Skip to main content
Top
Published in: BMC Complementary Medicine and Therapies 1/2019

Open Access 01-12-2019 | Colon Cancer | Research article

Ethanol extract of Chrysanthemum zawadskii Herbich induces autophagy and apoptosis in mouse colon cancer cells through the regulation of reactive oxygen species

Authors: Kwang-Youn Kim, Tae-Woo Oh, Hye-Jin Yang, Young-Woo Kim, Jin-Yeul Ma, Kwang-Il Park

Published in: BMC Complementary Medicine and Therapies | Issue 1/2019

Login to get access

Abstract

Background

Recent research has suggested that autophagy can provide a better mechanism for inducing cell death than current therapeutic strategies. This study investigated the effects of using an ethanol extract of Chrysanthemum zawadskii Herbich (ECZ) to induce apoptosis and autophagy associated with reliable signal pathways in mouse colon cancer CT-26 cells.

Methods

Using ECZ on mouse colon cancer CT-26 cells, cell viability, annexin V/propidium iodide staining, acridine orange staining, reactive oxygen species (ROS) and western blotting were assayed.

Results

ECZ exhibited cytotoxicity in CT-26 cells in a dose-dependent manner. ECZ induced apoptosis was confirmed by caspase-3 activation, poly (ADP-ribose) polymerase cleavage, and increased production of reactive oxygen species (ROS). Furthermore, it was shown that ECZ induced autophagy via the increased conversion of microtubule-associated protein 1 light chain 3II, the degradation of p62, and the formation of acidic vesicular organelles. The inhibition of ROS production by N-Acetyl-L-cysteine resulted in reduced ECZ-induced apoptosis and autophagy. Furthermore, the inhibition of autophagy by 3-methyladenine resulted in enhanced ECZ-induced apoptosis via increased ROS generation.

Conclusion

These findings confirmed that ECZ induced ROS-mediated autophagy and apoptosis in colon cancer cells. Therefore, ECZ may serve as a novel potential chemotherapeutic candidate for colon cancer.
Appendix
Available only for authorised users
Literature
1.
go back to reference Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomark Prev. 2010;19(8):1893–907.CrossRef Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomark Prev. 2010;19(8):1893–907.CrossRef
6.
go back to reference Liu Y, Levine B. Autosis and autophagic cell death: the dark side of autophagy. Cell Death Differ. 2015;22(3):367–76.PubMedCrossRef Liu Y, Levine B. Autosis and autophagic cell death: the dark side of autophagy. Cell Death Differ. 2015;22(3):367–76.PubMedCrossRef
7.
8.
go back to reference El-Khattouti A, Selimovic D, Haikel Y, Hassan M. Crosstalk between apoptosis and autophagy: molecular mechanisms and therapeutic strategies in cancer. J Cell Death. 2013;6:37–55.PubMedPubMedCentralCrossRef El-Khattouti A, Selimovic D, Haikel Y, Hassan M. Crosstalk between apoptosis and autophagy: molecular mechanisms and therapeutic strategies in cancer. J Cell Death. 2013;6:37–55.PubMedPubMedCentralCrossRef
9.
go back to reference Zhou Y, Rucker EB 3rd, Zhou BP. Autophagy regulation in the development and treatment of breast cancer. Acta Biochim Biophys Sin (Shanghai). 2016;48(1):60–74. Zhou Y, Rucker EB 3rd, Zhou BP. Autophagy regulation in the development and treatment of breast cancer. Acta Biochim Biophys Sin (Shanghai). 2016;48(1):60–74.
12.
go back to reference Kim SH, Choi YJ, Kim KY, Yu SN, Seo YK, Chun SS, Noh KT, Suh JT, Ahn SC. Salinomycin simultaneously induces apoptosis and autophagy through generation of reactive oxygen species in osteosarcoma U2OS cells. Biochem Biophys Res Commun. 2016;473(2):607–13.PubMedCrossRef Kim SH, Choi YJ, Kim KY, Yu SN, Seo YK, Chun SS, Noh KT, Suh JT, Ahn SC. Salinomycin simultaneously induces apoptosis and autophagy through generation of reactive oxygen species in osteosarcoma U2OS cells. Biochem Biophys Res Commun. 2016;473(2):607–13.PubMedCrossRef
13.
go back to reference Kim KY, Kim SH, Yu SN, Park SG, Kim YW, Nam HW, An HH, Yu HS, Kim YW, Ji JH, et al. Lasalocid induces cytotoxic apoptosis and cytoprotective autophagy through reactive oxygen species in human prostate cancer PC-3 cells. Biomed Pharmacother. 2017;88:1016–24.PubMedCrossRef Kim KY, Kim SH, Yu SN, Park SG, Kim YW, Nam HW, An HH, Yu HS, Kim YW, Ji JH, et al. Lasalocid induces cytotoxic apoptosis and cytoprotective autophagy through reactive oxygen species in human prostate cancer PC-3 cells. Biomed Pharmacother. 2017;88:1016–24.PubMedCrossRef
14.
go back to reference Kim KY, Park KI, Kim SH, Yu SN, Park SG, Kim YW, Seo YK, Ma JY, Ahn SC. Inhibition of Autophagy Promotes Salinomycin-Induced Apoptosis via Reactive Oxygen Species-Mediated PI3K/AKT/mTOR and ERK/p38 MAPK-Dependent Signaling in Human Prostate Cancer Cells. Int J Mol Sci. 2017;18(5).PubMedCentralCrossRef Kim KY, Park KI, Kim SH, Yu SN, Park SG, Kim YW, Seo YK, Ma JY, Ahn SC. Inhibition of Autophagy Promotes Salinomycin-Induced Apoptosis via Reactive Oxygen Species-Mediated PI3K/AKT/mTOR and ERK/p38 MAPK-Dependent Signaling in Human Prostate Cancer Cells. Int J Mol Sci. 2017;18(5).PubMedCentralCrossRef
15.
go back to reference Zhan Y, Gong K, Chen C, Wang H, Li W. P38 MAP kinase functions as a switch in MS-275-induced reactive oxygen species-dependent autophagy and apoptosis in human colon cancer cells. Free Radic Biol Med. 2012;53(3):532–43.PubMedCrossRef Zhan Y, Gong K, Chen C, Wang H, Li W. P38 MAP kinase functions as a switch in MS-275-induced reactive oxygen species-dependent autophagy and apoptosis in human colon cancer cells. Free Radic Biol Med. 2012;53(3):532–43.PubMedCrossRef
16.
go back to reference Seo JY, Lim SS, Park J, Lim JS, Kim HJ, Kang HJ, Yoon Park JH, Kim JS. Protection by Chrysanthemum zawadskii extract from liver damage of mice caused by carbon tetrachloride is maybe mediated by modulation of QR activity. Nutr Res Pract. 2010;4(2):93–8.PubMedPubMedCentralCrossRef Seo JY, Lim SS, Park J, Lim JS, Kim HJ, Kang HJ, Yoon Park JH, Kim JS. Protection by Chrysanthemum zawadskii extract from liver damage of mice caused by carbon tetrachloride is maybe mediated by modulation of QR activity. Nutr Res Pract. 2010;4(2):93–8.PubMedPubMedCentralCrossRef
17.
go back to reference Sassi AB, Harzallah-Skhiri F, Bourgougnon N, Aouni M. Antimicrobial activities of four Tunisian Chrysanthemum species. Indian J Med Res. 2008;127(2):183–92.PubMed Sassi AB, Harzallah-Skhiri F, Bourgougnon N, Aouni M. Antimicrobial activities of four Tunisian Chrysanthemum species. Indian J Med Res. 2008;127(2):183–92.PubMed
18.
go back to reference Liu Q, Liu H, Yuan Z, Wei D, Ye Y. Evaluation of antioxidant activity of chrysanthemum extracts and tea beverages by gold nanoparticles-based assay. Colloids Surf B Biointerfaces. 2012;92:348–52.PubMedCrossRef Liu Q, Liu H, Yuan Z, Wei D, Ye Y. Evaluation of antioxidant activity of chrysanthemum extracts and tea beverages by gold nanoparticles-based assay. Colloids Surf B Biointerfaces. 2012;92:348–52.PubMedCrossRef
19.
go back to reference He J, Chen F, Chen S, Lv G, Deng Y, Fang W, Liu Z, Guan Z, He C. Chrysanthemum leaf epidermal surface morphology and antioxidant and defense enzyme activity in response to aphid infestation. J Plant Physiol. 2011;168(7):687–93.PubMedCrossRef He J, Chen F, Chen S, Lv G, Deng Y, Fang W, Liu Z, Guan Z, He C. Chrysanthemum leaf epidermal surface morphology and antioxidant and defense enzyme activity in response to aphid infestation. J Plant Physiol. 2011;168(7):687–93.PubMedCrossRef
20.
go back to reference Kim SJ, Cho HI, Kim SJ, Park JH, Kim JS, Kim YH, Lee SK, Kwak JH, Lee SM. Protective effect of linarin against D-galactosamine and lipopolysaccharide-induced fulminant hepatic failure. Eur J Pharmacol. 2014;738:66–73.PubMedCrossRef Kim SJ, Cho HI, Kim SJ, Park JH, Kim JS, Kim YH, Lee SK, Kwak JH, Lee SM. Protective effect of linarin against D-galactosamine and lipopolysaccharide-induced fulminant hepatic failure. Eur J Pharmacol. 2014;738:66–73.PubMedCrossRef
21.
go back to reference Zhen ZG, Ren SH, Ji HM, Ma JH, Ding XM, Feng FQ, Chen SL, Zou P, Ren JR, Jia L. Linarin suppresses glioma through inhibition of NF-kappaB/p65 and up-regulating p53 expression in vitro and in vivo. Biomed Pharmacother. 2017;95:363–74.PubMedCrossRef Zhen ZG, Ren SH, Ji HM, Ma JH, Ding XM, Feng FQ, Chen SL, Zou P, Ren JR, Jia L. Linarin suppresses glioma through inhibition of NF-kappaB/p65 and up-regulating p53 expression in vitro and in vivo. Biomed Pharmacother. 2017;95:363–74.PubMedCrossRef
22.
go back to reference Chen X, Zhang S, Xuan Z, Ge D, Chen X, Zhang J, Wang Q, Wu Y, Liu B. The Phenolic Fraction of Mentha haplocalyx and Its Constituent Linarin Ameliorate Inflammatory Response through Inactivation of NF-kappaB and MAPKs in Lipopolysaccharide-Induced RAW264.7 Cells. Molecules. 2017;22(5).PubMedCentralCrossRef Chen X, Zhang S, Xuan Z, Ge D, Chen X, Zhang J, Wang Q, Wu Y, Liu B. The Phenolic Fraction of Mentha haplocalyx and Its Constituent Linarin Ameliorate Inflammatory Response through Inactivation of NF-kappaB and MAPKs in Lipopolysaccharide-Induced RAW264.7 Cells. Molecules. 2017;22(5).PubMedCentralCrossRef
23.
go back to reference Yang PF, Feng ZM, Yang YN, Jiang JS, Zhang PC. Neuroprotective Caffeoylquinic acid derivatives from the flowers of Chrysanthemum morifolium. J Nat Prod. 2017;80(4):1028–33.PubMedCrossRef Yang PF, Feng ZM, Yang YN, Jiang JS, Zhang PC. Neuroprotective Caffeoylquinic acid derivatives from the flowers of Chrysanthemum morifolium. J Nat Prod. 2017;80(4):1028–33.PubMedCrossRef
24.
go back to reference Qin S, Wen X. simultaneous determination of 6 active components in Chrysanthemum morifolium by HPLC. Zhongguo Zhong Yao Za Zhi. 2011;36(11):1474–7.PubMed Qin S, Wen X. simultaneous determination of 6 active components in Chrysanthemum morifolium by HPLC. Zhongguo Zhong Yao Za Zhi. 2011;36(11):1474–7.PubMed
26.
go back to reference Zhang T, Li Y, Park KA, Byun HS, Won M, Jeon J, Lee Y, Seok JH, Choi SW, Lee SH, et al. Cucurbitacin induces autophagy through mitochondrial ROS production which counteracts to limit caspase-dependent apoptosis. Autophagy. 2012;8(4):559–76.PubMedCrossRef Zhang T, Li Y, Park KA, Byun HS, Won M, Jeon J, Lee Y, Seok JH, Choi SW, Lee SH, et al. Cucurbitacin induces autophagy through mitochondrial ROS production which counteracts to limit caspase-dependent apoptosis. Autophagy. 2012;8(4):559–76.PubMedCrossRef
27.
go back to reference Park MJ, Song JH, Shon MS, Kim HO, Kwon OJ, Roh SS, Kim CY, Kim GN. Anti-Adipogenic effects of ethanol extracts prepared from selected medicinal herbs in 3T3-L1 cells. Prev Nutr Food Sci. 2016;21(3):227–35.PubMedPubMedCentralCrossRef Park MJ, Song JH, Shon MS, Kim HO, Kwon OJ, Roh SS, Kim CY, Kim GN. Anti-Adipogenic effects of ethanol extracts prepared from selected medicinal herbs in 3T3-L1 cells. Prev Nutr Food Sci. 2016;21(3):227–35.PubMedPubMedCentralCrossRef
28.
go back to reference Han S, Sung KH, Yim D, Lee S, Lee CK, Ha NJ, Kim K. The effect of linarin on LPS-induced cytokine production and nitric oxide inhibition in murine macrophages cell line RAW264.7. Arch Pharm Res. 2002;25(2):170–7.PubMedCrossRef Han S, Sung KH, Yim D, Lee S, Lee CK, Ha NJ, Kim K. The effect of linarin on LPS-induced cytokine production and nitric oxide inhibition in murine macrophages cell line RAW264.7. Arch Pharm Res. 2002;25(2):170–7.PubMedCrossRef
29.
go back to reference Wu TY, Khor TO, Saw CL, Loh SC, Chen AI, Lim SS, Park JH, Cai L, Kong AN. Anti-inflammatory/anti-oxidative stress activities and differential regulation of Nrf2-mediated genes by non-polar fractions of tea Chrysanthemum zawadskii and licorice Glycyrrhiza uralensis. AAPS J. 2011;13(1):1–13.PubMedCrossRef Wu TY, Khor TO, Saw CL, Loh SC, Chen AI, Lim SS, Park JH, Cai L, Kong AN. Anti-inflammatory/anti-oxidative stress activities and differential regulation of Nrf2-mediated genes by non-polar fractions of tea Chrysanthemum zawadskii and licorice Glycyrrhiza uralensis. AAPS J. 2011;13(1):1–13.PubMedCrossRef
30.
31.
go back to reference Kim SH, Kim KY, Yu SN, Park SK, Choi HD, Ji JH, Ahn SC. Autophagy inhibition enhances silibinin-induced apoptosis by regulating reactive oxygen species production in human prostate cancer PC-3 cells. Biochem Biophys Res Commun. 2015;468(1–2):151–6.PubMedCrossRef Kim SH, Kim KY, Yu SN, Park SK, Choi HD, Ji JH, Ahn SC. Autophagy inhibition enhances silibinin-induced apoptosis by regulating reactive oxygen species production in human prostate cancer PC-3 cells. Biochem Biophys Res Commun. 2015;468(1–2):151–6.PubMedCrossRef
32.
go back to reference Ouyang L, Shi Z, Zhao S, Wang FT, Zhou TT, Liu B, Bao JK. Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis. Cell Prolif. 2012;45(6):487–98.PubMedCrossRefPubMedCentral Ouyang L, Shi Z, Zhao S, Wang FT, Zhou TT, Liu B, Bao JK. Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis. Cell Prolif. 2012;45(6):487–98.PubMedCrossRefPubMedCentral
33.
go back to reference Pan X, Zhang X, Sun H, Zhang J, Yan M, Zhang H. Autophagy inhibition promotes 5-fluorouraci-induced apoptosis by stimulating ROS formation in human non-small cell lung cancer A549 cells. PLoS One. 2013;8(2):e56679.PubMedPubMedCentralCrossRef Pan X, Zhang X, Sun H, Zhang J, Yan M, Zhang H. Autophagy inhibition promotes 5-fluorouraci-induced apoptosis by stimulating ROS formation in human non-small cell lung cancer A549 cells. PLoS One. 2013;8(2):e56679.PubMedPubMedCentralCrossRef
34.
go back to reference Yuan L, Wei S, Wang J, Liu X. Isoorientin induces apoptosis and autophagy simultaneously by reactive oxygen species (ROS)-related p53, PI3K/Akt, JNK, and p38 signaling pathways in HepG2 cancer cells. J Agric Food Chem. 2014;62(23):5390–400.PubMedCrossRef Yuan L, Wei S, Wang J, Liu X. Isoorientin induces apoptosis and autophagy simultaneously by reactive oxygen species (ROS)-related p53, PI3K/Akt, JNK, and p38 signaling pathways in HepG2 cancer cells. J Agric Food Chem. 2014;62(23):5390–400.PubMedCrossRef
35.
go back to reference Miki H, Uehara N, Kimura A, Sasaki T, Yuri T, Yoshizawa K, Tsubura A. Resveratrol induces apoptosis via ROS-triggered autophagy in human colon cancer cells. Int J Oncol. 2012;40(4):1020–8.PubMedPubMedCentralCrossRef Miki H, Uehara N, Kimura A, Sasaki T, Yuri T, Yoshizawa K, Tsubura A. Resveratrol induces apoptosis via ROS-triggered autophagy in human colon cancer cells. Int J Oncol. 2012;40(4):1020–8.PubMedPubMedCentralCrossRef
36.
go back to reference Hao W, Zhang X, Zhao W, Chen X. Psoralidin induces autophagy through ROS generation which inhibits the proliferation of human lung cancer A549 cells. PeerJ. 2014;2:e555.PubMedPubMedCentralCrossRef Hao W, Zhang X, Zhao W, Chen X. Psoralidin induces autophagy through ROS generation which inhibits the proliferation of human lung cancer A549 cells. PeerJ. 2014;2:e555.PubMedPubMedCentralCrossRef
Metadata
Title
Ethanol extract of Chrysanthemum zawadskii Herbich induces autophagy and apoptosis in mouse colon cancer cells through the regulation of reactive oxygen species
Authors
Kwang-Youn Kim
Tae-Woo Oh
Hye-Jin Yang
Young-Woo Kim
Jin-Yeul Ma
Kwang-Il Park
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2019
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-019-2688-0

Other articles of this Issue 1/2019

BMC Complementary Medicine and Therapies 1/2019 Go to the issue