Ampelopsin‑sodium induces apoptosis in human lung adenocarcinoma cell lines by promoting tubulin polymerization in vitro

Zhu,Lijuan; Zhang,Baolai; Luo,Jianyun; Dong,Shuhong; Zang,Kaihong; Wu,Yongjie

doi:10.3892/ol.2019.10288

Ampelopsin‑sodium induces apoptosis in human lung adenocarcinoma cell lines by promoting tubulin polymerization in vitro

Authors:
- Lijuan Zhu
- Baolai Zhang
- Jianyun Luo
- Shuhong Dong
- Kaihong Zang
- Yongjie Wu
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Affiliations: Department of Pharmacology, School of Basic Medical Science, Lanzhou University, Lanzhou, Gansu 730000, P.R. China, Department of Drug Policy and Essential Medicine, Xi'an Municipal Health Commission, Xi'an, Shaanxi 710000, P.R. China, Department of Pharmacology, College of Pharmacy, Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu 730000, P.R. China
Published online on: April 30, 2019 https://doi.org/10.3892/ol.2019.10288
Pages: 189-196
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Previous studies have demonstrated that ampelopsin (AMP), a type of flavonoid isolated from the stems and leaves of Ampelopsis grossedentata, exhibits anti‑cancer activity in various types of cancer. Conversion of AMP into its sodium salt (AMP‑Na) conferred enhanced solubility and stability to it. The present study aimed to evaluate the anti‑cancer activity of AMP‑Na in human lung adenocarcinoma cell lines and to investigate its mechanisms of action. Cell proliferation and viability were assessed by MTT and colony formation assays, and cell migration was determined using a scratch wound healing assay. The cell cycle distribution, apoptosis rate and tubulin immunofluorescence intensity were analyzed using flow cytometry, the cell ultra‑microstructure was examined using transmission electron microscopy and the accumulation of tubulin was determined using laser confocal microscopy. The results demonstrated that AMP‑Na significantly inhibited the proliferation, clonogenicity and migration of human lung adenocarcinoma cells. Furthermore, AMP‑Na induced SPC‑A‑1 cell apoptosis, and promoted tubulin polymerization. The results suggested that the underlying mechanisms of AMP‑Na may involve targeting of microtubules and tubulin polymerization to subsequently disrupt mitosis and induce cell cycle arrest at the S‑phase.

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1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Hua F, Shang S and Hu ZW: Seeking new anti-cancer agents from autophagy-regulating natural products. J Asian Nat Prod Res. 19:305–313. 2017. View Article : Google Scholar : PubMed/NCBI
3	Nazir HF, AlFutaisi A, Zacharia M, Elshinawy M, Mevada ST, Alrawas A, Khater D, Jaju D and Wali Y: Vincristine-induced neuropathy in pediatric patients with acute lymphoblastic leukemia in Oman: Frequent autonomic and more severe cranial nerve involvement. Pediatr Blood Cancer. 64:2017. View Article : Google Scholar : PubMed/NCBI
4	Khongkow M, Olmos Y, Gong C, Gomes AR, Monteiro LJ, Yague E, Cavaco TB, Khongkow P, Man EP, Laohasinnarong S, et al: SIRT6 modulates paclitaxel and epirubicin resistance and survival in breast cancer. Carcinogenesis. 34:1476–1486. 2013. View Article : Google Scholar : PubMed/NCBI
5	Chen XM, Xie XB, Zhao Q, Wang F, Bai Y, Yin JQ, Jiang H, Xie XL, Jia Q and Huang G: Ampelopsin induces apoptosis by regulating multiple c-Myc/S-phase kinase-associated protein 2/F-box and WD repeat-containing protein 7/histone deacetylase 2 pathways in human lung adenocarcinoma cells. Mol Med Rep. 11:105–112. 2015. View Article : Google Scholar : PubMed/NCBI
6	Zhou Y, Shu F, Liang X, Chang H, Shi L, Peng X, Zhu J and Mi M: Ampelopsin induces cell growth inhibition and apoptosis in breast cancer cells through ROS generation and endoplasmic reticulum stress pathway. PLoS One. 9:e890212014. View Article : Google Scholar : PubMed/NCBI
7	Zheng HQ and Liu DY: Anti-invasive and anti-metastatic effect of ampelopsin on melanoma. Ai Zheng. 22:363–367. 2003.(In Chinese). PubMed/NCBI
8	Qi S, Kou X, Lv J, Qi Z and Yan L: Ampelopsin induces apoptosis in HepG2 human hepatoma cell line through extrinsic and intrinsic pathways: Involvement of P38 and ERK. Environ Toxicol Pharmacol. 40:847–854. 2015. View Article : Google Scholar : PubMed/NCBI
9	Ni F, Gong Y, Li L, Abdolmaleky HM and Zhou JR: Flavonoid ampelopsin inhibits the growth and metastasis of prostate cancer in vitro and in mice. PLoS One. 7:e388022012. View Article : Google Scholar : PubMed/NCBI
10	Liu T, Liu P, Ding F, Yu N, Li S, Wang S, Zhang X, Sun X, Chen Y, Wang F, et al: Ampelopsin reduces the migration and invasion of ovarian cancer cells via inhibition of epithelial-to-mesenchymal transition. Oncol Rep. 33:861–867. 2015. View Article : Google Scholar : PubMed/NCBI
11	Ruan LP, Yu BY, Fu GM and Zhu DN: Improving the solubility of ampelopsin by solid dispersions and inclusion complexes. J Pharm Biomed Anal. 38:457–464. 2005. View Article : Google Scholar : PubMed/NCBI
12	Zhang B, Dong S, Cen X, Wang X, Liu X, Zhang H, Zhao X and Wu Y: Ampelopsin sodium exhibits antitumor effects against bladder carcinoma in orthotopic xenograft models. Anticancer Drugs. 23:590–596. 2012. View Article : Google Scholar : PubMed/NCBI
13	Qin H: Study on preparation of high-water-soluble ampelopsin sodium and its anti-tumor effects (unpublished PhD thesis). Lanzhou University; 2006
14	Tada H, Shiho O, Kuroshima K, Koyama M and Tsukamoto K: An improved colorimetic assay for interleukin 2. J Immunol Methods. 93:157–165. 1986. View Article : Google Scholar : PubMed/NCBI
15	Cao SS and Zhen YS: Potentiation of antimetabolite antitumor activity in vivo by dipyridamole and amphotericin B. Cancer Chemother Pharmacol. 24:181–186. 1989. View Article : Google Scholar : PubMed/NCBI
16	Fernandez V, Hartmann E, Ott G, Campo E and Rosenwald A: Pathogenesis of mantle-cell lymphoma: All oncogenic roads lead to dysregulation of cell cycle and DNA damage response pathways. J Clin Oncol. 23:6364–6369. 2005. View Article : Google Scholar : PubMed/NCBI
17	Bisbis B, Delmas F, Joubès J, Sicard A, Hernould M, Inzé D, Mouras A and Chevalier C: Cyclin-dependent kinase (CDK) inhibitors regulate the CDK-cyclin complex activities in endoreduplicating cells of developing tomato fruit. J Biol Chem. 281:7374–7383. 2006. View Article : Google Scholar : PubMed/NCBI
18	Ford HL and Pardee AB: Cancer and the cell cycle. J Cell Biochem 32–33. (Suppl):166–172. 1999. View Article : Google Scholar
19	Nagasaka A, Kawane K, Yoshida H and Nagata S: Apaf-1-independent programmed cell death in mouse development. Cell Death Differ. 17:931–941. 2010. View Article : Google Scholar : PubMed/NCBI
20	Burgess DJ: Apoptosis: Refined and lethal. Nat Rev Cancer. 13:792013. View Article : Google Scholar : PubMed/NCBI
21	Annamalai P, Thayman M, Rajan S, Raman LS, Ramasubbu S and Perumal P: Ethyl acetate extract from marine sponge Hyattella cribriformis exhibit potent anticancer activity by promoting tubulin polymerization as evidenced mitotic arrest and induction of apoptosis. Pharmacogn Mag. 11:345–355. 2015. View Article : Google Scholar : PubMed/NCBI
22	Marko D, Kemény M, Bernady E, Habermeyer M, Weyand U, Meiers S, Frank O and Hofmann T: Studies on the inhibition of tumor cell growth and microtubule assembly by 3-hydroxy-4-[(E)-(2-furyl)methylidene]methyl-3-cyclopentene-1,2-dione, an intensively coloured Maillard reaction product. Food Chem Toxicol. 40:9–18. 2002. View Article : Google Scholar : PubMed/NCBI
23	Tong C, Fan HY, Chen DY, Song XF, Schatten H and Sun QY: Effects of MEK inhibitor U0126 on meiotic progression in mouse oocytes: Microtuble organization, asymmetric division and metaphase II arrest. Cell Res. 13:375–383. 2003. View Article : Google Scholar : PubMed/NCBI
24	Wilson L and Jordan MA: Microtubule dynamics-taking aim at a moving target. Chem Biol. 2:569–573. 1995. View Article : Google Scholar : PubMed/NCBI
25	Maushagen R, Reers S, Pfannerstill AC, Hahlbrock A, Stauber R, Rahmanzadeh R, Rades D, Pries R and Wollenberg B: Effects of paclitaxel on permanent head and neck squamous cell carcinoma cell lines and identification of anti-apoptotic caspase 9b. J Cancer Res Clin Oncol. 142:1261–1271. 2016. View Article : Google Scholar : PubMed/NCBI
26	Luo Y, Ji X, Liu J, Li Z, Wang W, Chen W, Wang J, Liu Q and Zhang X: Moderate intensity static magnetic fields affect mitotic spindles and increase the antitumor efficacy of 5-FU and taxol. Bioelectrochemistry. 109:31–40. 2016. View Article : Google Scholar : PubMed/NCBI
27	Chiu WH, Luo SJ, Chen CL, Cheng JH, Hsieh CY, Wang CY, Huang WC, Su WC and Lin CF: Vinca alkaloids cause aberrant ROS-mediated JNK activation, Mcl-1 downregulation, DNA damage, mitochondrial dysfunction, and apoptosis in lung adenocarcinoma cells. Biochem Pharmacol. 83:1159–1171. 2012. View Article : Google Scholar : PubMed/NCBI
28	Sun B, Wingate H, Swisher SG, Keyomarsi K and Hunt KK: Absence of pRb facilitates E2F1-induced apoptosis in breast cancer cells. Cell Cycle. 9:1122–1130. 2010. View Article : Google Scholar : PubMed/NCBI
29	Gamell C, Schofield AV, Suryadinata R, Sarcevic B and Bernard O: LIMK2 mediates resistance to chemotherapeutic drugs in neuroblastoma cells through regulation of drug-induced cell cycle arrest. PLoS One. 8:e728502013. View Article : Google Scholar : PubMed/NCBI
30	Wang X, Tanaka M, Krstin S, Peixoto HS and Wink M: The interference of selected cytotoxic alkaloids with the cytoskeleton: An insight into their modes of action. Molecules. 21:E9062016. View Article : Google Scholar : PubMed/NCBI
31	Giannakakou P, Sackett D and Fojo T: Tubulin/microtubules: Still a promising target for new chemotherapeutic agents. J Natl Cancer Inst. 92:182–183. 2000. View Article : Google Scholar : PubMed/NCBI
32	Davis A, Jiang JD, Middleton KM, Wang Y, Weisz I, Ling YH and Bekesi JG: Novel suicide ligands of tubulin arrest cancer cells in S-phase. Neoplasia. 1:498–507. 1999. View Article : Google Scholar : PubMed/NCBI
33	Komlodi-Pasztor E, Sackett D, Wilkerson J and Fojo T: Mitosis is not a key target of microtuble agents in patient tumors. Nat Rev Clin Oncol. 8:244–250. 2011. View Article : Google Scholar : PubMed/NCBI
34	Cheriyamundath S, Mahaddalkar T, Kantevari S and Lopus M: Induction of acetylation and bundling of cellular microtubules by 9-(4-vinylphenyl) noscapine elicits S-phase arrest in MDA-MB-231 cells. Biomed Pharmacotherapy. 86:74–80. 2017. View Article : Google Scholar
35	Blaqosklonny MV, Ginanakakou P, el-Deiry WS, Kingston DG, Higgs PI, Neckers L and Foji T: Raf-1/bcl-2 phosphorylatin: A step from microtuble damage to cell death. Cancer Res. 57:130–135. 1997.PubMed/NCBI
36	Mahaddalkar T, Mehta S, Cheriyamundath S, Muthurajan H and Lopus M: Tryptone-stabilized gold nanoparticles target tubulin and inhibit cell viability by inducing an unusual form of cell cycle arrest. Exp Cell Res. 360:163–170. 2017. View Article : Google Scholar : PubMed/NCBI
37	Li Y, Sun X, LaMont JT, Pardee AB and Li CJ: Selective killing of cancer cells by β-lapachone: Direct checkpoint activation as a strategy against cancer. PNAS. 100:2674–2678. 2003. View Article : Google Scholar : PubMed/NCBI