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Published in: Investigational New Drugs 4/2011

01-08-2011 | PRECLINICAL STUDIES

Baicalin induces human mucoepidermoid carcinoma Mc3 cells apoptosis in vitro and in vivo

Authors: Xiao-Fang Xu, Bo-Lei Cai, Su-Min Guan, Yan Li, Jun-Zheng Wu, Yong Wang, Bin Liu

Published in: Investigational New Drugs | Issue 4/2011

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Summary

Mucoepidermoid carcinoma (MEC) is the most common malignant tumor in salivary glands and high-grade MEC in particular demonstrates little response to chemotherapy which has been used largely for palliative treatment of metastatic disease. Baicalin, one of the main active compounds of Scutellaria baicalensis, possesses anti-inflammatory, antioxidant and antitumor properties. In the present study, we investigated the growth inhibiting and apoptosis-inducing effects of baicalin on a highly metastatic human mucoepidermoid carcinoma cell line Mc3 for the first time. Baicalin exerted dose- and time-dependent antiproliferative potential against Mc3 cells as assessed by MTT assay. Baicalin treatment of Mc3 cells resulted in an accumulation of cells at the G0/G1 and G2/M phase with a concomitant decrease in cells processing to S phase as assessed by flow cytometry. Furthermore, baicalin induced apoptosis of Mc3 cells as determined by annexin V binding and PI dual staining, DNA fragmentation, nuclear condensation and in vivo tumor inhabitation. Rhodamine 123 assay indicated that baicalin caused cytotoxicity and induced apoptosis through decreasing the mitochondrial membrane potential in Mc3 cells. Our results suggest that baicalin seems to be very attractive as a new anticancer drug and a potential chemotherapeutic agent against human high-grade mucoepidermoid carcinoma.
Literature
1.
go back to reference Eveson JW, Cawson RA (1985) Salivary gland tumours. A review of 2410 cases with particular reference to histological types, site, age and sex distribution. J Pathol 146:51–58PubMedCrossRef Eveson JW, Cawson RA (1985) Salivary gland tumours. A review of 2410 cases with particular reference to histological types, site, age and sex distribution. J Pathol 146:51–58PubMedCrossRef
2.
go back to reference Aro K, Leivo I, Makitie AA (2008) Management and outcome of patients with mucoepidermoid carcinoma of major salivary gland origin: a single institution's 30-year experience. Laryngoscope 118:258–262PubMedCrossRef Aro K, Leivo I, Makitie AA (2008) Management and outcome of patients with mucoepidermoid carcinoma of major salivary gland origin: a single institution's 30-year experience. Laryngoscope 118:258–262PubMedCrossRef
4.
go back to reference Vattemi E, Graiff C, Sava T, Pedersini R, Caldara A, Mandara M (2008) Systemic therapies for recurrent and/or metastatic salivary gland cancers. Expert Rev Anticancer Ther 8:393–402PubMedCrossRef Vattemi E, Graiff C, Sava T, Pedersini R, Caldara A, Mandara M (2008) Systemic therapies for recurrent and/or metastatic salivary gland cancers. Expert Rev Anticancer Ther 8:393–402PubMedCrossRef
5.
go back to reference Ruan WJ, Lai MD, Zhou JG (2006) Anticancer effects of Chinese herbal medicine, science or myth? J Zhejiang Univ Sci B 7:1006–1014PubMedCrossRef Ruan WJ, Lai MD, Zhou JG (2006) Anticancer effects of Chinese herbal medicine, science or myth? J Zhejiang Univ Sci B 7:1006–1014PubMedCrossRef
6.
go back to reference Zhang M, Liu X, Li J, He L, Tripathy D (2007) Chinese medicinal herbs to treat the side-effects of chemotherapy in breast cancer patients. Cochrane Database Syst Rev:CD004921 Zhang M, Liu X, Li J, He L, Tripathy D (2007) Chinese medicinal herbs to treat the side-effects of chemotherapy in breast cancer patients. Cochrane Database Syst Rev:CD004921
7.
go back to reference Baylor NW, Fu T, Yan YD, Ruscetti FW (1992) Inhibition of human T cell leukemia virus by the plant flavonoid baicalin (7-glucuronic acid, 5, 6-dihydroxyflavone). J Infect Dis 165:433–437PubMedCrossRef Baylor NW, Fu T, Yan YD, Ruscetti FW (1992) Inhibition of human T cell leukemia virus by the plant flavonoid baicalin (7-glucuronic acid, 5, 6-dihydroxyflavone). J Infect Dis 165:433–437PubMedCrossRef
8.
go back to reference Chenn S (2001) In vitro mechanism of PC SPES. Urology 58(28–35):38 Chenn S (2001) In vitro mechanism of PC SPES. Urology 58(28–35):38
9.
go back to reference Ikemoto S, Sugimura K, Yoshida N, Yasumoto R, Wada S, Yamamoto K, Kishimoto T (2000) Antitumor effects of Scutellariae radix and its components baicalein, baicalin, and wogonin on bladder cancer cell lines. Urology 55:951–955PubMedCrossRef Ikemoto S, Sugimura K, Yoshida N, Yasumoto R, Wada S, Yamamoto K, Kishimoto T (2000) Antitumor effects of Scutellariae radix and its components baicalein, baicalin, and wogonin on bladder cancer cell lines. Urology 55:951–955PubMedCrossRef
10.
go back to reference Kitamura K, Honda M, Yoshizaki H, Yamamoto S, Nakane H, Fukushima M, Ono K, Tokunaga T (1998) Baicalin, an inhibitor of HIV-1 production in vitro. Antiviral Res 37:131–140PubMedCrossRef Kitamura K, Honda M, Yoshizaki H, Yamamoto S, Nakane H, Fukushima M, Ono K, Tokunaga T (1998) Baicalin, an inhibitor of HIV-1 production in vitro. Antiviral Res 37:131–140PubMedCrossRef
11.
go back to reference Chen YC, Chow JM, Lin CW, Wu CY, Shen SC (2006) Baicalein inhibition of oxidative-stress-induced apoptosis via modulation of ERKs activation and induction of HO-1 gene expression in rat glioma cells C6. Toxicol Appl Pharmacol 216:263–273PubMedCrossRef Chen YC, Chow JM, Lin CW, Wu CY, Shen SC (2006) Baicalein inhibition of oxidative-stress-induced apoptosis via modulation of ERKs activation and induction of HO-1 gene expression in rat glioma cells C6. Toxicol Appl Pharmacol 216:263–273PubMedCrossRef
12.
go back to reference Woo KJ, Lim JH, Suh SI, Kwon YK, Shin SW, Kim SC, Choi YH, Park JW, Kwon TK (2006) Differential inhibitory effects of baicalein and baicalin on LPS-induced cyclooxygenase-2 expression through inhibition of C/EBPbeta DNA-binding activity. Immunobiology 211:359–368PubMedCrossRef Woo KJ, Lim JH, Suh SI, Kwon YK, Shin SW, Kim SC, Choi YH, Park JW, Kwon TK (2006) Differential inhibitory effects of baicalein and baicalin on LPS-induced cyclooxygenase-2 expression through inhibition of C/EBPbeta DNA-binding activity. Immunobiology 211:359–368PubMedCrossRef
13.
go back to reference Tu XK, Yang WZ, Shi SS, Wang CH, Chen CM (2009) Neuroprotective effect of baicalin in a rat model of permanent focal cerebral ischemia. Neurochem Res 34:1626–1634PubMedCrossRef Tu XK, Yang WZ, Shi SS, Wang CH, Chen CM (2009) Neuroprotective effect of baicalin in a rat model of permanent focal cerebral ischemia. Neurochem Res 34:1626–1634PubMedCrossRef
14.
go back to reference Du G, Han G, Zhang S, Lin H, Wu X, Wang M, Ji L, Lu L, Yu L, Liang W (2009) Baicalin suppresses lung carcinoma and lung metastasis by SOD mimic and HIF-1alpha inhibition. Eur J Pharmacol (Epub ahead of print. doi:10.1016/j.ejphar.2009.12.014) Du G, Han G, Zhang S, Lin H, Wu X, Wang M, Ji L, Lu L, Yu L, Liang W (2009) Baicalin suppresses lung carcinoma and lung metastasis by SOD mimic and HIF-1alpha inhibition. Eur J Pharmacol (Epub ahead of print. doi:10.​1016/​j.​ejphar.​2009.​12.​014)
15.
go back to reference Wen DS, Zhu XL, Guan SM, Wu YM, Yu LL, Wu JZ (2008) Silencing of CXCR4 inhibits the proliferation, adhesion, chemotaxis and invasion of salivary gland mucoepidermoid carcinoma Mc3 cells in vitro. Oral Oncol 44:545–554PubMedCrossRef Wen DS, Zhu XL, Guan SM, Wu YM, Yu LL, Wu JZ (2008) Silencing of CXCR4 inhibits the proliferation, adhesion, chemotaxis and invasion of salivary gland mucoepidermoid carcinoma Mc3 cells in vitro. Oral Oncol 44:545–554PubMedCrossRef
16.
go back to reference Singh M, Tyagi S, Bhui K, Prasad S, Shukla Y (2009) Regulation of cell growth through cell cycle arrest and apoptosis in HPV 16 positive human cervical cancer cells by tea polyphenols. Invest New Drugs (Epub ahead of print doi:10.1007/s10637-009-9240-x) Singh M, Tyagi S, Bhui K, Prasad S, Shukla Y (2009) Regulation of cell growth through cell cycle arrest and apoptosis in HPV 16 positive human cervical cancer cells by tea polyphenols. Invest New Drugs (Epub ahead of print doi:10.​1007/​s10637-009-9240-x)
17.
go back to reference Svensson RU, Barnes JM, Rokhlin OW, Cohen MB, Henry MD (2007) Chemotherapeutic agents up-regulate the cytomegalovirus promoter: implications for bioluminescence imaging of tumor response to therapy. Cancer Res 67:10445–10454PubMedCrossRef Svensson RU, Barnes JM, Rokhlin OW, Cohen MB, Henry MD (2007) Chemotherapeutic agents up-regulate the cytomegalovirus promoter: implications for bioluminescence imaging of tumor response to therapy. Cancer Res 67:10445–10454PubMedCrossRef
18.
go back to reference Ly JD, Grubb DR, Lawen A (2003) The mitochondrial membrane potential (deltapsi(m)) in apoptosis; an update. Apoptosis 8:115–128PubMedCrossRef Ly JD, Grubb DR, Lawen A (2003) The mitochondrial membrane potential (deltapsi(m)) in apoptosis; an update. Apoptosis 8:115–128PubMedCrossRef
19.
go back to reference Ikezoe T, Chen SS, Heber D, Taguchi H, Koeffler HP (2001) Baicalin is a major component of PC-SPES which inhibits the proliferation of human cancer cells via apoptosis and cell cycle arrest. Prostate 49:285–292PubMedCrossRef Ikezoe T, Chen SS, Heber D, Taguchi H, Koeffler HP (2001) Baicalin is a major component of PC-SPES which inhibits the proliferation of human cancer cells via apoptosis and cell cycle arrest. Prostate 49:285–292PubMedCrossRef
20.
go back to reference Pidgeon GP, Kandouz M, Meram A, Honn KV (2002) Mechanisms controlling cell cycle arrest and induction of apoptosis after 12-lipoxygenase inhibition in prostate cancer cells. Cancer Res 62:2721–2727PubMed Pidgeon GP, Kandouz M, Meram A, Honn KV (2002) Mechanisms controlling cell cycle arrest and induction of apoptosis after 12-lipoxygenase inhibition in prostate cancer cells. Cancer Res 62:2721–2727PubMed
21.
go back to reference Zhang DY, Wu J, Ye F, Xue L, Jiang S, Yi J, Zhang W, Wei H, Sung M, Wang W, Li X (2003) Inhibition of cancer cell proliferation and prostaglandin E2 synthesis by Scutellaria baicalensis. Cancer Res 63:4037–4043PubMed Zhang DY, Wu J, Ye F, Xue L, Jiang S, Yi J, Zhang W, Wei H, Sung M, Wang W, Li X (2003) Inhibition of cancer cell proliferation and prostaglandin E2 synthesis by Scutellaria baicalensis. Cancer Res 63:4037–4043PubMed
22.
go back to reference Shieh DE, Cheng HY, Yen MH, Chiang LC, Lin CC (2006) Baicalin-induced apoptosis is mediated by Bcl-2-dependent, but not p53-dependent, pathway in human leukemia cell lines. Am J Chin Med 34:245–261PubMedCrossRef Shieh DE, Cheng HY, Yen MH, Chiang LC, Lin CC (2006) Baicalin-induced apoptosis is mediated by Bcl-2-dependent, but not p53-dependent, pathway in human leukemia cell lines. Am J Chin Med 34:245–261PubMedCrossRef
24.
25.
go back to reference Ma WW, Adjei AA (2009) Novel agents on the horizon for cancer therapy. CA Cancer J Clin 59:111–137PubMedCrossRef Ma WW, Adjei AA (2009) Novel agents on the horizon for cancer therapy. CA Cancer J Clin 59:111–137PubMedCrossRef
26.
27.
go back to reference Boik J (2001) Natural compounds in cancer therapy. In: Boik J (2001) Natural compounds in cancer therapy. In:
28.
go back to reference Jordan MA, Thrower D, Wilson L (1991) Mechanism of inhibition of cell proliferation by Vinca alkaloids. Cancer Res 51:2212–2222PubMed Jordan MA, Thrower D, Wilson L (1991) Mechanism of inhibition of cell proliferation by Vinca alkaloids. Cancer Res 51:2212–2222PubMed
29.
go back to reference Muggia FM, Gill I (1989) Epipodophyllotoxins: new laboratory and clinical findings. Curr Opin Oncol 1:206–212PubMed Muggia FM, Gill I (1989) Epipodophyllotoxins: new laboratory and clinical findings. Curr Opin Oncol 1:206–212PubMed
30.
go back to reference Krishan A, Paika K, Frei ER (1975) Cytofluorometric studies on the action of podophyllotoxin and epipodophyllotoxins (VM-26, VP-16-213) on the cell cycle traverse of human lymphoblasts. J Cell Biol 66:521–530PubMedCrossRef Krishan A, Paika K, Frei ER (1975) Cytofluorometric studies on the action of podophyllotoxin and epipodophyllotoxins (VM-26, VP-16-213) on the cell cycle traverse of human lymphoblasts. J Cell Biol 66:521–530PubMedCrossRef
31.
go back to reference Kingston DG, Hawkins DR, Ovington L (1982) New taxanes from Taxus brevifolia. J Nat Prod 45:466–470PubMedCrossRef Kingston DG, Hawkins DR, Ovington L (1982) New taxanes from Taxus brevifolia. J Nat Prod 45:466–470PubMedCrossRef
32.
go back to reference Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT (1971) Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc 93:2325–2327PubMedCrossRef Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT (1971) Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc 93:2325–2327PubMedCrossRef
33.
go back to reference Gunasekera SP, Badawi MM, Cordell GA, Farnsworth NR, Chitnis M (1979) Plant anticancer agents X. Isolation of camptothecin and 9-methoxycamptothecin from Ervatamia heyneana. J Nat Prod 42:475–477PubMedCrossRef Gunasekera SP, Badawi MM, Cordell GA, Farnsworth NR, Chitnis M (1979) Plant anticancer agents X. Isolation of camptothecin and 9-methoxycamptothecin from Ervatamia heyneana. J Nat Prod 42:475–477PubMedCrossRef
34.
go back to reference Schaeppi U, Fleischman RW, Cooney DA (1974) Toxicity of camptothecin (NSC-100880). Cancer Chemother Rep 3(5):25–36 Schaeppi U, Fleischman RW, Cooney DA (1974) Toxicity of camptothecin (NSC-100880). Cancer Chemother Rep 3(5):25–36
35.
go back to reference Li-Weber M (2009) New therapeutic aspects of flavones: the anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin. Cancer Treat Rev 35:57–68PubMedCrossRef Li-Weber M (2009) New therapeutic aspects of flavones: the anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin. Cancer Treat Rev 35:57–68PubMedCrossRef
36.
go back to reference Wan JY, Gong X, Zhang L, Li HZ, Zhou YF, Zhou QX (2008) Protective effect of baicalin against lipopolysaccharide/D-galactosamine-induced liver injury in mice by up-regulation of heme oxygenase-1. Eur J Pharmacol 587:302–308PubMedCrossRef Wan JY, Gong X, Zhang L, Li HZ, Zhou YF, Zhou QX (2008) Protective effect of baicalin against lipopolysaccharide/D-galactosamine-induced liver injury in mice by up-regulation of heme oxygenase-1. Eur J Pharmacol 587:302–308PubMedCrossRef
37.
go back to reference Zhang DY, Wu J, Ye F, Xue L, Jiang S, Yi J, Zhang W, Wei H, Sung M, Wang W, Li X (2003) Inhibition of cancer cell proliferation and prostaglandin E2 synthesis by Scutellaria baicalensis. Cancer Res 63:4037–4043PubMed Zhang DY, Wu J, Ye F, Xue L, Jiang S, Yi J, Zhang W, Wei H, Sung M, Wang W, Li X (2003) Inhibition of cancer cell proliferation and prostaglandin E2 synthesis by Scutellaria baicalensis. Cancer Res 63:4037–4043PubMed
38.
go back to reference Chen S, Ruan Q, Bedner E, Deptala A, Wang X, Hsieh TC, Traganos F, Darzynkiewicz Z (2001) Effects of the flavonoid baicalin and its metabolite baicalein on androgen receptor expression, cell cycle progression and apoptosis of prostate cancer cell lines. Cell Prolif 34:293–304PubMedCrossRef Chen S, Ruan Q, Bedner E, Deptala A, Wang X, Hsieh TC, Traganos F, Darzynkiewicz Z (2001) Effects of the flavonoid baicalin and its metabolite baicalein on androgen receptor expression, cell cycle progression and apoptosis of prostate cancer cell lines. Cell Prolif 34:293–304PubMedCrossRef
39.
go back to reference Chan FL, Choi HL, Chen ZY, Chan PS, Huang Y (2000) Induction of apoptosis in prostate cancer cell lines by a flavonoid, baicalin. Cancer Lett 160:219–228PubMedCrossRef Chan FL, Choi HL, Chen ZY, Chan PS, Huang Y (2000) Induction of apoptosis in prostate cancer cell lines by a flavonoid, baicalin. Cancer Lett 160:219–228PubMedCrossRef
40.
go back to reference Mori K, Kondo T, Kamiyama Y, Kano Y, Tominaga K (2003) Preventive effect of Kampo medicine (Hangeshashin-to) against irinotecan-induced diarrhea in advanced non-small-cell lung cancer. Cancer Chemother Pharmacol 51:403–406PubMed Mori K, Kondo T, Kamiyama Y, Kano Y, Tominaga K (2003) Preventive effect of Kampo medicine (Hangeshashin-to) against irinotecan-induced diarrhea in advanced non-small-cell lung cancer. Cancer Chemother Pharmacol 51:403–406PubMed
41.
go back to reference Hu Q, Noor M, Wong YF, Hylands PJ, Simmonds MS, Xu Q, Jiang D, Hendry BM, Xu Q (2009) In vitro anti-fibrotic activities of herbal compounds and herbs. Nephrol Dial Transplant 24:3033–3041PubMedCrossRef Hu Q, Noor M, Wong YF, Hylands PJ, Simmonds MS, Xu Q, Jiang D, Hendry BM, Xu Q (2009) In vitro anti-fibrotic activities of herbal compounds and herbs. Nephrol Dial Transplant 24:3033–3041PubMedCrossRef
Metadata
Title
Baicalin induces human mucoepidermoid carcinoma Mc3 cells apoptosis in vitro and in vivo
Authors
Xiao-Fang Xu
Bo-Lei Cai
Su-Min Guan
Yan Li
Jun-Zheng Wu
Yong Wang
Bin Liu
Publication date
01-08-2011
Publisher
Springer US
Published in
Investigational New Drugs / Issue 4/2011
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-010-9402-x

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