Athyrium Multidentatum (Doll.) Ching Extract Induce Apoptosis Via Mitochondrial Dysfunction and Oxidative Stress in HepG2 Cells

Overview

Journal Sci Rep

Specialty Science

Date 2017 May 25

PMID 28536473

Citations 7

Authors

Guoyuan Qi

Zhigang Liu

Rong Fan

Ziru Yin

Yashi Mi

Bo Ren

Xuebo Liu

Affiliations

Soon will be listed here.

Abstract

Athyrium multidentatum (Doll.) Ching (AMC), a unique and nutritious potherb widely distributed in china, has been extensively used in traditional Chinese medicine. Previous studies indicated that AMC extract exhibited antioxidant and antitumor properties. However, the chemical composition of AMC and molecular mechanism of AMC toxicity to HepG2 cells have not yet been elucidated. Hence, this study aimed to investigate the chemical compositions and the underlying mechanisms of the antiproliferative and apoptotic effects of AMC on HepG2. HPLC-MS analysis showed that AMC contain five compounds with chlorogenic acid accounting for 43 percent. Also, AMC strongly inhibited the cell growth and induced apoptosis and cell cycle arrest in HepG2 cells by significantly upregulating the protein expressions of Fas, Fas-L, Bax/Bcl-2, cyto-c, cleaved caspase-3, and PARP in a dose-dependent manner, which indicates AMC induces apoptosis in HepG2 cells through both intrinsic and extrinsic pathways. Moreover, AMC provoked the production of ROS, HO, and NO, modulating the PI3K/Akt, MAPK, NFκB and Nrf2 pathways and their downstream transcriptional cascades, ultimately evoked oxidative stress and apoptosis in HpeG2 cells. Further in vivo experiments demonstrated that AMC significantly suppressed the tumor growth, suggesting that AMC may be a novel promising agent for hepatocellular carcinoma treatment.

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References

Kuo C, Hsu M, Chen B, Chen C, Teng C, Pan S . Denbinobin induces apoptosis in human lung adenocarcinoma cells via Akt inactivation, Bad activation, and mitochondrial dysfunction. Toxicol Lett. 2008; 177(1):48-58. DOI: 10.1016/j.toxlet.2007.12.009. View

Peng X, Zhang Y, Wang J, Ji Q . Ethylacetate extract from Tetrastigma hemsleyanum induces apoptosis via the mitochondrial caspase-dependent intrinsic pathway in HepG2 cells. Tumour Biol. 2015; 37(1):865-76. DOI: 10.1007/s13277-015-3579-8. View

Lee K . Discovery and development of natural product-derived chemotherapeutic agents based on a medicinal chemistry approach. J Nat Prod. 2010; 73(3):500-16. PMC: 2893734. DOI: 10.1021/np900821e. View

Srivastava M, Nambiar M, Sharma S, Karki S, Goldsmith G, Hegde M . An inhibitor of nonhomologous end-joining abrogates double-strand break repair and impedes cancer progression. Cell. 2012; 151(7):1474-87. DOI: 10.1016/j.cell.2012.11.054. View

Deng S, Tang S, Zhang S, Zhang C, Wang C, Zhou Y . Furazolidone induces apoptosis through activating reactive oxygen species-dependent mitochondrial signaling pathway and suppressing PI3K/Akt signaling pathway in HepG2 cells. Food Chem Toxicol. 2014; 75:173-86. DOI: 10.1016/j.fct.2014.11.019. View

Taguchi K, Motohashi H, Yamamoto M . Molecular mechanisms of the Keap1–Nrf2 pathway in stress response and cancer evolution. Genes Cells. 2011; 16(2):123-40. DOI: 10.1111/j.1365-2443.2010.01473.x. View

Wang H, Ye Y, Chui J, Zhu G, Li Y, Fong D . Oridonin induces G2/M cell cycle arrest and apoptosis through MAPK and p53 signaling pathways in HepG2 cells. Oncol Rep. 2010; 24(3):647-51. View

Zingarelli B, Sheehan M, Wong H . Nuclear factor-kappaB as a therapeutic target in critical care medicine. Crit Care Med. 2003; 31(1 Suppl):S105-11. DOI: 10.1097/00003246-200301001-00015. View

Liu D, Sheng J, Li Z, Qi H, Sun Y, Duan Y . Antioxidant activity of polysaccharide fractions extracted from Athyrium multidentatum (Doll.) Ching. Int J Biol Macromol. 2013; 56:1-5. DOI: 10.1016/j.ijbiomac.2013.01.023. View

10.

Gao H, Wang H, Peng J . Hispidulin induces apoptosis through mitochondrial dysfunction and inhibition of P13k/Akt signalling pathway in HepG2 cancer cells. Cell Biochem Biophys. 2013; 69(1):27-34. DOI: 10.1007/s12013-013-9762-x. View

11.

Chao X, Zao J, Xiao-Yi G, Li-Jun M, Tao S . Blocking of PI3K/AKT induces apoptosis by its effect on NF-κB activity in gastric carcinoma cell line SGC7901. Biomed Pharmacother. 2010; 64(9):600-4. DOI: 10.1016/j.biopha.2010.08.008. View

12.

Li Y, Duan S, Jia H, Bai C, Zhang L, Wang Z . Flavonoids from tartary buckwheat induce G2/M cell cycle arrest and apoptosis in human hepatoma HepG2 cells. Acta Biochim Biophys Sin (Shanghai). 2014; 46(6):460-70. DOI: 10.1093/abbs/gmu023. View

13.

Cheng Y, Qiu F, Ye Y, Tashiro S, Onodera S, Ikejima T . Oridonin induces G2/M arrest and apoptosis via activating ERK-p53 apoptotic pathway and inhibiting PTK-Ras-Raf-JNK survival pathway in murine fibrosarcoma L929 cells. Arch Biochem Biophys. 2009; 490(1):70-5. DOI: 10.1016/j.abb.2009.08.011. View

14.

Sharma L, Lu J, Bai Y . Mitochondrial respiratory complex I: structure, function and implication in human diseases. Curr Med Chem. 2009; 16(10):1266-77. PMC: 4706149. DOI: 10.2174/092986709787846578. View

15.

Qurishi Y, Hamid A, Majeed R, Hussain A, Qazi A, Ahmed M . Interaction of natural products with cell survival and signaling pathways in the biochemical elucidation of drug targets in cancer. Future Oncol. 2011; 7(8):1007-21. DOI: 10.2217/fon.11.69. View

16.

Cui H, Wu S, Sun Y, Wang T, Li Z, Chen M . Polysaccharide from Pleurotus nebrodensis induces apoptosis via a mitochondrial pathway in HepG2 cells. Food Funct. 2015; 7(1):455-63. DOI: 10.1039/c5fo00884k. View

17.

Liu W, Huang X, Qi Q, Dai Q, Yang L, Nie F . Asparanin A induces G(2)/M cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells. Biochem Biophys Res Commun. 2009; 381(4):700-5. DOI: 10.1016/j.bbrc.2009.02.124. View

18.

Kroemer G, Reed J . Mitochondrial control of cell death. Nat Med. 2000; 6(5):513-9. DOI: 10.1038/74994. View

19.

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. DOI: 10.1021/jf500903g. View

20.

Fato R, Bergamini C, Leoni S, Strocchi P, Lenaz G . Generation of reactive oxygen species by mitochondrial complex I: implications in neurodegeneration. Neurochem Res. 2008; 33(12):2487-501. DOI: 10.1007/s11064-008-9747-0. View