Andrographolide Inhibits Proliferation and Promotes Apoptosis in Bladder Cancer Cells by Interfering with NF-κB and PI3K/AKT Signaling <italic style="font-style: italic">In Vitro</italic> and <italic style="font-style: italic">In Vivo</italic>

Lei XUAN; Jing-hai HU; Ran BI; Si-qi LIU; Chun-xi WANG

doi:10.1007/s11655-022-3464-4

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Andrographolide Inhibits Proliferation and Promotes Apoptosis in Bladder Cancer Cells by Interfering with NF-κB and PI3K/AKT Signaling In Vitro and In Vivo

Original Article | Updated：2022-03-29

- Andrographolide Inhibits Proliferation and Promotes Apoptosis in Bladder Cancer Cells by Interfering with NF-κB and PI3K/AKT Signaling In Vitro and In Vivo
- Andrographolide Inhibits Proliferation and Promotes Apoptosis in Bladder Cancer Cells by Interfering with NF-κB and PI3K/AKT Signaling In Vitro and In Vivo
- Chinese Journal of Integrative Medicine 2022年28卷第4期页码：349-356
- Affiliations：
  
  Department of Urology, the First Hospital of Jilin University,Changchun (130021), China
- Author bio：
  
  Prof. WANG Chun-xi, E-mail: chunxi@jlu.edu.cn
- Funds：
  
  Science and Technology Department of Jilin Province(20190905001SF)
- DOI：10.1007/s11655-022-3464-4
  中图分类号：
- 纸质出版日期：2022-04，
  
  网络出版日期：2022-01-19，
  
  录用日期：2021-06-11
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Lei XUAN, Jing-hai HU, Ran BI, 等. Andrographolide Inhibits Proliferation and Promotes Apoptosis in Bladder Cancer Cells by Interfering with NF-κB and PI3K/AKT Signaling In Vitro and In Vivo[J]. Chinese Journal of Integrative Medicine, 2022,28(4):349-356.

Lei XUAN, Jing-hai HU, Ran BI, et al. Andrographolide Inhibits Proliferation and Promotes Apoptosis in Bladder Cancer Cells by Interfering with NF-κB and PI3K/AKT Signaling In Vitro and In Vivo[J]. Chinese Journal of Integrative Medicine, 2022,28(4):349-356.
Lei XUAN, Jing-hai HU, Ran BI, 等. Andrographolide Inhibits Proliferation and Promotes Apoptosis in Bladder Cancer Cells by Interfering with NF-κB and PI3K/AKT Signaling In Vitro and In Vivo[J]. Chinese Journal of Integrative Medicine, 2022,28(4):349-356. DOI： 10.1007/s11655-022-3464-4.

Lei XUAN, Jing-hai HU, Ran BI, et al. Andrographolide Inhibits Proliferation and Promotes Apoptosis in Bladder Cancer Cells by Interfering with NF-κB and PI3K/AKT Signaling In Vitro and In Vivo[J]. Chinese Journal of Integrative Medicine, 2022,28(4):349-356. DOI： 10.1007/s11655-022-3464-4.

摘要

目的:

探索穿心莲内酯对膀胱癌细胞和荷人膀胱癌原位移植瘤小鼠模型的影响.

方法:

在体外实验中

用0-40 μmol/L穿心莲内酯处理T24细胞

用0-80 μmol/L穿心莲内酯处理5637细胞. 使用CCK-8、成克隆实验、划痕实验和transwell测定法评估膀胱癌细胞的生长、迁移和浸润. 使用流式细胞术测定膀胱癌细胞凋亡情况. 在体内研究中

通过5637膀胱癌细胞系构建荷人膀胱癌原位移植瘤小鼠模型评估了穿心莲内酯(10 mg/kg)的抗肿瘤作用

并通过免疫印迹法测定了NF-κB和PI3K/AKT相关蛋白的水平.

结果:

穿心莲内酯抑制膀胱癌细胞的生长、迁移和浸润 (

0.05 或

0.01) . 穿心莲内酯在膀胱癌细胞系中诱导了内在的线粒体依赖性细胞凋亡. 另一方面

穿心莲内酯抑制小鼠体内膀胱癌细胞的生长 (

0.01) . 在体外和体内实验中

穿心莲内酯均抑制了p65、p-AKT的表达 (

0.05或

0.01) .

Abstract

Objective:

To explore the inﬂuences of andrographolide (Andro) on bladder cancer cell lines and a tumor xenograft mouse model bearing 5637 cells.

Methods:

For

in vitro

experiments

T24 cells were stimulated with Andro (0–40 μmol/L) and 5637 cells were stimulated with Andro (0 to 80 μmol/L). Cell growth

migration

and infiltration were assessed using cell counting kit-8

colony formation

wound healing

and transwell assays. Apoptosis rate was examined using ﬂow cytometry. In

in vivo

study

the antitumor effect of Andro (10 mg/kg) was evaluated by 5637 tumor-bearing mice

and levels of nuclear factor κB (NF-κB) and phosphoinositide 3-kinase/AKT related-proteins were determined by immunoblotting.

Results:

Andro suppressed growth

migration

and infiltraion of bladder cancer cells (

≤0.05 or

≤ 0.01). Additionally

Andro induced intrinsic mitochondria-dependent apoptosis in bladder cancer cell lines. Furthermore

Andro inhibited bladder cancer growth in mice (

≤0.01). The expression of p65

p-AKT were suppressed by Andro treatment

in vitro

and

in vivo

(

≤ 0.05 or

≤ 0.01).

Conclusions:

Andrographolide inhibits proliferation and promotes apoptosis in bladder cancer cells by interfering with NF-κB and PI3K/AKT signaling

in vitro

and

in vivo

关键词

Keywords

andrographolideChinese medicinebladder cancernuclear factor κBPI3K-AKT

references

Afshari M, Janbabaei G, Bahrami MA, Moosazadeh M.Opium and bladder cancer: a systematic review and meta-analysis of the odds ratios for opium use and the risk of bladder cancer. PLoS One 2017;12:e0178527.

Svatek RS, Hollenbeck BK, Holmäng S, Lee R, Kim SP, Stenzl A,et al. The economics of bladder cancer: costs and considerations of caring for this disease. Eur Urol 2014;66:253-262.

Antoni S, Ferlay J, Soerjomataram I, Znaor A, Jemal A,Bray F. Bladder cancer incidence and mortality: a global overview and recent trends. Eur Urol 2017;71:96-108.

Wu P, Meng X, Zheng H, Zeng Q, Chen T, Wang W, et al. Kaempferol attenuates ROS-induced hemolysis and the molecular mechanism of its induction of apoptosis on bladder cancer. Molecules 2018;23:2592.

Low M, Khoo CS, Münch G, Govindaraghavan S, Sucher NJ. An in vitro study of anti-inflammatory activity of standardised Andrographis paniculata extracts and pure andrographolide. BMC Complement Altern Med 2015;15:18.

Yang PY, Hsieh PL, Wang TH, Yu CC, Lu MY, Liao YW,et al. Andrographolide impedes cancer stemness and enhances radio-sensitivity in oral carcinomas via miR-218 activation. Oncotarget 2017;8:4196-4207.

Gunn EJ, Williams JT, Huynh DT, Iannotti MJ, Han C,Barrios FJ, et al. The natural products parthenolide and andrographolide exhibit anti-cancer stem cell activity in multiple myeloma. Leuk Lymphoma 2011;52:1085-1097.

Kumar D, Kumar S, Gorain M, Tomar D, Patil HS, Radharani NNV, et al. Notch1-MAPK signaling axis regulates CD133(+) cancer stem cell-mediated melanoma growth and angiogenesis. J Invest Dermatol 2016;136:2462-2474.

Lee YC, Lin HH, Hsu CH, Wang CJ, Chiang TA, Chen JH Inhibitory effects of andrographolide on migration and invasion in human non-small cell lung cancer A549 cells via down-regulation of PI3K/Akt signaling pathway. Eur J Pharmacol 2010;632:23-32.

Deng Y, Bi R, Guo H, Yang J, Du Y, Wang C, et al.Andrographolide enhances TRAIL-induced apoptosis via p53-mediated death receptors up-regulation and suppression of the NF-κB pathway in bladder cancer cells.Int J Biol Sci 2019;15:688-700.

Sanchez-Vega F, Mina M, Armenia J, Chatila WK, Luna A,La KC, et al. Oncogenic signaling pathways in the cancer genome atlas. Cell 2018;173:321-337.e10.

Luo K. Signaling cross talk between TGF-β/Smad and other signaling pathways. Cold Spring Harb Perspect Biol 2017;9:022137.

Gilmore TD. Introduction to NF-kappaB: players, pathways,perspectives. Oncogene 2006;25:6680-6684.

Mussard E, Cesaro A, Lespessailles E, Legrain B, Berteina-Raboin S, Toumi H. Andrographolide, a natural antioxidant:an update. Antioxidants (Basel) 2019;8:571.

Chu J, Li N, Li F. A risk score staging system based on the expression of seven genes predicts the outcome of bladder cancer. Oncol Lett 2018;16:2091-2096.

Sun J. Matrix metalloproteinases and tissue inhibitor of metalloproteinases are essential for the inflammatory response in cancer cells. J Signal Transduct 2010;2010:985132.

Annibaldi A, Walczak H. Death receptors and their ligands in inflammatory disease and cancer. Cold Spring Harb Perspect Biol 2020;12:a036384.

Krammer PH. CD95's deadly mission in the immune system. Nature 2000;407:789-795.

Gurunathan S, Qasim M, Park CH, Arsalan Iqbal M, Yoo H,Hwang JH, et al. Cytotoxicity and transcriptomic analyses of biogenic palladium nanoparticles in human ovarian cancer cells (SKOV3). Nanomaterials (Basel) 2019;9:787.

Czabotar PE, Lessene G, Strasser A, Adams JM. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol 2014;15:49-63.

Jain MV, Paczulla AM, Klonisch T, Dimgba FN, Rao SB,Roberg K, et al. Interconnections between apoptotic,autophagic and necrotic pathways: implications for cancer therapy development. J Cell Mol Med 2013;17:12-29.

Peng S, Hang N, Liu W, Guo W, Jiang C, Yang X, et al.Andrographolide sulfonate ameliorates lipopolysaccharide-induced acute lung injury in mice by down-regulating MAPK and NF-κB pathways. Acta Pharm Sin B 2016;6:205-211.

Zhu T, Wang DX, Zhang W, Liao XQ, Guan X, Bo H, et al.Andrographolide protects against LPS-induced acute lung injury by inactivation of NF-κB. PLoS One 2013;8:e56407.

Chakraborty S, Ehsan I, Mukherjee B, Mondal L, Roy S,Saha KD, et al. Therapeutic potential of andrographolide-loaded nanoparticles on a murine asthma model.Nanomedicine 2019;20:102006.

Liu YH, Zhang ZB, Zheng YF, Chen HM, Yu XT, Chen XY,et al. Gastroprotective effect of andrographolide sodium bisulfite against indomethacin-induced gastric ulceration in rats. Int Immunopharmacol 2015;26:384-391.

Burgos RA, Alarcón P, Quiroga J, Manosalva C,Hancke J.Andrographolide, an anti-inflammatory multitarget drug: all roads lead to cellular metabolism. Molecules 2020;26:5.

Jaiswal PK, Goel A, Mittal RD. Survivin: a molecular biomarker in cancer. Indian J Med Res 2015;141:389-397.

Wheatley SP, Altieri DC. Survivin at a glance. J Cell Sci 2019;132:jcs223826.

Bansal K, Kapoor N, Narayana Y, Puzo G, Gilleron M,Balaji KN. PIM2 Induced COX-2 and MMP-9 expression in macrophages requires PI3K and Notch1 signaling. PLoS One 2009;4:e4911.

Chen J. The cell-cycle arrest and apoptotic functions of p53 in tumor initiation and progression. Cold Spring Harb Perspect Med 2016;6:a026104.

Brenner D, Mak TW. Mitochondrial cell death effectors.Curr Opin Cell Biol 2009;21:871-877.

Minhajuddin M, Bijli KM, Fazal F, Sassano A, Nakayama KI,Hay N, et al. Protein kinase C-delta and phosphatidylinositol 3-kinase/Akt activate mammalian target of rapamycin to modulate NF-kappaB activation and intercellular adhesion molecule-1 (ICAM-1) expression in endothelial cells. J Biol Chem 2009; 284:4052-4061.

Chen D, Liu D, Liu D, He M, Peng A, Xu J, et al. Rheumatoid arthritis fibroblast-like synoviocyte suppression mediated by PTEN involves survivin gene silencing. Sci Rep 2017;7:367.

Chen X, Duan N, Zhang C, Zhang W. Survivin and tumorigenesis: molecular mechanism stumorigenesis:molecular mechanisms and therapeutic strategies. J Cancer 2016;7:314-323.

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Andrographolide Inhibits Proliferation and Promotes Apoptosis in Bladder Cancer Cells by Interfering with NF-κB and PI3K/AKT Signaling In Vitro and In Vivo

Andrographolide Inhibits Proliferation and Promotes Apoptosis in Bladder Cancer Cells by Interfering with NF-κB and PI3K/AKT Signaling In Vitro and In Vivo

DOI：10.1007/s11655-022-3464-4

摘要

Abstract

关键词

Keywords

references