Alisol B 23‑acetate Inhibits the Viability and Induces Apoptosis of Non‑small Cell Lung Cancer Cells Via PI3K/AKT/mTOR Signal Pathway

Overview

Journal Mol Med Rep

Specialty Molecular Biology

Date 2019 Jun 8

PMID 31173235

Citations 9

Authors

Yang Liu

Xi-Chao Xia

Liu-Yang Meng

Yu Wang

Yue-Mei Li

Affiliations

Soon will be listed here.

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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References

Matsuda H, Kageura T, Toguchida I, Murakami T, Kishi A, 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. 1999; 9(21):3081-6. DOI: 10.1016/s0960-894x(99)00536-3. View

Hanahan D, Weinberg R . The hallmarks of cancer. Cell. 2000; 100(1):57-70. DOI: 10.1016/s0092-8674(00)81683-9. View

Martin K, Blenis J . Coordinate regulation of translation by the PI 3-kinase and mTOR pathways. Adv Cancer Res. 2002; 86:1-39. DOI: 10.1016/s0065-230x(02)86001-8. View

Mann J . Natural products in cancer chemotherapy: past, present and future. Nat Rev Cancer. 2003; 2(2):143-8. DOI: 10.1038/nrc723. View

Chaudhary U, Haldas J . Long-term complications of chemotherapy for germ cell tumours. Drugs. 2003; 63(15):1565-77. DOI: 10.2165/00003495-200363150-00004. View

Crowell J . The chemopreventive agent development research program in the Division of Cancer Prevention of the US National Cancer Institute: an overview. Eur J Cancer. 2005; 41(13):1889-910. DOI: 10.1016/j.ejca.2005.04.016. View

Huang Y, Huang D, Chueh S, Teng C, Guh J . 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. 2006; 231(2):270-8. DOI: 10.1016/j.canlet.2005.02.011. View

Jiang Z, Zhang X, Zhang F, Liu N, Zhao F, Zhou J . A new triterpene and anti-hepatitis B virus active compounds from Alisma orientalis. Planta Med. 2006; 72(10):951-4. DOI: 10.1055/s-2006-947178. View

Brouwers E, Huitema A, Beijnen J, Schellens J . Long-term platinum retention after treatment with cisplatin and oxaliplatin. BMC Clin Pharmacol. 2008; 8:7. PMC: 2559818. DOI: 10.1186/1472-6904-8-7. View

10.

Morgan T, Koreckij T, Corey E . Targeted therapy for advanced prostate cancer: inhibition of the PI3K/Akt/mTOR pathway. Curr Cancer Drug Targets. 2009; 9(2):237-49. PMC: 2921605. DOI: 10.2174/156800909787580999. View

11.

He C, Klionsky D . Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet. 2009; 43:67-93. PMC: 2831538. DOI: 10.1146/annurev-genet-102808-114910. View

12.

Law B, Wang M, Ma D, Al-Mousa F, Michelangeli F, Cheng S . Alisol B, a novel inhibitor of the sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase pump, induces autophagy, endoplasmic reticulum stress, and apoptosis. Mol Cancer Ther. 2010; 9(3):718-30. DOI: 10.1158/1535-7163.MCT-09-0700. View

13.

Foster K, Fingar D . Mammalian target of rapamycin (mTOR): conducting the cellular signaling symphony. J Biol Chem. 2010; 285(19):14071-7. PMC: 2863215. DOI: 10.1074/jbc.R109.094003. View

14.

Jin H, Jin Q, Kim A, Choi H, Lee J, Kim Y . A new triterpenoid from Alisma orientale and their antibacterial effect. Arch Pharm Res. 2012; 35(11):1919-26. DOI: 10.1007/s12272-012-1108-5. View

15.

Gutschner T, Hammerle M, Eissmann M, Hsu J, Kim Y, Hung G . The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res. 2012; 73(3):1180-9. PMC: 3589741. DOI: 10.1158/0008-5472.CAN-12-2850. View

16.

Surviladze Z, Sterk R, DeHaro S, Ozbun M . Cellular entry of human papillomavirus type 16 involves activation of the phosphatidylinositol 3-kinase/Akt/mTOR pathway and inhibition of autophagy. J Virol. 2012; 87(5):2508-17. PMC: 3571372. DOI: 10.1128/JVI.02319-12. View

17.

Lee A, Park J, Chun J, Moon B, Kang B, Seo Y . Optimization of Extraction Condition for Alisol B and Alisol B Acetate in Alismatis Rhizoma using Response Surface Methodology. J Liq Chromatogr Relat Technol. 2013; 36(4):513-524. PMC: 3545486. DOI: 10.1080/10826076.2012.668733. View

18.

Polivka Jr J, Janku F . Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway. Pharmacol Ther. 2013; 142(2):164-75. DOI: 10.1016/j.pharmthera.2013.12.004. View

19.

Xu W, Li T, Qiu J, Wu S, Huang M, Lin L . Anti-proliferative activities of terpenoids isolated from Alisma orientalis and their structure-activity relationships. Anticancer Agents Med Chem. 2014; 15(2):228-35. DOI: 10.2174/1871520614666140601213514. View

20.

Melo-Lima S, Lopes M, Mollinedo F . ERK1/2 acts as a switch between necrotic and apoptotic cell death in ether phospholipid edelfosine-treated glioblastoma cells. Pharmacol Res. 2015; 95-96:2-11. DOI: 10.1016/j.phrs.2015.02.007. View