Molecular mechanisms of apoptosis and autophagy elicited by combined treatment with oridonin and cetuximab in laryngeal squamous cell carcinoma.
Animals
Antineoplastic Combined Chemotherapy Protocols
/ metabolism
Apoptosis
/ drug effects
Autophagy
/ drug effects
Carcinoma, Squamous Cell
/ drug therapy
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cetuximab
/ administration & dosage
Diterpenes, Kaurane
/ administration & dosage
Drug Synergism
Humans
Laryngeal Neoplasms
/ drug therapy
Mice
Mice, Nude
Reactive Oxygen Species
/ metabolism
Signal Transduction
/ drug effects
Xenograft Model Antitumor Assays
Apoptosis
Autophagy
Cetuximab
Laryngeal squamous cell carcinoma
Oridonin
Journal
Apoptosis : an international journal on programmed cell death
ISSN: 1573-675X
Titre abrégé: Apoptosis
Pays: Netherlands
ID NLM: 9712129
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
pubmed:
16
11
2018
medline:
21
4
2020
entrez:
16
11
2018
Statut:
ppublish
Résumé
Combined oridonin (ORI), a natural and safe kaurene diterpenoid isolated from Rabdosia rubescens, and cetuximab (Cet), an anti-EGFR monoclonal antibody, have been reported to exert synergistic anti-tumor effects against laryngeal squamous cell carcinoma (LSCC) both in vitro and in vivo by our group. In the present study, we further found that ORI/Cet treatment not only resulted in apoptosis but also induced autophagy. AMPK/mTOR signaling pathway was found to be involved in the activation of autophagy in ORI/Cet-treated LSCC cells, which is independent of p53 status. Additionally, chromatin immunoprecipitation (ChIP) assay showed that ORI/Cet significantly increased the binding NF-κB family member p65 with the promotor of BECN 1, and p65-mediated up-regulation of BECN 1 caused by ORI/Cet is coupled to increased autophagy. On the other hand, we demonstrated that either Beclin 1 SiRNA or autophagy inhibitors could increase ORI/Cet induced-apoptosis, indicating that autophagy induced by combination of the two agents plays a cytoprotective role. Interestingly, 48 h after the combined treatment, autophagy began to decrease but apoptosis was significantly elevated. Our findings suggest that autophagy might be strongly associated with the antitumor efficacy of ORI/Cet, which may be beneficial to the clinical application of ORI/Cet in LSCC treatment.
Identifiants
pubmed: 30430397
doi: 10.1007/s10495-018-1497-0
pii: 10.1007/s10495-018-1497-0
doi:
Substances chimiques
Diterpenes, Kaurane
0
Reactive Oxygen Species
0
oridonin
0APJ98UCLQ
Cetuximab
PQX0D8J21J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
33-45Subventions
Organisme : National Natural Science Foundation of China
ID : 81373797
Pays : International
Organisme : National Natural Science Foundation of China
ID : 81102855
Pays : International
Organisme : China postdoctoral Science Special Foundation
ID : 2014T70224
Pays : International
Organisme : China Postdoctoral Science Foundation
ID : 2013M541192
Pays : International
Références
Codogno P, Meijer AJ (2005) Autophagy and signaling: their role in cell survival and cell death. Cell Death Differ 12:1509–1518
doi: 10.1038/sj.cdd.4401751
pubmed: 16247498
Chen N, Karantza V (2011) Autophagy as a therapeutic target in cancer. Cancer Biol Ther 11:157–168
doi: 10.4161/cbt.11.2.14622
pubmed: 21228626
pmcid: 3230307
Zeng X, Kinsella TJ (2011) Impact of autophagy on chemotherapy and radiotherapy mediated tumor cytotoxicity: “To Live or not to Live”. Front Oncol 1:30
doi: 10.3389/fonc.2011.00030
pubmed: 22655239
pmcid: 3356061
Zhang H, Tang J, Li C, Kong J et al (2015) MiR-22 regulates 5-FU sensitivity by inhibiting autophagy and promoting apoptosis in colorectal cancer cells. Cancer Lett 356:781–790
doi: 10.1016/j.canlet.2014.10.029
pubmed: 25449431
Gong C, Song E, Codogno P et al (2012) The roles of BECN1 and autophagy in cancer are context dependent. Autophagy 8:1853–1855
doi: 10.4161/auto.21996
pubmed: 22960473
pmcid: 3541303
Shinojima N, Yokoyama T, Kondo Y et al (2007) Roles of the Akt/mTOR/p70S6K and ERK1/2 signaling pathways in curcumin-induced autophagy. Autophagy 3:635–637
doi: 10.4161/auto.4916
pubmed: 17786026
Wu Y, Ni Z, Yan X et al (2016) Targeting the MIR34C-5p-ATG4B- autophagy axis enhances the sensitivity of cervical cancer cells to pirarubicin. Autophagy 12:1105–1117
doi: 10.1080/15548627.2016.1173798
pubmed: 27097054
pmcid: 4990997
Kozyreva VK, Kiseleva A, Ice RJ et al (2016) Combination of eribulin and aurora A inhibitor MLN8237 prevents metastatic colonization and induces cytotoxic autophagy in breast cancer. Mol Cancer Ther 15:1809–1822
doi: 10.1158/1535-7163.MCT-15-0688
pubmed: 27235164
pmcid: 4975626
Yang ZJ, Chee CE, Huang S et al (2011) The role of autophagy in cancer: therapeutic implications. Mol Cancer Ther 10:1533–1541
doi: 10.1158/1535-7163.MCT-11-0047
pubmed: 21878654
pmcid: 3170456
Kumar D, Shankar S, Srivastava RK (2014) Rottlerin induces autophagy and apoptosis in prostate cancer stem cells via PI3K/Akt/mTOR signaling pathway. Cancer Lett 343:179–189
doi: 10.1016/j.canlet.2013.10.003
pubmed: 24125861
Green AS, Chapuis N, Lacombe C et al (2011) LKB1/AMPK/mTOR signaling pathway in hematological malignancies: from metabolism to cancer cell biology. Cell Cycle 10:2115–2120
doi: 10.4161/cc.10.13.16244
pubmed: 21572254
Arsikin K, Kravic-Stevovic T, Jovanovic M et al (2012) Autophagy-dependent and -independent involvement of AMP-activated protein kinase in 6-hydroxydopamine toxicity to SH-SY5Y neuroblastoma cells. Biochim Biophys Acta 1822:1826–1836
doi: 10.1016/j.bbadis.2012.08.006
pubmed: 22917563
Jing K, Song KS, Shin S et al (2011) Docosahexaenoic acid induces autophagy through p53/AMPK/mTOR signaling and promotes apoptosis in human cancer cells harboring wild-type p53. Autophagy 7:1348–1358
doi: 10.4161/auto.7.11.16658
pubmed: 21811093
pmcid: 3242799
Niso-santano M, Criollo A, Malik SA et al (2012) Direct molecular interactions between Beclin 1 and the canonical NFκB activation pathway. Autophagy 8:268–270
doi: 10.4161/auto.8.2.18845
pubmed: 22301997
Harris J (2011) Autophagy and cytokines. Cytokine 56:140–144
doi: 10.1016/j.cyto.2011.08.022
pubmed: 21889357
Kiyono K, Suzuki HI, Matsuyama H et al (2009) Autophagy is activated by TGF-beta and potentiates TGF-beta-mediated growth inhibition in human hepatocellular carcinoma cells. Cancer Res 69:8844–8852
doi: 10.1158/0008-5472.CAN-08-4401
pubmed: 19903843
Jiang Q, Wang Y, Li T et al (2011) Heat shock protein 90-mediated inactivation of nuclear factor-kappaB switches autophagy to apoptosis through becn1 transcriptional inhibition in selenite-induced NB4 cells. Mol Biol Cell 22:1167–1180
doi: 10.1091/mbc.e10-10-0860
pubmed: 21346199
pmcid: 3078072
Ran W, Qian Z, Xin P et al (2016) Stellettin B induces G1 arrest, apoptosis and autophagy in human non-small cell lung cancer A549 cells via blocking PI3K/Akt/mTOR pathway. Sci Rep 6:27071
doi: 10.1038/srep27071
D’Anneo A, Carlisi D, Lauricella M et al (2013) Parthenolide generates reactive oxygen species and autophagy in MDA-MB231 cells. A soluble parthenolide analogue inhibits tumour growth and metastasis in a xenograft model of breast cancer. Cell Death Dis 4:e891
doi: 10.1038/cddis.2013.415
pubmed: 24176849
pmcid: 3920954
Li CY, Wang EQ, Cheng Y et al (2011) Oridonin: An active diterpenoid targeting cell cycle arrest, apoptotic and autophagic pathways for cancer therapeutics. Int J Biochem Cell Biol 43:701–704
doi: 10.1016/j.biocel.2011.01.020
pubmed: 21295154
Cui Q, Tashiro S, Onodera S et al (2007) Autophagy preceded apoptosis in oridonin-treated human breast cancer MCF-7 cells. Biol Pharm Bull 30:859–864
doi: 10.1248/bpb.30.859
pubmed: 17473426
Kang N, Zhang JH, Qiu F et al (2010) Inhibition of EGFR signaling augments oridonin-induced apoptosis in human laryngeal cancer cells via enhancing oxidative stress coincident with activation of both the intrinsic and extrinsic apoptotic pathways. Cancer Lett 294:147–158
doi: 10.1016/j.canlet.2010.01.032
Zhang Y, Wu Y, Tashiro S et al (2009) Involvement of PKC signal pathways in oridonin-induced autophagy in HeLa cells: a protective mechanism against apoptosis. Biochem Biophys Res Commun 378:273–278
doi: 10.1016/j.bbrc.2008.11.038
pubmed: 19026988
Kang N, Cao SJ, Zhou Y et al (2015) Inhibition of caspase-9 by oridonin, a diterpenoid isolated from Rabdosia rubescens, augments apoptosis in human laryngeal cancer cells. Int J Oncol 47:2045–2056
doi: 10.3892/ijo.2015.3186
pubmed: 26648189
pmcid: 4665153
Cui Q, Tashiro S, Onodera S et al (2006) Augmentation of oridonin-induced apoptosis observed with reduced autophagy. J Pharmacol Sci 101:230–239
doi: 10.1254/jphs.FPJ06003X
pubmed: 16861822
Ng K, Zhu AX (2008) Targeting the epidermal growth factor receptor in metastatic colorectal cancer. Crit Rev Oncol Hematol 65:8–20
doi: 10.1016/j.critrevonc.2007.09.006
pubmed: 18006328
Cao SJ, Xia MJ, Mao YW et al (2016) Combined oridonin with cetuximab treatment shows synergistic anticancer effects on laryngeal squamous cell carcinoma: involvement of inhibition of EGFR and activation of reactive oxygen species-mediated JNK pathway. Int J Oncol 49:2075–2087
doi: 10.3892/ijo.2016.3696
pubmed: 27667173
Saik S, Sasazawa Y, Imamichi Y et al (2011) Caffeine induces apoptosis by enhancement of autophagy via PI3K/Akt/mTOR/p70S6K inhibition. Autophagy 7:176–187
doi: 10.4161/auto.7.2.14074
Lu F, Kishida S, Mu P et al (2015) NeuroD1 promotes neuroblastoma cell growth by inducing the expression of ALK. Cancer Sci 106:390–396
doi: 10.1111/cas.12628
pubmed: 25652313
pmcid: 4409882
Rosenfeldt MT, Ryan KM (2011) The multiple roles of autophagy in cancer. Carcinogenesis 32:955–963
doi: 10.1093/carcin/bgr031
pubmed: 21317301
pmcid: 3128556
Wang X, Hao MW, Dong K et al (2009) Apoptosis induction effects of EGCG in laryngeal squamous cell carcinoma cells through telomerase repression. Arch Pharm Res 32:1263–1269
doi: 10.1007/s12272-009-1912-8
pubmed: 19784583
Kuhar M, Imran S, Singh N (2007) Curcumin and quercetin combined with cisplatin to induce apoptosis in human laryngeal carcinoma Hep-2 cells through the mitochondrial pathway. J Cancer Mol 3:121–128
Kang N, Zhang JH, Qiu F et al (2010) Induction of G(2)/M phase arrest and apoptosis by oridonin in human laryngeal carcinoma cells. J Nat Prod 73:1058–1063
doi: 10.1021/np9008199
pubmed: 20496901
Li X, Li X, Wang J et al (2012) Oridonin up-regulates expression of P21 and induces autophagy and apoptosis in human prostate cancer cells. Int J Biol Sci 8:901–912
doi: 10.7150/ijbs.4554
pubmed: 22745580
pmcid: 3385012
Zang L, Xu Q, Ye Y et al (2012) Autophagy enhanced phagocytosis of apoptotic cells by oridonin-treated human histocytic lymphoma U937 cells. Arch Biochem Biophys 518:31–41
doi: 10.1016/j.abb.2011.11.019
pubmed: 22155150
Zeng R, Chen Y, Zhao S et al (2012) Autophagy counteracts apoptosis in human multiple myeloma cells exposed to oridonin in vitro via regulating intracellular ROS and SIRT1. Acta Pharmacol Sin 33:91–100
doi: 10.1038/aps.2011.143
pubmed: 22158107
Wang H, Yu Y, Jiang Z et al (2016) Next-generation proteasome inhibitor MLN9708 sensitizes breast cancer cells to doxorubicin-induced apoptosis. Sci Rep 6:26456
doi: 10.1038/srep26456
pubmed: 27217076
pmcid: 4877646
Wang J, Tan X, Yang Q et al (2016) Inhibition of autophagy promotes apoptosis and enhances anticancer efficacy of adriamycin via augmented ROS generation in prostate cancer cells. Int J Biochem Cell Biol 77:80–90
doi: 10.1016/j.biocel.2016.05.020
pubmed: 27247025
Milano V, Piao Y, LaFortune T et al (2009) Dasatinib-induced autophagy is enhanced in combination with temozolomide in glioma. Mol Cancer Ther 8:394–406
doi: 10.1158/1535-7163.MCT-08-0669
pubmed: 19190119
Cheng Y, Zhang Y, Zhang L et al (2012) MK-2206, a novel allosteric inhibitor of Akt, synergizes with gefitinib against malignant glioma via modulating both autophagy and apoptosis. Mol Cancer Ther 11:154–164
doi: 10.1158/1535-7163.MCT-11-0606
pubmed: 22057914
Zeng R, He J, Peng J et al (2012) The time-dependent autophagy protects against apoptosis with possible involvement of Sirt1 protein in multiple myeloma under nutrient depletion. Ann Hematol 91:407–417
doi: 10.1007/s00277-011-1315-z
pubmed: 21915620
Corcelle E, Djerbi N, Mari M et al (2007) Control of the autophagy maturation step by the MAPK ERK and p38: lessons from environmental carcinogens. Autophagy 3:57–59
doi: 10.4161/auto.3424
pubmed: 17102581
Zhang J, Chiu JF, Zhang HW et al (2013) Autophagic cell death induced by resveratrol depends on the Ca(2+)/AMPK/mTOR pathway in A549 cells. Biochem Pharmacol 86:317–328
doi: 10.1016/j.bcp.2013.05.003
pubmed: 23680031
Chen L, Jiang Z, Ma H et al (2016) Volatile oil of Acori Graminei Rhizoma-induced apoptosis and autophagy are dependent on p53 status in human glioma cells. Sci Rep 6:21148
doi: 10.1038/srep21148
pubmed: 26892186
pmcid: 4759692
An HK, Kim KS, Lee JW et al (2016) Mimulone-induced autophagy through p53-mediated AMPK/mTOR pathway increases caspase-mediated apoptotic cell death in A549 human lung cancer cells. PLoS ONE 9:e114607
doi: 10.1371/journal.pone.0114607
Amin AR, Khuri FR, Chen ZG et al (2009) Synergistic growth inhibition of squamous cell carcinoma of the head and neck by erlotinib and epigallocatechin-3-gallate: the role of p53-dependent inhibition of nuclear factor-kappaB. Cancer Prev Res 2:538–545
doi: 10.1158/1940-6207.CAPR-09-0063
Vequaud E, Seveno C, Loussouarn D et al (2015) YM155 potently triggers cell death in breast cancer cells through an autophagy-NF-κB network. Oncotarget 6:13476–13486
doi: 10.18632/oncotarget.3638
pubmed: 25974963
pmcid: 4537028
Li T, Zhang Q, Zhang J et al (2014) Fenofibrate induces apoptosis of triple-negative breast cancer cells via activation of NF-κB pathway. BMC Cancer 14:96
doi: 10.1186/1471-2407-14-96
pubmed: 24529079
pmcid: 4015735
Zhao B, Ma Y, Xu Z et al (2014) Hydroxytyrosol, a natural molecule from olive oil, suppresses the growth of human hepatocellular carcinoma cells via inactivating AKT and nuclear factor-kappa B pathways. Cancer Lett 347:79–87
doi: 10.1016/j.canlet.2014.01.028
pubmed: 24486741
Copetti T, Bertoli C, Dalla E et al (2009) p65/RelA modulates BECN1 transcription and autophagy. Mol Cell Biol 29:2594–25608
doi: 10.1128/MCB.01396-08
pubmed: 19289499
pmcid: 2682036
Park SE, Yi HJ, Suh N et al (2016) Inhibition of EHMT2/G9a epigenetically increases the transcription of Beclin-1 via an increase in ROS and activation of NF-kappaB. Oncotarget 7:39796–39808
pubmed: 27174920
pmcid: 5129971