Alisol B 23‑acetate inhibits the viability and induces apoptosis of non‑small cell lung cancer cells via PI3K/AKT/mTOR signal pathway

Liu,Yang; Xia,Xi‑Chao; Meng,Liu‑Yang; Wang,Yu; Li,Yue‑Mei

doi:10.3892/mmr.2019.10355

Alisol B 23‑acetate inhibits the viability and induces apoptosis of non‑small cell lung cancer cells via PI3K/AKT/mTOR signal pathway

Authors:
- Yang Liu
- Xi‑Chao Xia
- Liu‑Yang Meng
- Yu Wang
- Yue‑Mei Li
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Affiliations: Department of Medicine, Pingdingshan University, Pingdingshan, Henan 467000, P.R. China, Emergency Department, Pingdingshan Second People's Hospital, Pingdingshan, Henan 467000, P.R. China
Published online on: June 6, 2019 https://doi.org/10.3892/mmr.2019.10355
Pages: 1187-1195
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to investigate the effects of alisol B 23‑acetate (AB23A) on inhibiting the viability and inducing apoptosis of human non‑small cell lung cancer (NSCLC) cells and the anticancer mechanisms of AB23A in vitro. The viability of A549 cells following treatment with different doses of AB23A was examined using a Cell Counting Kit‑8 assay. Subsequently, apoptosis and the cell cycle were detected using flow cytometric analysis. The effect of AB23A on migration and invasion of A549 cells was detected by wound healing and Transwell assays. Western blotting was performed to determine the relative expression of Bax/Bcl‑2, phosphatidylinositol 3‑kinase (PI3K), protein kinase B (AKT) and mammalian target of rapamycin (mTOR). AB23A markedly inhibited the viability enhanced apoptosis of A549 cells and arrested the cell cycle in G1 phase. Additionally, AB23A upregulated the ratio of Bax/Bcl‑2 in the A549 cells in a concentration‑dependent manner. The results of wound healing and Transwell assays indicated that AB23A also suppresses the migration and invasion ability of A549 cells. Furthermore, AB23A reduced the protein levels of phosphorylated AKT, PI3K and mTOR. In conclusion, AB23A exerted anti‑cancer activity via inhibiting cells viability, migration and invasion, and promoting apoptosis. Therefore, AB23A is a potential antitumor drug for the treatment of NSCLC.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI
2	Chaudhary UB and Haldas JR: Long-term complications of chemotherapy for germ cell tumours. Drugs. 63:1565–1577. 2003. View Article : Google Scholar : PubMed/NCBI
3	Brouwers EE, Huitema AD, Beijnen JH and Schellens JH: Long-term platinum retention after treatment with cisplatin and oxaliplatin. BMC Clin Pharmacol. 8:72008. View Article : Google Scholar : PubMed/NCBI
4	Huang YT, Huang DM, Chueh SC, Teng CM and Guh JH: Alisol B acetate, a triterpene from Alismatis rhizoma, induces Bax nuclear translocation and apoptosis in human hormone-resistant prostate cancer PC-3 cells. Cancer Lett. 231:270–278. 2006. View Article : Google Scholar : PubMed/NCBI
5	Oral O, Akkoc Y, Bayraktar O and Gozuacik D: Physiological and pathological significance of the molecular cross-talk between autophagy and apoptosis. Histol Histopathol. 31:479–498. 2016.PubMed/NCBI
6	Crowell JA: The chemopreventive agent development research program in the Division of Cancer Prevention of the US National Cancer Institute: An overview. Eur J Cancer. 41:1889–1910. 2005. View Article : Google Scholar : PubMed/NCBI
7	Mann J: Natural products in cancer chemotherapy: Past, present and future. Nat Rev Cancer. 2:143–148. 2002. View Article : Google Scholar : PubMed/NCBI
8	Lee AY, Park JY, Chun JM, Moon BC, Kang BK, Seo YB, Shin HK and Kim HK: Optimization of extraction condition for alisol B and alisol B acetate in alismatis rhizoma using response surface methodology. J Liq Chromatogr Relat Technol. 36:513–524. 2013. View Article : Google Scholar : PubMed/NCBI
9	Law BY, Wang M, Ma DL, Al-Mousa F, Michelangeli F, Cheng SH, Ng MH, To KF, Mok AY, Ko RY, et al: Alisol B, a novel inhibitor of the sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase pump, induces autophagy, endoplasmic reticulum stress, and apoptosis. Mol Cancer Ther. 9:718–730. 2010. View Article : Google Scholar : PubMed/NCBI
10	Xu W, Li T, Qiu JF, Wu SS, Huang MQ, Lin LG, Zhang QW, Chen XP and Lu JJ: Anti-proliferative activities of terpenoids isolated from Alisma orientalis and their structure-activity relationships. Anticancer Agents Med Chem. 15:228–235. 2015. View Article : Google Scholar : PubMed/NCBI
11	Jiang ZY, Zhang XM, Zhang FX, Liu N, Zhao F, Zhou J and Chen JJ: A New triterpene and anti-hepatitis B virus active compounds from Alisma orientalis. Planta Med. 72:951–954. 2006. View Article : Google Scholar : PubMed/NCBI
12	Jin HG, Jin Q, Ryun Kim A, Choi H, Lee JH, Kim YS, Lee DG and Woo ER: A new triterpenoid from Alisma orientale and their antibacterial effect. Arch Pharm Res. 35:1919–1926. 2012. View Article : Google Scholar : PubMed/NCBI
13	Wang C, Feng L, Ma L, Chen H, Tan X, Hou X, Song J, Cui L, Liu D, Chen J, et al: Alisol a 24-acetate and alisol B 23-acetate induced autophagy mediates apoptosis and nephrotoxicity in human renal proximal tubular cells. Front Pharmacol. 8:1722017.PubMed/NCBI
14	Xiong Y, Huang BY and Yin JY: Pharmacogenomics of platinum-based chemotherapy in non-small cell lung cancer: Focusing on DNA repair systems. Med Oncol. 34:482017. View Article : Google Scholar : PubMed/NCBI
15	Yang L, Yang C, Li C, Zhao Q, Liu L, Fang X and Chen XY: Recent advances in biosynthesis of bioactive compounds in traditional Chinese medicinal plants. Sci Bull (Beijing). 61:3–17. 2016. View Article : Google Scholar : PubMed/NCBI
16	Xu W, Li X, Lin N, Zhang X, Huang X, Wu T, Tai Y, Chen S, Wu CH, Huang M and Wu S: Pharmacokinetics and tissue distribution of five major triterpenoids after oral administration of Rhizoma Alismatis extract to rats using ultra high-performance liquid chromatography-tandem mass spectrometry. J Pharm Biomed Anal. 146:314–323. 2017. View Article : Google Scholar : PubMed/NCBI
17	Zhang X, Li XY, Lin N, Zhao WL, Huang XQ, Chen Y, Huang MQ, Xu W and Wu SS: Diuretic activity of compatible triterpene components of alismatis rhizoma. Molecules. 22(pii): E14592017. View Article : Google Scholar : PubMed/NCBI
18	Matsuda H, Kageura T, Toguchida I, Murakami T, Kishi A and Yoshikawa M: Effects of sesquiterpenes and triterpenes from the rhizome of Alisma orientale on nitric oxide production in lipopolysaccharide-activated macrophages: Absolute stereostructures of alismaketones-B 23-acetate and -C 23-acetate. Bioorg Med Chem Lett. 9:3081–3086. 1999. View Article : Google Scholar : PubMed/NCBI
19	Zhang A, Sheng Y and Zou M: Antiproliferative activity of Alisol B in MDA-MB-231 cells is mediated by apoptosis, dysregulation of mitochondrial functions, cell cycle arrest and generation of reactive oxygen species. Biomed Pharmacother. 87:110–1107. 2017. View Article : Google Scholar : PubMed/NCBI
20	Zhang LL, Xu YL, Tang ZH, Xu XH, Chen X, Li T, Ding CY, Huang MQ, Chen XP, Wang YT, et al: Effects of alisol B 23-acetate on ovarian cancer cells: G1 phase cell cycle arrest, apoptosis, migration and invasion inhibition. Phytomedicine. 23:800–809. 2016. View Article : Google Scholar : PubMed/NCBI
21	Melo-Lima S, Lopes MC and Mollinedo F: ERK1/2 acts as a switch between necrotic and apoptotic cell death in ether phospholipid edelfosine-treated glioblastoma cells. Pharmacol Res. 95-96:2–11. 2015. View Article : Google Scholar : PubMed/NCBI
22	Zhao Y, Li ETS and Wang M: Alisol B 23-acetate induces autophagic-dependent apoptosis in human colon cancer cells via ROS generation and JNK activation. Oncotarget. 8:70239–70249. 2017.PubMed/NCBI
23	Hanahan D and Weinberg RA: The hallmarks of cancer. Cell. 100:57–70. 2000. View Article : Google Scholar : PubMed/NCBI
24	Fujimura K, Choi S, Wyse M, Strnadel J, Wright T and Klemke R: Eukaryotic translation initiation factor 5A (EIF5A) regulates pancreatic cancer metastasis by modulating RhoA and Rho-associated kinase (ROCK) protein expression levels. J Biol Chem. 290:29907–29919. 2015. View Article : Google Scholar : PubMed/NCBI
25	Gutschner T, Hämmerle M, Eissmann M, Hsu J, Kim Y, Hung G, Revenko A, Arun G, Stentrup M, Gross M, et al: The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res. 73:1180–1189. 2013. View Article : Google Scholar : PubMed/NCBI
26	Morgan TM, Koreckij TD and Corey E: Targeted therapy for advanced prostate cancer: Inhibition of the PI3K/Akt/mTOR pathway. Curr Cancer Drug Targets. 9:237–249. 2009. View Article : Google Scholar : PubMed/NCBI
27	Martin KA and Blenis J: Coordinate regulation of translation by the PI 3-kinase and mTOR pathways. Adv Cancer Res. 86:1–39. 2002. View Article : Google Scholar : PubMed/NCBI
28	Surviladze Z, Sterk RT, DeHaro SA and Ozbun MA: Cellular entry of human papillomavirus type 16 involves activation of the phosphatidylinositol 3-kinase/Akt/mTOR pathway and inhibition of autophagy. J Virol. 87:2508–2517. 2013. View Article : Google Scholar : PubMed/NCBI
29	Foster KG and Fingar DC: Mammalian target of rapamycin (mTOR): Conducting the cellular signaling symphony. J Biol Chem. 285:14071–14077. 2010. View Article : Google Scholar : PubMed/NCBI
30	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
31	Yu W, Sun H, Zha W, Cui W, Xu L, Min Q and Wu J: Apigenin attenuates adriamycin-induced cardiomyocyte apoptosis via the PI3K/AKT/mTOR pathway. Evid Based Complement Alternat Med. 2017:25906762017. View Article : Google Scholar : PubMed/NCBI
32	Yang J, Pi C and Wang G: Inhibition of PI3K/Akt/mTOR pathway by apigenin induces apoptosis and autophagy in hepatocellular carcinoma cells. Biomed Pharmacother. 103:699–707. 2018. View Article : Google Scholar : PubMed/NCBI
33	Polivka J Jr and Janku F: Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway. Pharmacol Ther. 142:164–175. 2014. View Article : Google Scholar : PubMed/NCBI