Synergistic anticancer effect of acteoside and temozolomide-based glioblastoma chemotherapy

Hwang,Tae   Woong; Kim,Dong   Hun; Kim,Da  Bi; Jang,Tae   Won; Kim,Gun‑Hwa; Moon,Minho; Yoon,Kyung   Ah; Choi,Dae   Eun; Park,Jae   Ho; Kim,Jwa‑Jin

doi:10.3892/ijmm.2019.4061

Synergistic anticancer effect of acteoside and temozolomide-based glioblastoma chemotherapy

Authors:
- Tae Woong Hwang
- Dong Hun Kim
- Da Bi Kim
- Tae Won Jang
- Gun‑Hwa Kim
- Minho Moon
- Kyung Ah Yoon
- Dae Eun Choi
- Jae Ho Park
- Jwa‑Jin Kim
View Affiliations

Affiliations: Department of Medical Science, School of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea, Department of Medicinal Plant Resources, Andong National University, Andong, Gyeongsangbuk 36729, Republic of Korea, Drug and Disease Target Team, Division of Bioconvergence Analysis, Korea Basic Science Institute, Cheongju, Chungcheong 28119, Republic of Korea, Department of Biochemistry, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea, Department of Clinical Laboratory Science, Daejeon Health Sciences College, Daejeon 34504, Republic of Korea, Department of Nephrology, School of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea, Department of Pharmaceutical Science, Jungwon University, Geosan, Chungbuk 28024, Republic of Korea
Published online on: January 11, 2019 https://doi.org/10.3892/ijmm.2019.4061
Pages: 1478-1486

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Temozolomide (TMZ) is an alkylating agent commonly used as a first‑line treatment for high‑grade glioblastoma. However, TMZ has short half‑life and frequently induces tumor resistance, which can limit its therapeutic efficiency. In the present study, it was hypothesized that combined treatment with TMZ and acteoside has synergistic effects in glioblastoma therapy. Using cell viability and wound‑healing assays, it was determined that this treatment regimen reduced cell viability and migration to a greater extent than either TMZ or acteoside alone. Following previous reports that TMZ affected autophagy in glioma cells, the present study examined the effects of TMZ + acteoside combination treatment on apoptosis and autophagy. The TMZ + acteoside combination treatment increased the cleavage of caspase‑3 and levels of B‑cell lymphoma 2 (Bcl‑2)‑associated X protein and phosphorylated p53, and decreased the level of Bcl‑2. The combination treatment increased microtubule‑associated protein 1 light chain 3 and apoptosis‑related gene expression. It was also determined that TMZ + acteoside induced apoptosis and autophagy through the mitogen‑activated protein kinase signaling pathway. These findings suggest that acteoside has beneficial effects on TMZ‑based glioblastoma therapy.

View Figures

View References

1	Friedman HS, Kerby T and Calvert H: Temozolomide and treatment of malignant glioma. Clin Cancer Res. 6:2585–2597. 2000.PubMed/NCBI
2	Mrugala MM and Chamberlain MC: Mechanisms of disease: Temozolomide and glioblastoma-look to the future. Nat Clin Pract Oncol. 5:476–486. 2008. View Article : Google Scholar : PubMed/NCBI
3	Agarwala SS and Kirkwood JM: Temozolomide, a novel alkylating agent with activity in the central nervous system, may improve the treatment of advanced metastatic melanoma. Oncologist. 5:144–151. 2000. View Article : Google Scholar : PubMed/NCBI
4	Stevens MF, Hickman JA, Stone R, Gibson NW, Baig GU, Lunt E and Newton CG: Antitumor imidazotetrazines. 1. Synthesis and chemistry of 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3, 5-tetrazin-4(3 H)-one, a novel broad-spectrum antitumor agent. J Med Chem. 27:196–201. 1984. View Article : Google Scholar : PubMed/NCBI
5	Fulda S: Cell death-based treatment of glioblastoma. Cell Death Dis. 9:1212018. View Article : Google Scholar : PubMed/NCBI
6	Chen PH, Shen WL, Shih CM, Ho KH, Cheng CH, Lin CW, Lee CC, Liu AJ and Chen KC: The CHAC1-inhibited Notch3 pathway is involved in temozolomide-induced glioma cytotoxicity. Neuropharmacology. 116:300–314. 2017. View Article : Google Scholar
7	Oshiro S, Tsugu H, Komatsu F, Ohmura T, Ohta M, Sakamoto S, Fukushima T and Inoue T: Efficacy of temozolomide treatment in patients with high-grade glioma. Anticancer Res. 29:911–917. 2009.PubMed/NCBI
8	van den Bent MJ: Adjuvant treatment of high grade gliomas. Ann Oncol. 17(Suppl 10): x186–x190. 2006. View Article : Google Scholar : PubMed/NCBI
9	Shen W, Hu JA and Zheng JS: Mechanism of temozolomide-induced antitumour effects on glioma cells. J Int Med Res. 42:164–172. 2014. View Article : Google Scholar
10	Barciszewska AM, Gurda D, Głodowicz P, Nowak S and Naskręt-Barciszewska MZ: A new epigenetic mechanism of temozolomide action in glioma cells. PLoS One. 10:e01366692015. View Article : Google Scholar : PubMed/NCBI
11	Cai X and Sughrue ME: Glioblastoma: New therapeutic strategies to address cellular and genomic complexity. Oncotarget. 9:9540–9554. 2018. View Article : Google Scholar : PubMed/NCBI
12	Zhang J, Stevens MF and Bradshaw TD: Temozolomide: Mechanisms of action, repair and resistance. Curr Mol Pharmacol. 5:102–114. 2012. View Article : Google Scholar
13	Johannessen TC and Bjerkvig R: Molecular mechanisms of temozolomide resistance in glioblastoma multiforme. Expert Rev Anticancer Ther. 12:635–642. 2012. View Article : Google Scholar : PubMed/NCBI
14	Yan Y, Xu Z, Dai S, Qian L, Sun L and Gong Z: Targeting autophagy to sensitive glioma to temozolomide treatment. J Exp Clin Cancer Res. 35:232016. View Article : Google Scholar : PubMed/NCBI
15	Bak DH, Kang SH, Choi DR, Gil MN, Yu KS, Jeong JH, Lee NS, Lee JH, Jeong YG, Kim DK, et al: Autophagy enhancement contributes to the synergistic effect of vitamin D in temozolomide-based glioblastoma chemotherapy. Exp Ther Med. 11:2153–2162. 2016. View Article : Google Scholar : PubMed/NCBI
16	Li C, Liu Y, Liu H, Zhang W, Shen C, Cho K, Chen X, Peng F, Bi Y, Hou X, et al: Impact of autophagy inhibition at different stages on cytotoxic effect of autophagy inducer in glioblastoma cells. Cell Physiol Biochem. 35:1303–1316. 2015. View Article : Google Scholar : PubMed/NCBI
17	Ni H, Gong Y, Yan JZ and Zhang LL: Autophagy inhibitor 3-methyladenine regulates the expression of LC3, Beclin-1 and ZnTs in rat cerebral cortex following recurrent neonatal seizures. World J Emerg Med. 1:216–223. 2010.PubMed/NCBI
18	Xie Z and Klionsky DJ: Autophagosome formation: Core machinery and adaptations. Nat Cell Biol. 9:1102–1109. 2007. View Article : Google Scholar : PubMed/NCBI
19	Gutierrez MG, Master SS, Singh SB, Taylor GA, Colombo MI and Deretic V: Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell. 119:753–766. 2004. View Article : Google Scholar : PubMed/NCBI
20	Wu YT, Wu MT, Lin CC, Chien CF and Tsai TH: Pharmacokinetic studies of chinese medicinal herbs using an automated blood sampling system and liquid chromatography-mass spectrometry. J Tradit Complement Med. 2:33–40. 2012. View Article : Google Scholar : PubMed/NCBI
21	Inoue M, Sakuma Z, Ogihara Y and Saracoglu I: Induction of apoptotic cell death in HL-60 cells by acteoside, a phenylpropanoid glycoside. Biol Pharm Bull. 21:81–83. 1998. View Article : Google Scholar : PubMed/NCBI
22	Ohno T, Inoue M, Ogihara Y and Saracoglu I: Antimetastatic activity of acteoside, a phenylethanoid glycoside. Biol Pharm Bull. 25:666–668. 2002. View Article : Google Scholar : PubMed/NCBI
23	Lee KJ, Woo ER, Choi CY, Shin DW, Lee DG, You HJ and Jeong HG: Protective effect of acteoside on carbon tetrachloride-induced hepatotoxicity. Life Sci. 74:1051–1064. 2004. View Article : Google Scholar
24	Peerzada KJ, Faridi AH, Sharma L, Bhardwaj SC, Satti NK, Shashi B and Tasduq SA: Acteoside-mediates chemoprevention of experimental liver carcinogenesis through STAT-3 regulated oxidative stress and apoptosis. Environ Toxicol. 31:782–798. 2016. View Article : Google Scholar : PubMed/NCBI
25	Zhao J, Liu T, Ma L, Yan M, Zhao Y, Gu Z and Huang Y: Protective effect of acteoside on immunological liver injury induced by Bacillus Calmette-Guerin plus lipopolysaccharide. Planta Med. 75:1463–1469. 2009. View Article : Google Scholar : PubMed/NCBI
26	Xiong Q, Hase K, Tezuka Y, Tani T, Namba T and Kadota S: Hepatoprotective activity of phenylethanoids from Cistanche deserticola. Planta Med. 64:120–125. 1998. View Article : Google Scholar : PubMed/NCBI
27	Koh DS, Seo BS and Lee CH: Studies on the in vitro induction of callus from anther culture of Abeliophyllum distichum. J Chonbuk Natl Univ. 31:153–159. 1989.In Korean.
28	Würstle S, Schneider F, Ringel F, Gempt J, Lämmer F, Delbridge C, Wu W and Schlegel J: Temozolomide induces autophagy in primary and established glioblastoma cells in an EGFR independent manner. Oncol Lett. 14:322–328. 2017. View Article : Google Scholar : PubMed/NCBI
29	Koukourakis MI, Mitrakas AG and Giatromanolaki A: Therapeutic interactions of autophagy with radiation and temozolomide in glioblastoma: Evidence and issues to resolve. Br J Cancer. 114:485–496. 2016. View Article : Google Scholar : PubMed/NCBI
30	Chen Y, Gao F, Jiang R, Liu H, Hou J, Yi Y, Kang L, Liu X, Li Y and Yang M: Down-regulation of AQP4 expression via p38 MAPK signaling in temozolomide-induced glioma cells growth inhibition and invasion impairment. J Cell Biochem. 118:4905–4913. 2017. View Article : Google Scholar : PubMed/NCBI
31	He C and Klionsky DJ: Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet. 43:67–93. 2009. View Article : Google Scholar : PubMed/NCBI
32	Bento CF, Renna M, Ghislat G, Puri C, Ashkenazi A, Vicinanza M, Menzies FM and Rubinsztein DC: Mammalian autophagy: How does it work? Annu Rev Biochem. 85:685–713. 2016. View Article : Google Scholar : PubMed/NCBI
33	Levine B, Mizushima N and Virgin HW: Autophagy in immunity and inflammation. Nature. 469:323–335. 2011. View Article : Google Scholar : PubMed/NCBI
34	Fulda S: Autophagy in Cancer Therapy. Front Oncol. 7:1282017. View Article : Google Scholar : PubMed/NCBI
35	Levy JMM, Towers CG and Thorburn A: Targeting autophagy in cancer. Nat Rev Cancer. 17:528–542. 2017. View Article : Google Scholar : PubMed/NCBI
36	White E: The role for autophagy in cancer. J Clin Invest. 125:42–46. 2015. View Article : Google Scholar : PubMed/NCBI
37	Aoki H, Kondo Y, Aldape K, Yamamoto A, Iwado E, Yokoyama T, Hollingsworth EF, Kobayashi R, Hess K, Shinojima N, et al: Monitoring autophagy in glioblastoma with antibody against isoform B of human microtubule-associated protein 1 light chain 3. Autophagy. 4:467–475. 2008. View Article : Google Scholar : PubMed/NCBI
38	Cj P, Hv E, Vijayakurup V, R Menon G, Nair S and Gopala S: High LC3/beclin expression correlates with poor survival in glioma: A definitive role for autophagy as evidenced by in vitro autophagic flux. Pathol Oncol Res. Oct 11–2017.PubMed/NCBI
39	Monastyrska I and Klionsky DJ: Autophagy in organelle homeostasis: Peroxisome turnover. Mol Aspects Med. 27:483–494. 2006. View Article : Google Scholar : PubMed/NCBI
40	Farre JC and Subramani S: Peroxisome turnover by micropexophagy: An autophagy-related process. Trends Cell Biol. 14:515–523. 2004. View Article : Google Scholar : PubMed/NCBI
41	Singh R and Cuervo AM: Autophagy in the cellular energetic balance. Cell Metab. 13:495–504. 2011. View Article : Google Scholar : PubMed/NCBI