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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2017

Open Access 01-12-2017 | Research article

Anti-cancer effect of Scutellaria baicalensis in combination with cisplatin in human ovarian cancer cell

Authors: Bo Yoon Choi, Jong Cheon Joo, Yeon Kyu Lee, Ik-Soon Jang, Soo Jung Park, Yoon Jung Park

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

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Abstract

Background

Ovarian cancer is one of the major causes of death among females in worldwide. Cisplatin is a primary anti-cancer drug against ovarian cancer, but the recurrent tumors after treatment frequently show acquired chemoresistance. Extract of Scutellaria baicalensis (SbE) has been reported to have functional compounds including baicalin, which has anti-cancer effects. However, the anti-cancer effects of SbE in ovarian cancer and its underlying mechanisms are elusive.

Methods

We investigated that the effects of SbE and/or cisplatin on cell death in the cisplatin sensitive ovarian cancer cell line A2780 (CSC) and the counterpart cell line that has cisplatin resistance (CRC). Molecular mechanisms of the effects, focusing on apoptosis and autophagy, were examined.

Results

Treatment of cisplatin or SbE reduced cell viability significantly in CSC and too much lesser extent in CRC. Cisplatin-induced cell death in CSC was mediated by p53-induced apoptosis acompanied by expresson of damage-regulated autophagy modulator (DRAM). In CRC, decreased DRAM expression (p < 0.01) hindered p21-mediated cell death and contributed to cisplatin resistance. Treatment of SbE also induced cell death in CSC by p53-dependent apoptosis, not in CRC. Autophagy was not induced by neither cisplatin nor SbE. Intriguingly, the combinational treatment of SbE and cisplatin significantly decreased cell viability in CRC. The cell death was mediated by autophagy with increased expression of Atg5 and Atg12 (p < 0.05), rather than p53-dependent pathway with repressed expression of p21 (p < 0.001) through HDAC1 activation.

Conclusions

The combined treatment of SbE with cisplatin was effective in CRC, leading to cell death via Beclin1-independent autophagy, suggesting that SbE treatment in combination with cisplatin has a potential as a chemotherapeutic agent in cisplatin-resistant ovarian cancer.
Literature
1.
2.
McGuire WP, et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med. 1996;334(1):1–6.CrossRefPubMed
3.
Howlader N, Noone A, Krapcho M. SEER Cancer Statistics Review, 1975–2013. Bethesda: National Cancer Institute; 2016.
4.
Markman M, et al. Responses to second-line cisplatin-based intraperitoneal therapy in ovarian cancer: influence of a prior response to intravenous cisplatin. J Clin Oncol. 1991;9(10):1801–5.CrossRefPubMed
5.
Ohmichi M, et al. Mechanisms of platinum drug resistance. Trends Pharmacol Sci. 2005;26(3):113–6.CrossRefPubMed
6.
Xu X, et al. Genetic polymorphism of copper transporter protein 1 is related to platinum resistance in Chinese non-small cell lung carcinoma patients. Clin Exp Pharmacol Physiol. 2012;39(9):786–92.CrossRefPubMed
7.
8.
Dabholkar M, et al. ERCC1 and ERCC2 expression in malignant tissues from ovarian cancer patients. J Natl Cancer Inst. 1992;84(19):1512–7.CrossRefPubMed
9.
Sui L, et al. Survivin expression and its correlation with cell proliferation and prognosis in epithelial ovarian tumors. Int J Oncol. 2002;21(2):315–20.PubMed
10.
Perego P, et al. Association between cisplatin resistance and mutation of p53 gene and reduced bax expression in ovarian carcinoma cell systems. Cancer Res. 1996;56(3):556–62.PubMed
11.
Green DR. Means to an end: apoptosis and other cell death mechanisms. Cold Spring Harbor: Cold Spring Harbor Laboratory Press; 2011.
12.
Lowe SW, et al. p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell. 1993;74(6):957–67.CrossRefPubMed
13.
14.
El-Deiry WS, et al. WAF1, a potential mediator of p53 tumor suppression. Cell. 1993;75(4):817–25.CrossRefPubMed
15.
Ahmad N, et al. Resveratrol causes WAF-1/p 21-mediated G1-phase arrest of cell cycle and induction of apoptosis in human epidermoid carcinoma A431 cells. Clin Cancer Res. 2001;7(5):1466–73.PubMed
16.
Crighton D, et al. DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. Cell. 2006;126(1):121–34.CrossRefPubMed
17.
Kondo Y, et al. The role of autophagy in cancer development and response to therapy. Nat Rev Cancer. 2005;5(9):726–34.CrossRefPubMed
18.
Kaur J, Debnath J. Autophagy at the crossroads of catabolism and anabolism. Nat Rev Mol Cell Biol. 2015;16(8):461–72.CrossRefPubMed
19.
20.
Huang W-H, Lee A-R, Yang C-H. Antioxidative and anti-inflammatory activities of polyhydroxyflavonoids of Scutellaria Baicalensis GEORGI. Biosci Biotechnol Biochem. 2006;70(10):2371–80.CrossRefPubMed
21.
Zhou Q-M, et al. The combination of baicalin and baicalein enhances apoptosis via the ERK/p38 MAPK pathway in human breast cancer cells. Acta Pharmacol Sin. 2009;30(12):1648–58.CrossRefPubMedPubMedCentral
22.
Ikezoe T, et al. Baicalin is a major component of PC-SPES which inhibits the proliferation of human cancer cells via apoptosis and cell cycle arrest. Prostate. 2001;49(4):285–92.CrossRefPubMed
23.
Kumagai T, et al. Scutellaria Baicalensis, a herbal medicine: anti-proliferative and apoptotic activity against acute lymphocytic leukemia, lymphoma and myeloma cell lines. Leuk Res. 2007;31(4):523–30.CrossRefPubMed
24.
Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1–2):55–63.CrossRefPubMed
25.
Culmsee C, Mattson MP. p53 in neuronal apoptosis. Biochem Biophys Res Commun. 2005;331(3):761–77.CrossRefPubMed
26.
Harris CC. Structure and function of the p53 tumor suppressor gene: clues for rational cancer therapeutic strategies. J Natl Cancer Inst. 1996;88(20):1442–55.CrossRefPubMed
27.
Mizushima N, et al. A protein conjugation system essential for autophagy. Nature. 1998;395(6700):395–8.CrossRefPubMed
28.
Ye F, et al. Quality evaluation of commercial extracts of Scutellaria Baicalensis. Nutr Cancer. 2004;49(2):217–22.CrossRefPubMed
29.
Xu X-F, et al. Baicalin induces human mucoepidermoid carcinoma Mc3 cells apoptosis in vitro and in vivo. Investig New Drugs. 2011;29(4):637–45.CrossRef
30.
Egger G, et al. Epigenetics in human disease and prospects for epigenetic therapy. Nature. 2004;429(6990):457–63.CrossRefPubMed
31.
32.
33.
Lagger G, et al. The tumor suppressor p53 and histone deacetylase 1 are antagonistic regulators of the cyclin-dependent kinase inhibitor p21/WAF1/CIP1 gene. Mol Cell Biol. 2003;23(8):2669–79.CrossRefPubMedPubMedCentral
34.
Scarlatti F, et al. Role of non-canonical Beclin 1-independent autophagy in cell death induced by resveratrol in human breast cancer cells. Cell Death & Differentiation. 2008;15(8):1318–29.CrossRef
35.
Smith D, et al. Arsenic trioxide induces a beclin-1-independent autophagic pathway via modulation of SnoN/SkiL expression in ovarian carcinoma cells. Cell Death & Differentiation. 2010;17(12):1867–81.CrossRef
36.
Wu J, et al. Molecular cloning and characterization of rat LC3A and LC3B—two novel markers of autophagosome. Biochem Biophys Res Commun. 2006;339(1):437–42.CrossRefPubMed
Metadata
Title
Anti-cancer effect of Scutellaria baicalensis in combination with cisplatin in human ovarian cancer cell
Authors
Bo Yoon Choi
Jong Cheon Joo
Yeon Kyu Lee
Ik-Soon Jang
Soo Jung Park
Yoon Jung Park
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-017-1776-2

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