.
- Haghgoo SM, Allameh A, Mortaz E, Garssen J, Folkerts G, Barnes PJ, et al. Pharmacogenomics and targeted therapy of cancer: Focusing on non-small cell lung cancer. Eur J Pharmacol 2015; 754: 82-91.
- Mistry HB. On the relationship between tumour growth rate and survival in non-small cell lung cancer. Peer J 2017; 5: 4111.
- Lei Z, Xu G, Wang L, Yang H, Liu X, Zhao J, et al. MiR-142-3p represses TGF-beta-induced growth inhibition through repression of TGFbetaR1 in non-small cell lung cancer. Faseb J 2014; 28: 2696-2704.
- Jiang Z, Hao Y, Ding X, Zhang Z, Liu P, Wei X, et al. The effects and mechanisms of SLC34A2 on tumorigenicity in human non-small cell lung cancer stem cells. Tumour Biol 2016; 37: 10383-10392.
- Gao X, Zhao H, Diao C, Wang X, Xie Y, Liu Y, et al. miR-455-3p serves as prognostic factor and regulates the proliferation and migration of non-small cell lung cancer through targeting HOXB5. Biochem Biophys Res Commun 2018; 495: 1074-1080.
- Tian C, Li J, Ren L, Peng R, Chen B, Lin Y. MicroRNA-381 serves as a prognostic factor and inhibits migration and invasion in non-small cell lung cancer by targeting LRH-1. Oncol Rep 2017; 38: 3071-3077.
- Wu WH, Kang Z, Ouyang DS. Progresses in the pharmacology of chlorogenic acid. Nat Prod Res Dev 2006; 18: 691-694.
- Upadhyay R, Mohan Rao LJ. An outlook on chlorogenic acids-occurrence, chemistry, technology, and biological activities. Crit Rev Food Sci Nutr 2013; 53: 968-984.
- Yan Y, Li J, Han J, Hou N, Song Y, Dong L. Chlorogenic acid enhances the effects of 5-fluorouracil in human hepatocellular carcinoma cells through the inhibition of extracellular signal-regulated kinases. Anticancer Drugs 2015; 26: 540-546.
- Naso LG, Valcarcel M, Roura-Ferrer M, Kortazar D, Salado C, Lezama L, et al. Promising antioxidant and anticancer (human breast cancer) oxidovanadium(IV) complex of chlorogenic acid. Synthesis, characterization and spectroscopic examination on the transport mechanism with bovine serum albumin. J Inorg Biochem 2014; 135: 86-99.
- Zhao Y, Wang J, Ballevre O, Luo H, Zhang W. Antihypertensive effects and mechanisms of chlorogenic acids. Hypertens Res 2012; 35: 370.
- Zhu J, Yang Y, Liu S, et al. Anticancer effect of thalidomide in vitro on human osteosarcoma cells. Oncol Rep 2016; 36: 3545.
- Tao R, Wang ZF, Qiu W, He YF, Yan WQ, Sun WY, et al. Role of S100A3 in human hepatocellular carcinoma and the anticancer effect of sodium cantharidinate. Exp Ther Med 2017; 13: 2812-2818.
- Horibe Y, Adachi S, Yasuda I, Yamauchi T, Kawaguchi J, Kozawa O, et al. Anticancer effect of arsenite on cell migration, cell cycle and apoptosis in human pancreatic cancer cells. Oncol Lett 2016; 12: 177-182.
- Xiong WD, Gong J, Xing C. Ferruginol exhibits anticancer effects in OVCAR"‘3 human ovary cancer cells by inducing apoptosis, inhibition of cancer cell migration and G2/M phase cell cycle arrest. Mol Med Report 2017; 16: 7013-7017.
- Luo J, Hu YL, Wang H. Ursolic acid inhibits breast cancer growth by inhibiting proliferation, inducing autophagy and apoptosis, and suppressing inflammatory responses via the PI3K/AKT and NF-kappaB signaling pathways in vitro. Exp Ther Med 2017; 14: 3623-3631.
- Heltweg B, Trapp J, Jung M. In vitro assays for the determination of histone deacetylase activity. Methods 2005; 36: 332-337.
- Wegener D, Wirsching F, Riester D, Schwienhorst A. A fluorogenic histone deacetylase assay well suited for high-throughput activity screening. Chem Biol. 2003; 10: 61-68.
- Szymanski W, Ourailidou ME, Velema WA, Dekker FJ, Feringa BL. Light-Controlled Histone Deacetylase (HDAC) Inhibitors: Towards Photopharmacological Chemotherapy. Chem 2015; 21: 16517-16524.
- Zhang RX, Li Y, Tian DD, Liu Y, Nian W, Zou X, et al. Ursolic acid inhibits proliferation and induces apoptosis by inactivating Wnt/beta-catenin signaling in human osteosarcoma cells. Int J Oncol 2016; 49: 1973-1982.
- Kim DH, Sung B, Kim JA, Kang YJ, Hwang SY, Hwang NL, et al. HS-1793, a resveratrol analogue, downregulates the expression of hypoxia-induced HIF-1 and VEGF and inhibits tumor growth of human breast cancer cells in a nude mouse xenograft model. Int J Oncol 2017; 51: 715.
- Yang CJ, Liu YP, Dai HY, Shiue YL, Tsai CJ, Huang MS, et al. Nuclear HDAC6 inhibits invasion by suppressing NF-kappaB/MMP2 and is inversely correlated with metastasis of non-small cell lung cancer. Oncotarget 2015; 6: 30263-30276.
- T S, T U. Genetic and epigenetic alterations in carcinogenesis. Mutat Res Rev Mutat Res 2000; 462: 235-246.
- Röpke M, Boltze C, Neumann HW, Roessner A, Schneider-Stock R. Genetic and epigenetic alterations in tumor progression in a dedifferentiated chondrosarcoma. Pathol Res Pract 2003; 199: 437-444.
- Kim JA, Yeom YI. Metabolic Signaling to Epigenetic Alterations in Cancer. Biomol Ther 2018; 26: 69-80.
- Gradilone SA, Radtke BN, Bogert PS, Huang BQ, Gajdos GB, Larusso NF. HDAC6 inhibition restores ciliary expression and decreases tumor growth. Cancer Res 2013; 73: 2259-2270.
- Seidel C, Schnekenburger M, Dicato M, Diederich M. Histone deacetylase 6 in health and disease. Epigenomics 2015; 7: 103-118.
- Wang L, Xiang S, Williams KA, Dong H, Bai W, Nicosia SV, et al. Depletion of HDAC6 enhances cisplatin-induced DNA damage and apoptosis in non-small cell lung cancer cells. Plos One 2012; 7: 44265.
- Yang MH, Laurent G, Bause AS, Spang R, German N, Haigis MC, et al. HDAC6 and SIRT2 regulate the acetylation state and oncogenic activity of mutant K-RAS. Mol Cancer Res 2013; 11: 1072-1077.
- Lernoux M, Schnekenburger M, Dicato M, Diederich M. Anti-cancer effects of naturally derived compounds targeting histone deacetylase 6-related pathways. Pharmacological Res 2017;129: 337-356.
- Santanagálvez J, Cisneroszevallos L, Jacobovelázquez DA. Chlorogenic Acid: Recent Advances on Its Dual Role as a Food Additive and a Nutraceutical against Metabolic Syndrome. Molecules 2017; 22: 358.
- Tajik N, Tajik M, Mack I, Enck P. The potential effects of chlorogenic acid, the main phenolic components in coffee, on health: a comprehensive review of the literature. Eur J Nutr. 2017: 1-30.
- Deka SJ, Gorai S, Manna D, Trivedi V. Evidence of PKC Binding and Translocation to explain the anticancer mechanism of chlorogenic acid in breast cancer cells. Curr Mol Med 2017; 17: 79-89.
- Gong L, Wu D, Zou J, Chen J, Chen L, Chen Y, et al. Prognostic impact of serum and tissue MMP-9 in non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget 2016; 7: 18458.
- Wu A, Li J, Wu K, Mo Y, Luo Y, Ye H, et al. LATS2 as a poor prognostic marker regulates non-small cell lung cancer invasion by modulating MMPs expression. Biomed Pharmacother 2016; 82: 290-297.
- Roach DM, Fitridge RA, Laws PE, Millard SH, Varelias A, Cowled PA. Up-regulation of MMP-2 and MMP-9 leads to degradation of type IV collagen during skeletal muscle reperfusion injury; protection by the MMP inhibitor, doxycycline. Eur J Vasc Endovasc Surg 2002; 23: 260-269.
- Pacifico F, Leonardi A. NF-κB in solid tumors. Biochem Pharmacol 2006; 72: 1142-1152.
- Li F, Zhang J, Arfuso F, Chinnathambi A, Zayed ME, Alharbi SA, et al. NF-κB in cancer therapy. Arch Toxicol 2015; 89: 1-21.
References
Higuchi M, Owada Y, Inoue T, Watanabe Y, Yamaura T, Fukuhara M, et al. FDG-PET in the evaluation of response to nivolumab in recurrent non-small-cell lung cancer. World J Surg Oncol 2016; 14: 238.
Wang Y, Xu L, Jiang L. miR-1271 promotes non-small-cell lung cancer cell proliferation and invasion via targeting HOXA5. Biochem Biophys Res Commun 2015; 458: 714-719.
Sun W, Yuan X, Tian Y, Wu H, Xu H, Hu G, et al. Non-invasive approaches to monitor EGFR-TKI treatment in non-small-cell lung cancer. J Hematol Oncol 2015; 8: 95.
Haghgoo SM, Allameh A, Mortaz E, Garssen J, Folkerts G, Barnes PJ, et al. Pharmacogenomics and targeted therapy of cancer: Focusing on non-small cell lung cancer. Eur J Pharmacol 2015; 754: 82-91.
Mistry HB. On the relationship between tumour growth rate and survival in non-small cell lung cancer. Peer J 2017; 5: 4111.
Lei Z, Xu G, Wang L, Yang H, Liu X, Zhao J, et al. MiR-142-3p represses TGF-beta-induced growth inhibition through repression of TGFbetaR1 in non-small cell lung cancer. Faseb J 2014; 28: 2696-2704.
Jiang Z, Hao Y, Ding X, Zhang Z, Liu P, Wei X, et al. The effects and mechanisms of SLC34A2 on tumorigenicity in human non-small cell lung cancer stem cells. Tumour Biol 2016; 37: 10383-10392.
Gao X, Zhao H, Diao C, Wang X, Xie Y, Liu Y, et al. miR-455-3p serves as prognostic factor and regulates the proliferation and migration of non-small cell lung cancer through targeting HOXB5. Biochem Biophys Res Commun 2018; 495: 1074-1080.
Tian C, Li J, Ren L, Peng R, Chen B, Lin Y. MicroRNA-381 serves as a prognostic factor and inhibits migration and invasion in non-small cell lung cancer by targeting LRH-1. Oncol Rep 2017; 38: 3071-3077.
Wu WH, Kang Z, Ouyang DS. Progresses in the pharmacology of chlorogenic acid. Nat Prod Res Dev 2006; 18: 691-694.
Upadhyay R, Mohan Rao LJ. An outlook on chlorogenic acids-occurrence, chemistry, technology, and biological activities. Crit Rev Food Sci Nutr 2013; 53: 968-984.
Yan Y, Li J, Han J, Hou N, Song Y, Dong L. Chlorogenic acid enhances the effects of 5-fluorouracil in human hepatocellular carcinoma cells through the inhibition of extracellular signal-regulated kinases. Anticancer Drugs 2015; 26: 540-546.
Naso LG, Valcarcel M, Roura-Ferrer M, Kortazar D, Salado C, Lezama L, et al. Promising antioxidant and anticancer (human breast cancer) oxidovanadium(IV) complex of chlorogenic acid. Synthesis, characterization and spectroscopic examination on the transport mechanism with bovine serum albumin. J Inorg Biochem 2014; 135: 86-99.
Zhao Y, Wang J, Ballevre O, Luo H, Zhang W. Antihypertensive effects and mechanisms of chlorogenic acids. Hypertens Res 2012; 35: 370.
Zhu J, Yang Y, Liu S, et al. Anticancer effect of thalidomide in vitro on human osteosarcoma cells. Oncol Rep 2016; 36: 3545.
Tao R, Wang ZF, Qiu W, He YF, Yan WQ, Sun WY, et al. Role of S100A3 in human hepatocellular carcinoma and the anticancer effect of sodium cantharidinate. Exp Ther Med 2017; 13: 2812-2818.
Horibe Y, Adachi S, Yasuda I, Yamauchi T, Kawaguchi J, Kozawa O, et al. Anticancer effect of arsenite on cell migration, cell cycle and apoptosis in human pancreatic cancer cells. Oncol Lett 2016; 12: 177-182.
Xiong WD, Gong J, Xing C. Ferruginol exhibits anticancer effects in OVCAR"‘3 human ovary cancer cells by inducing apoptosis, inhibition of cancer cell migration and G2/M phase cell cycle arrest. Mol Med Report 2017; 16: 7013-7017.
Luo J, Hu YL, Wang H. Ursolic acid inhibits breast cancer growth by inhibiting proliferation, inducing autophagy and apoptosis, and suppressing inflammatory responses via the PI3K/AKT and NF-kappaB signaling pathways in vitro. Exp Ther Med 2017; 14: 3623-3631.
Heltweg B, Trapp J, Jung M. In vitro assays for the determination of histone deacetylase activity. Methods 2005; 36: 332-337.
Wegener D, Wirsching F, Riester D, Schwienhorst A. A fluorogenic histone deacetylase assay well suited for high-throughput activity screening. Chem Biol. 2003; 10: 61-68.
Szymanski W, Ourailidou ME, Velema WA, Dekker FJ, Feringa BL. Light-Controlled Histone Deacetylase (HDAC) Inhibitors: Towards Photopharmacological Chemotherapy. Chem 2015; 21: 16517-16524.
Zhang RX, Li Y, Tian DD, Liu Y, Nian W, Zou X, et al. Ursolic acid inhibits proliferation and induces apoptosis by inactivating Wnt/beta-catenin signaling in human osteosarcoma cells. Int J Oncol 2016; 49: 1973-1982.
Kim DH, Sung B, Kim JA, Kang YJ, Hwang SY, Hwang NL, et al. HS-1793, a resveratrol analogue, downregulates the expression of hypoxia-induced HIF-1 and VEGF and inhibits tumor growth of human breast cancer cells in a nude mouse xenograft model. Int J Oncol 2017; 51: 715.
Yang CJ, Liu YP, Dai HY, Shiue YL, Tsai CJ, Huang MS, et al. Nuclear HDAC6 inhibits invasion by suppressing NF-kappaB/MMP2 and is inversely correlated with metastasis of non-small cell lung cancer. Oncotarget 2015; 6: 30263-30276.
T S, T U. Genetic and epigenetic alterations in carcinogenesis. Mutat Res Rev Mutat Res 2000; 462: 235-246.
Röpke M, Boltze C, Neumann HW, Roessner A, Schneider-Stock R. Genetic and epigenetic alterations in tumor progression in a dedifferentiated chondrosarcoma. Pathol Res Pract 2003; 199: 437-444.
Kim JA, Yeom YI. Metabolic Signaling to Epigenetic Alterations in Cancer. Biomol Ther 2018; 26: 69-80.
Gradilone SA, Radtke BN, Bogert PS, Huang BQ, Gajdos GB, Larusso NF. HDAC6 inhibition restores ciliary expression and decreases tumor growth. Cancer Res 2013; 73: 2259-2270.
Seidel C, Schnekenburger M, Dicato M, Diederich M. Histone deacetylase 6 in health and disease. Epigenomics 2015; 7: 103-118.
Wang L, Xiang S, Williams KA, Dong H, Bai W, Nicosia SV, et al. Depletion of HDAC6 enhances cisplatin-induced DNA damage and apoptosis in non-small cell lung cancer cells. Plos One 2012; 7: 44265.
Yang MH, Laurent G, Bause AS, Spang R, German N, Haigis MC, et al. HDAC6 and SIRT2 regulate the acetylation state and oncogenic activity of mutant K-RAS. Mol Cancer Res 2013; 11: 1072-1077.
Lernoux M, Schnekenburger M, Dicato M, Diederich M. Anti-cancer effects of naturally derived compounds targeting histone deacetylase 6-related pathways. Pharmacological Res 2017;129: 337-356.
Santanagálvez J, Cisneroszevallos L, Jacobovelázquez DA. Chlorogenic Acid: Recent Advances on Its Dual Role as a Food Additive and a Nutraceutical against Metabolic Syndrome. Molecules 2017; 22: 358.
Tajik N, Tajik M, Mack I, Enck P. The potential effects of chlorogenic acid, the main phenolic components in coffee, on health: a comprehensive review of the literature. Eur J Nutr. 2017: 1-30.
Deka SJ, Gorai S, Manna D, Trivedi V. Evidence of PKC Binding and Translocation to explain the anticancer mechanism of chlorogenic acid in breast cancer cells. Curr Mol Med 2017; 17: 79-89.
Gong L, Wu D, Zou J, Chen J, Chen L, Chen Y, et al. Prognostic impact of serum and tissue MMP-9 in non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget 2016; 7: 18458.
Wu A, Li J, Wu K, Mo Y, Luo Y, Ye H, et al. LATS2 as a poor prognostic marker regulates non-small cell lung cancer invasion by modulating MMPs expression. Biomed Pharmacother 2016; 82: 290-297.
Roach DM, Fitridge RA, Laws PE, Millard SH, Varelias A, Cowled PA. Up-regulation of MMP-2 and MMP-9 leads to degradation of type IV collagen during skeletal muscle reperfusion injury; protection by the MMP inhibitor, doxycycline. Eur J Vasc Endovasc Surg 2002; 23: 260-269.
Pacifico F, Leonardi A. NF-κB in solid tumors. Biochem Pharmacol 2006; 72: 1142-1152.
Li F, Zhang J, Arfuso F, Chinnathambi A, Zayed ME, Alharbi SA, et al. NF-κB in cancer therapy. Arch Toxicol 2015; 89: 1-21.