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Indian Journal of Hematology and Blood Transfusion
Published in: Indian Journal of Hematology and Blood Transfusion 2/2018

01-04-2018 | Original Article

Bufalin Enhances the Cytotoxity of Human Multiple Myeloma Cells H929 to AKT Inhibitor MK2206: The Role of Protein AKT Phosphorylation

Authors: He Huang, Xiao-ji Lin, Ying Lin, Ron-xin Yao, Mu-qing He

Published in: Indian Journal of Hematology and Blood Transfusion | Issue 2/2018

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Abstract

This study was purposed to investigate bufalin combined with AKT inhibitor MK2206 on growth inhibition and apoptosis of multiple myeloma cell line H929. CCK-8 assay and Annexin/PI staining were used to access the effects of bufalin and MK2206 in single or in combination, on inhibition of proliferation and induction of apoptosis in H929 cells. The apoptotic cells markedly increased after treated with nM bufalin and μM MK2206, including caspase3 and PARP1 proteins activated. The difference was statistically significant (P < 0.05) when compared with these drugs in single use. The apoptosis associated proteins and AKT/p-AKT proteins were determined by Western blots. We confirmed that AKT performed contradictory results in H929 with the two agents, and concluded p-AKT was vital in the synergy. The underlying mechanisms warrant further investigation.
Literature
1.
Kumar S, Paiva B, Anderson KC et al (2016) International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 17(8):e328–e346CrossRefPubMed
2.
Hsu J, Shi Y, Krajewski S et al (2001) The AKT kinase is activated in multiple myeloma tumor cells. Blood 98(9):2853–2855CrossRefPubMed
3.
Keane NA, Glavey SV, Krawczyk J et al (2014) AKT as a therapeutic target in multiple myeloma. Expert Opin Ther Targets 18(8):897–915CrossRefPubMed
4.
Toker A, Yoeli-Lerner M (2006) Akt signaling and cancer: surviving but not moving on. Cancer Res 66(8):3963–3966CrossRefPubMed
5.
Song G, Ouyang G, Bao S (2005) The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med 9(1):59–71CrossRefPubMed
6.
Hirai H, Sootome H, Nakatsuru Y et al (2010) MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Mol Cancer Ther 9(7):1956–1967CrossRefPubMed
7.
Ramakrishnan V, Kimlinger T, Haug J et al (2012) Anti-myeloma activity of Akt inhibition is linked to the activation status of PI3K/Akt and MEK/ERK pathway. PLoS ONE 7(11):e50005CrossRefPubMedPubMedCentral
8.
Huang H, Cao Y, Wei W et al (2013) Targeting poly (ADP-ribose) polymerase partially contributes to bufalin-induced cell death in multiple myeloma cells. PLoS ONE 8(6):e66130CrossRefPubMedPubMedCentral
9.
Zhang LS, Nakaya K, Yoshida T et al (1991) Bufalin as a potent inducer of differentiation of human myeloid leukemia cells. Biochem Biophys Res Commun 178(2):686–693CrossRefPubMed
10.
Zhang L, Nakaya K, Yoshida T et al (1992) Induction by bufalin of differentiation of human leukemia cells HL60, U937, and ML1 toward macrophage/monocyte-like cells and its potent synergistic effect on the differentiation of human leukemia cells in combination with other inducers. Cancer Res 52(17):4634–4641PubMed
11.
Chen A, Yu J, Zhang L, Sun Y et al (2009) Microarray and biochemical analysis of bufalin-induced apoptosis of HL-60 Cells. Biotechnol Lett 31(4):487–494CrossRefPubMed
12.
Yeh JY, Huang WJ, Kan SF et al (2003) Effects of bufalin and cinobufagin on the proliferation of androgen dependent and independent prostate cancer cells. Prostate 54(2):112–124CrossRefPubMed
13.
Takai N, Ueda T, Nishida M et al (2008) Bufalin induces growth inhibition, cell cycle arrest and apoptosis in human endometrial and ovarian cancer cells. Int J Mol Med 21(5):637–643PubMed
14.
Li D, Qu X, Hou K et al (2009) PI3K/Akt is involved in bufalin-induced apoptosis in gastric cancer cells. Anticancer Drugs 20(20):59–64CrossRefPubMed
15.
Meng Z, Yang P, Shen Y et al (2009) Pilot study of huachansu in patients with hepatocellular carcinoma, nonsmall-cell lung cancer, or pancreatic cancer. Cancer 115(22):5309–5318CrossRefPubMedPubMedCentral
16.
Qi F, Li A, Zhao L et al (2010) Cinobufacini, an aqueous extract from Bufo bufo gargarizans Cantor, induces apoptosis through a mitochondria-mediated pathway in human hepatocellular carcinoma cells. J Ethnopharmacol 128(3):654–661CrossRefPubMed
17.
Takai N, Kira N, Ishii T et al (2012) Bufalin, a traditional oriental medicine, induces apoptosis in human cancer cells. Asian Pac J Cancer Prev 13(1):399–402CrossRefPubMed
18.
Arnaud-Batista FJ, Costa GT, Oliveira IM et al (2012) Natriuretic effect of bufalin in isolated rat kidneys involves activation of the Na+-K+-ATPase-Src kinase pathway. Am J Physiol Renal Physiol 302(8):F959–F966CrossRefPubMed
19.
Zhao Y, Pu JX, Huang SX et al (2009) ent-Kaurane diterpenoids from Isodon pharicus. J Nat Prod 72(6):988–993CrossRefPubMed
20.
Yin PH, Liu X, Qiu YY et al (2012) Anti-tumor activity and apoptosis-regulation mechanisms of bufalin in various cancers: new hope for cancer patients. Asian Pac J Cancer Prev 13(11):5339–5343CrossRefPubMed
21.
22.
Demel HR, Feuerecker B, Piontek G et al (2015) Effects of topoisomerase inhibitors that induce DNA damage response on glucose metabolism and PI3K/Akt/mTOR signaling in multiple myeloma cells. Am J Cancer Res 5(5):1649–1664PubMedPubMedCentral
Metadata
Title
Bufalin Enhances the Cytotoxity of Human Multiple Myeloma Cells H929 to AKT Inhibitor MK2206: The Role of Protein AKT Phosphorylation
Authors
He Huang
Xiao-ji Lin
Ying Lin
Ron-xin Yao
Mu-qing He
Publication date
01-04-2018
Publisher
Springer India
Published in
Indian Journal of Hematology and Blood Transfusion / Issue 2/2018
Print ISSN: 0971-4502
Electronic ISSN: 0974-0449
DOI
https://doi.org/10.1007/s12288-017-0883-z

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