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Published in: BMC Complementary Medicine and Therapies 1/2013

Open Access 01-12-2013 | Research article

MiR-181a contributes to bufalin-induced apoptosis in PC-3 prostate cancer cells

Authors: Xiao-feng Zhai, Fan-fu Fang, Qun Liu, Yong-bin Meng, Yu-yu Guo, Zhe Chen

Published in: BMC Complementary Medicine and Therapies | Issue 1/2013

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Abstract

Background

Bufalin is a major active compound of cinobufacini, which comes from dried toad venom and has been used for treatments of various cancers in China for many years. A number of studies have demonstrated that bufalin can induce apoptosis in some cancers. However, effects and mechanism of bufalin on prostate cancer cells remain unknown.

Methods

Apoptosis assay was measured by the annexin-V/PI flow cytometric assay. Western blot was used to measure Caspase-3 and Bcl-2. qRT-PCR was used to measure the relative expression of miR-181a.

Results

Bufalin was found to induce the expression of miR-181a, a small non-coding RNA believed to induce apoptosis by repressing its target gene, BCL-2. In prostate cancer PC-3cell line, bufalin-induced apoptosis can be largely attenuated by a miR-181a inhibitor, which blocked bufalin-induced Bcl-2 reduction and caspase-3 activation.

Conclusions

Our dataindicatedthat miR-181a mediates bufalin-induced apoptosis in PC-3 cells. Thus, we presented here a new pharmacological mechanism for bufalin in anti-tumor therapy.
Appendix
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Literature
1.
go back to reference Yang LH, Jin XQ, Zhang WD: Studies on the chemical constituents from the skin of Bufo bufo gargarizans cantor. Journal of Shenyang Pharmaceutical University. 2000, 17: 292-295. Yang LH, Jin XQ, Zhang WD: Studies on the chemical constituents from the skin of Bufo bufo gargarizans cantor. Journal of Shenyang Pharmaceutical University. 2000, 17: 292-295.
2.
go back to reference Qi FH, Li AY, Inagaki Y, Kokudo N, Tamura S, Nakata M, Tang W: Antitumor activity of extracts and compounds from the skin of the toad Bufo bufo gargarizans Cantor. Int Immunopharmacol. 2010, 11: 342-349.CrossRefPubMed Qi FH, Li AY, Inagaki Y, Kokudo N, Tamura S, Nakata M, Tang W: Antitumor activity of extracts and compounds from the skin of the toad Bufo bufo gargarizans Cantor. Int Immunopharmacol. 2010, 11: 342-349.CrossRefPubMed
3.
go back to reference Li D, Qu X, Hou K, Zhang Y, Dong Q, Teng Y, Zhang J, Liu Y: PI3K/Akt is involved in bufalin-induced apoptosis in gastric cancer cells. Anticancer Drugs. 2009, 20: 59-64. 10.1097/CAD.0b013e3283160fd6.CrossRefPubMed Li D, Qu X, Hou K, Zhang Y, Dong Q, Teng Y, Zhang J, Liu Y: PI3K/Akt is involved in bufalin-induced apoptosis in gastric cancer cells. Anticancer Drugs. 2009, 20: 59-64. 10.1097/CAD.0b013e3283160fd6.CrossRefPubMed
4.
go back to reference Yu CH, Kan SF, Pu HF, Jea Chien E, Wang PS: Apoptotic signaling in bufalin- and cinobufagin-treated androgen-dependent and -independent human prostate cancer cells. Cancer Sci. 2008, 99: 2467-2476. 10.1111/j.1349-7006.2008.00966.x.CrossRefPubMed Yu CH, Kan SF, Pu HF, Jea Chien E, Wang PS: Apoptotic signaling in bufalin- and cinobufagin-treated androgen-dependent and -independent human prostate cancer cells. Cancer Sci. 2008, 99: 2467-2476. 10.1111/j.1349-7006.2008.00966.x.CrossRefPubMed
5.
go back to reference Sun L, Chen T, Wang X, Chen Y, Wei X: Bufalin induces reactive oxygen species dependent bax translocation and apoptosis in ASTC-a-1 Cells. Evid Based Complement Alternat Med. 2011, 2011: 249090-CrossRefPubMedPubMedCentral Sun L, Chen T, Wang X, Chen Y, Wei X: Bufalin induces reactive oxygen species dependent bax translocation and apoptosis in ASTC-a-1 Cells. Evid Based Complement Alternat Med. 2011, 2011: 249090-CrossRefPubMedPubMedCentral
6.
go back to reference Han KQ, Huang G, Gu W, Su YH, Huang XQ, Ling CQ: Anti-tumor activities and apoptosis-regulated mechanisms of bufalin on the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice. World J Gastroenterol. 2007, 13: 3374-3379.CrossRefPubMedPubMedCentral Han KQ, Huang G, Gu W, Su YH, Huang XQ, Ling CQ: Anti-tumor activities and apoptosis-regulated mechanisms of bufalin on the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice. World J Gastroenterol. 2007, 13: 3374-3379.CrossRefPubMedPubMedCentral
7.
go back to reference Takai N, Ueda T, Nishida M, Nasu K, Narahara H: Bufalin induces growth inhibition, cell cycle arrest and apoptosis in human endometrial and ovarian cancer cells. Int J Mol Med. 2008, 21: 637-643.PubMed Takai N, Ueda T, Nishida M, Nasu K, Narahara H: Bufalin induces growth inhibition, cell cycle arrest and apoptosis in human endometrial and ovarian cancer cells. Int J Mol Med. 2008, 21: 637-643.PubMed
9.
go back to reference Garzon R, Calin GA, Croce CM: MicroRNAs in Cancer. Annu Rev Med. 2009, 60: 167-179. 10.1146/annurev.med.59.053006.104707.CrossRefPubMed Garzon R, Calin GA, Croce CM: MicroRNAs in Cancer. Annu Rev Med. 2009, 60: 167-179. 10.1146/annurev.med.59.053006.104707.CrossRefPubMed
11.
go back to reference Ruan K, Fang XG, Ouyang GL: MicroRNAs: novel regulators in the hallmarks of human cancer. Cancer Lett. 2009, 285: 116-126. 10.1016/j.canlet.2009.04.031.CrossRefPubMed Ruan K, Fang XG, Ouyang GL: MicroRNAs: novel regulators in the hallmarks of human cancer. Cancer Lett. 2009, 285: 116-126. 10.1016/j.canlet.2009.04.031.CrossRefPubMed
12.
go back to reference Chen CZ, Li L, Lodish HF, Bartel DP: MicroRNAs modulate hematopoietic lineage differentiation. Science. 2004, 303: 83-86. 10.1126/science.1091903.CrossRefPubMed Chen CZ, Li L, Lodish HF, Bartel DP: MicroRNAs modulate hematopoietic lineage differentiation. Science. 2004, 303: 83-86. 10.1126/science.1091903.CrossRefPubMed
13.
go back to reference Shi L, Cheng ZH, Zhang JX, Li R, Zhao P, Fu Z, You YP: hsa-mir-181a and hsa-mir-181b function as tumor suppressors in human glioma cells. Brain Res. 2008, 1236: 185-193.CrossRefPubMed Shi L, Cheng ZH, Zhang JX, Li R, Zhao P, Fu Z, You YP: hsa-mir-181a and hsa-mir-181b function as tumor suppressors in human glioma cells. Brain Res. 2008, 1236: 185-193.CrossRefPubMed
14.
go back to reference Ouyang YB, Lu Y, Yue S, Giffard RG: miR-181 targets multiple Bcl-2 family members and influences apoptosis and mitochondrial function in astrocytes. Mitochondrion. 2011, 12: 213-219.CrossRefPubMedPubMedCentral Ouyang YB, Lu Y, Yue S, Giffard RG: miR-181 targets multiple Bcl-2 family members and influences apoptosis and mitochondrial function in astrocytes. Mitochondrion. 2011, 12: 213-219.CrossRefPubMedPubMedCentral
15.
go back to reference Bai H, Cao Z, Deng C, Zhou L, Wang C: miR-181a sensitizes resistant leukaemia HL-60/Ara-C cells to Ara-C by inducing apoptosis. J Cancer Res Clin Oncol. 2012, 138: 595-602. 10.1007/s00432-011-1137-3.CrossRefPubMed Bai H, Cao Z, Deng C, Zhou L, Wang C: miR-181a sensitizes resistant leukaemia HL-60/Ara-C cells to Ara-C by inducing apoptosis. J Cancer Res Clin Oncol. 2012, 138: 595-602. 10.1007/s00432-011-1137-3.CrossRefPubMed
16.
go back to reference Chen G, Zhu W, Shi DZ, Lv L, Zhang C, Liu P, Hu WX: MicroRNA-181a sensitizes human malignant glioma U87MG cells to radiation by targeting Bcl-2. Oncol Rep. 2010, 23: 997-1003.PubMed Chen G, Zhu W, Shi DZ, Lv L, Zhang C, Liu P, Hu WX: MicroRNA-181a sensitizes human malignant glioma U87MG cells to radiation by targeting Bcl-2. Oncol Rep. 2010, 23: 997-1003.PubMed
17.
go back to reference Galluzzi L, Morselli E, Vitale I, Kepp O, Senovilla L, Criollo A, Servant N, Paccard C, Hupe P, Robert T: miR-181a and miR-630 regulate cisplatin-induced cancer cell death. Cancer Res. 2010, 70: 1793-1803. 10.1158/0008-5472.CAN-09-3112.CrossRefPubMed Galluzzi L, Morselli E, Vitale I, Kepp O, Senovilla L, Criollo A, Servant N, Paccard C, Hupe P, Robert T: miR-181a and miR-630 regulate cisplatin-induced cancer cell death. Cancer Res. 2010, 70: 1793-1803. 10.1158/0008-5472.CAN-09-3112.CrossRefPubMed
18.
go back to reference Li H, Hui LL, Xu WL: miR-181a sensitizes a multidrug-resistant leukemia cell line K562/A02 to daunorubicin by targeting BCL-2. Acta Biochim Biophys Sin (Shanghai). 2012, 44: 269-277. 10.1093/abbs/gmr128.CrossRef Li H, Hui LL, Xu WL: miR-181a sensitizes a multidrug-resistant leukemia cell line K562/A02 to daunorubicin by targeting BCL-2. Acta Biochim Biophys Sin (Shanghai). 2012, 44: 269-277. 10.1093/abbs/gmr128.CrossRef
19.
go back to reference Zhu DX, Zhu W, Fang C, Fan L, Zou ZJ, Wang YH, Liu P, Hong M, Miao KR, Xu W, Li JY: miR-181a/b significantly enhances drug sensitivity in chronic lymphocytic leukemia cells via targeting multiple anti-apoptosis genes. Carcinogenesis. 2012, 33: 1294-1301. 10.1093/carcin/bgs179.CrossRefPubMed Zhu DX, Zhu W, Fang C, Fan L, Zou ZJ, Wang YH, Liu P, Hong M, Miao KR, Xu W, Li JY: miR-181a/b significantly enhances drug sensitivity in chronic lymphocytic leukemia cells via targeting multiple anti-apoptosis genes. Carcinogenesis. 2012, 33: 1294-1301. 10.1093/carcin/bgs179.CrossRefPubMed
20.
go back to reference Zhu W, Shan X, Wang TS, Shu YQ, Liu P: miR-181b modulates multidrug resistance by targeting BCL2 in human cancer cell lines. Int J Cancer. 2010, 127: 2520-2529. 10.1002/ijc.25260.CrossRefPubMed Zhu W, Shan X, Wang TS, Shu YQ, Liu P: miR-181b modulates multidrug resistance by targeting BCL2 in human cancer cell lines. Int J Cancer. 2010, 127: 2520-2529. 10.1002/ijc.25260.CrossRefPubMed
21.
go back to reference Fei J, Li Y, Zhu X, Luo X: miR-181a post-transcriptionally downregulates oncogenic RalA and contributes to growth inhibition and apoptosis in chronic myelogenous leukemia (CML). PLoS One. 2012, 7: e32834-10.1371/journal.pone.0032834.CrossRefPubMedPubMedCentral Fei J, Li Y, Zhu X, Luo X: miR-181a post-transcriptionally downregulates oncogenic RalA and contributes to growth inhibition and apoptosis in chronic myelogenous leukemia (CML). PLoS One. 2012, 7: e32834-10.1371/journal.pone.0032834.CrossRefPubMedPubMedCentral
22.
go back to reference Cho WC: MicroRNAs in cancer - from research to therapy. Biochim Biophys Acta. 1805, 2009: 209-217. Cho WC: MicroRNAs in cancer - from research to therapy. Biochim Biophys Acta. 1805, 2009: 209-217.
23.
go back to reference Masuda Y, Kawazoe N, Nakajo S, Yoshida T, Kuroiwa Y, Nakaya K: Bufalin induces apoptosis and influences the expression of apoptosis-related genes in human leukemia cells. Leuk Res. 1995, 19: 549-556. 10.1016/0145-2126(95)00031-I.CrossRefPubMed Masuda Y, Kawazoe N, Nakajo S, Yoshida T, Kuroiwa Y, Nakaya K: Bufalin induces apoptosis and influences the expression of apoptosis-related genes in human leukemia cells. Leuk Res. 1995, 19: 549-556. 10.1016/0145-2126(95)00031-I.CrossRefPubMed
24.
go back to reference Watabe M, Masuda Y, Nakajo S, Yoshida T, Kuroiwa Y, Nakaya K: The cooperative interaction of two different signaling pathways in response to bufalin induces apoptosis in human leukemia U937 cells. J Biol Chem. 1996, 271: 14067-14072. 10.1074/jbc.271.24.14067.CrossRefPubMed Watabe M, Masuda Y, Nakajo S, Yoshida T, Kuroiwa Y, Nakaya K: The cooperative interaction of two different signaling pathways in response to bufalin induces apoptosis in human leukemia U937 cells. J Biol Chem. 1996, 271: 14067-14072. 10.1074/jbc.271.24.14067.CrossRefPubMed
25.
go back to reference Watabe M, Ito K, Masuda Y, Nakajo S, Nakaya K: Activation of AP-1 is required for bufalin-induced apoptosis in human leukemia U937 cells. Oncogene. 1998, 16: 779-787. 10.1038/sj.onc.1201592.CrossRefPubMed Watabe M, Ito K, Masuda Y, Nakajo S, Nakaya K: Activation of AP-1 is required for bufalin-induced apoptosis in human leukemia U937 cells. Oncogene. 1998, 16: 779-787. 10.1038/sj.onc.1201592.CrossRefPubMed
26.
go back to reference Watabe M, Kawazoe N, Masuda Y, Nakajo S, Nakaya K: Bcl-2 protein inhibits bufalin-induced apoptosis through inhibition of mitogen-activated protein kinase activation in human leukemia U937 cells. Cancer Res. 1997, 57: 3097-3100.PubMed Watabe M, Kawazoe N, Masuda Y, Nakajo S, Nakaya K: Bcl-2 protein inhibits bufalin-induced apoptosis through inhibition of mitogen-activated protein kinase activation in human leukemia U937 cells. Cancer Res. 1997, 57: 3097-3100.PubMed
27.
go back to reference Zhai XF, Chen Z, Li B, Shen F, Fan J, Zhou WP, Yang YK, Xu J, Qin X, Li LQ, Ling CQ: Traditional herbal medicine in preventing recurrence after resection of small hepatocellular carcinoma: a multicenter randomized controlled trial. J Integr Med. 2013, 2: 90-100.CrossRef Zhai XF, Chen Z, Li B, Shen F, Fan J, Zhou WP, Yang YK, Xu J, Qin X, Li LQ, Ling CQ: Traditional herbal medicine in preventing recurrence after resection of small hepatocellular carcinoma: a multicenter randomized controlled trial. J Integr Med. 2013, 2: 90-100.CrossRef
Metadata
Title
MiR-181a contributes to bufalin-induced apoptosis in PC-3 prostate cancer cells
Authors
Xiao-feng Zhai
Fan-fu Fang
Qun Liu
Yong-bin Meng
Yu-yu Guo
Zhe Chen
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2013
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/1472-6882-13-325

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