JOURNAL BROWSE
Search
Advanced SearchSearch Tips
Induction of Cell Cycle Arrest at G2/M phase by Ethanol Extract of Scutellaria baicalensis in Human Renal Cell Carcinoma Caki-1 Cells
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
  • Journal title : Herbal Formula Science
  • Volume 23, Issue 2,  2015, pp.199-208
  • Publisher : The Korean Journal of Oriental Medical Prescription
  • DOI : 10.14374/HFS.2015.23.2.199
 Title & Authors
Induction of Cell Cycle Arrest at G2/M phase by Ethanol Extract of Scutellaria baicalensis in Human Renal Cell Carcinoma Caki-1 Cells
Park, Dong-Il; Jeong, Jin-Woo; Park, Cheol; Hong, Su-Hyun; Shin, Soon-Shik; Choi, Sung-Hyun; Choi, Yung-Hyun;
  PDF(new window)
 Abstract
Objectives : In the present study, we investigated the effects of ethanol extract of Scutellaria baicalensis (EESB) on the progression of cell cycle in human renal cell carcinoma Caki-1 cells. Methods : The effects of EESB on cell growth and apoptosis induction were evaluated by trypan blue dye exclusion assay and flow cytometry, respectively. The mRNA and protein levels were determined by Western blot analysis and reverse transcription-polymerase chain reaction, respectively. Results : It was found that EESB treatment on Caki-1 cells resulted in a dose-dependent inhibition of cell growth and induced apoptotic cell death as detected by Annexin V-FITC staining. The flow cytometric analysis indicated that EESB resulted in G2/M arrest in cell cycle progression which was associated with the down-regulation of cyclin A expression. Our results also revealed that treatment with EESB increased the mRNA and proteins expression of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1), without any noticeable changes in cyclin B1, Cdk2 and Cdc2. In addition, the incubation of cells with EESB resulted in a significant increase in the binding of p21 and Cdk2 and Cdc2. These findings suggest that EESB-induced G2/M arrest and apoptosis in Caki-1 cells is mediated through the p53-mediated upregulation of Cdk inhibitor p21. Conclusions : Taken together, these findings suggest that EESB may be a potential chemotherapeutic agent and further studies will be needed to identify the biological active compounds that confer the anti-cancer activity of S. baicalensis.
 Keywords
Scutellaria baicalensis L.;renal cell carcinoma Caki-1 cells;G2/M arrest;apoptosis;p21;
 Language
Korean
 Cited by
 References
1.
Coqueret O. New roles for p21 and p27 cell-cycle inhibitors: a function for each cell compartment? Trends Cell Biol 2003; 13:65-70. crossref(new window)

2.
Bohn OL, De las Casas LE, Leon ME. Tumor-to-tumor metastasis: Renal cell carcinoma metastatic to papillary carcinoma of thyroid-report of a case and review of the literature. Head Neck Pathol 2009; 3, 327-330. crossref(new window)

3.
Motzer RJ, Bander NH, Nanus DM. Renal-cell carcinoma. N Engl J Med. 1996; 335:865-875. crossref(new window)

4.
Joniau S, Vander Eeckt K, Van Poppel H. The indications for partial nephrectomy in the treatment of renal cell carcinoma. Nat Clin Pract Urol 2006; 3: 198-205. crossref(new window)

5.
Huang Y, Tsang SY, Yao X, Chen ZY. Biological properties of baicalein in cardiovascular system. Curr Drug Targets Cardiovasc Haematol Disord 2005; 5: 177-184. crossref(new window)

6.
Lam TL, Lam ML, Au TK, Ip DT, Ng TB, Fong WP, Wan DC. A comparison of human immunodeficiency virus type-1 protease inhibition activities by the aqueous and methanol extracts of Chinese medicinal herbs. Life Sci 2000; 67: 2889-2896. crossref(new window)

7.
Jung HS, Kim MH, Gwak NG, Im YS, Lee KY, Sohn Y, Choi H, Yang WM. Antiallergic effects of Scutellaria baicalensis on inflammation in vivo and in vitro. J Ethnopharmacol 2012; 141: 345-349. crossref(new window)

8.
Lu Y, Joerger R, Wu C. Study of the chemical composition and antimicrobial activities of ethanolic extracts from roots of Scutellaria baicalensis Georgi. J Agric Food Chem 2011; 59: 10934-10942. crossref(new window)

9.
Waisundara VY, Hsu A, Huang D, Tan BK. Scutellaria baicalensis enhances the anti-diabetic activity of metformin in streptozotocin-induced diabetic Wistar rats. Am J Chin Med 2008; 36: 517-540. crossref(new window)

10.
Burnett BP, Jia Q, Zhao Y, Levy RM. A medicinal extract of Scutellaria baicalensis and Acacia catechu acts as a dual inhibitor of cyclooxygenase and 5-lipoxygenase to reduce inflammation. J Med Food 2007; 10: 442-451. crossref(new window)

11.
Gao Z, Huang K, Yang X, Xu H. Free radical scavenging and antioxidant activities of flavonoids extracted from the radix of Scutellaria baicalensis Georgi. Biochim Biophys Acta 1999; 1472: 643-650. crossref(new window)

12.
Nagai T, Suzuki Y, Tomimori T, Yamada H. Antiviral activity of plant flavonoid, 5,7,4'-trihydroxy-8-methoxyflavone, from the roots of Scutellaria baicalensis against influenza A (H3N2) and B viruses. Biol Pharm Bull 1995; 18: 295-299. crossref(new window)

13.
Woźniak D, Dryś A, Matkowski A. Antiradical and antioxidant activity of flavones from Scutellariae baicalensis radix. Nat Prod Res 2015; 29: 1567-1570. crossref(new window)

14.
Shin JW, Kang HC, Shim J, Sohn NW. Scutellaria baicalensis attenuates blood-brain barrier disruption after intracerebral hemorrhage in rats. Am J Chin Med 2012; 40: 85-96. crossref(new window)

15.
Hong GE, Kim JA, Nagappan A, Yumnam S, Lee HJ, Kim EH, Lee WS, Shin SC, Park HS, Kim GS. Flavonoids identified from Korean Scutellaria baicalensis Georgi inhibit inflammatory Signaling by Suppressing Activation of NF-κB and MAPK in RAW 264.7 Cells. Evid Based Complement Alternat Med 2013; 2013: 912031.

16.
Li C, Fong SY, Mei Q, Lin G, Zuo Z. Influence of mefenamic acid on the intestinal absorption and metabolism of three bioactive flavones in Radix Scutellariae and potential pharmacological impact. Pharm Biol 2014; 52: 291-297. crossref(new window)

17.
He X, Wei Z, Zhou E, Chen L, Kou J, Wang J, Yang Z. Baicalein attenuates inflammatory responses by suppressing TLR4 mediated NF-κB and MAPK signaling pathways in LPS-induced mastitis in mice. Int Immunopharmacol 2015; 28: 470-476. crossref(new window)

18.
Wang CZ, Li XL, Wang QF, Mehendale SR, Yuan CS. Selective fraction of Scutellaria baicalensis and its chemopreventive effects on MCF-7 human breast cancer cells. Phytomedicine 2010; 17: 63-68. crossref(new window)

19.
Gao J, Morgan WA, Sanchez-Medina A, Corcoran O. The ethanol extract of Scutellaria baicalensis and the active compounds induce cell cycle arrest and apoptosis including upregulation of p53 and Bax in human lung cancer cells. Toxicol Appl Pharmacol 2011; 254: 221-228. crossref(new window)

20.
Park KI, Park HS, Kang SR, Nagappan A, Lee DH, Kim JA, Han DY, Kim GS. Korean Scutellaria baicalensis water extract inhibits cell cycle G1/S transition by suppressing cyclin D1 expression and matrixmetalloproteinase-2 activity in human lung cancer cells. J Ethnopharmacol 2011; 133: 634-641. crossref(new window)

21.
Zhang J, Park HS, Kim JA, Hong GE, Nagappan A, Park KI, Kim GS. Flavonoids identified from Korean Scutellaria baicalensis induce apoptosis by ROS generation and caspase activation on human fibrosarcoma cells. Am J Chin Med 2014; 42: 465-483. crossref(new window)

22.
Choi BB, Choi JH, Park SR, Kim JY, Hong JW, Kim GC. Scutellariae radix induces apoptosis in chemoresistant SCC-25 human tongue squamous carcinoma cells. Am J Chin Med 2015; 43: 167-181. crossref(new window)

23.
Errico A, Deshmukh K, Tanaka Y, Pozniakovsky A, Hunt T. Identification of substrates for cyclin dependent kinases. Adv Enzyme Regul 2010; 50: 375-399. crossref(new window)

24.
Lim S, Kaldis P. Cdks, cyclins and CKIs: roles beyond cell cycle regulation. Development 2013; 140: 3079-3093. crossref(new window)

25.
Erlanson M, Landberg G. Prognostic implications of p27 and cyclin E protein contents in malignant lymphomas. Leuk Lymphoma 2001; 40: 461-470. crossref(new window)

26.
Sarita Rajender P, Ramasree D, Bhargavi K, Vasavi M, Uma V. Selective inhibition of proteins regulating CDK/cyclin complexes: strategy against cancer-a review. J Recept Signal Transduct Res 2010; 30: 206-213. crossref(new window)

27.
Raleigh JM, O’Connell MJ. The G(2) DNA damage checkpoint targets both Wee1 and Cdc25. J Cell Sci 2000; 113: 1727-1736.

28.
Sgambato A, Cittadini A, Faraglia B, Weinstein IB. Multiple functions of p27(Kip1) and its alterations in tumor cells: a review. J Cell Physiol 2000; 183: 18-27. crossref(new window)

29.
Shapiro GI, Edwards CD, Rollins BJ. The physiology of p16(INK4A)-mediated G1 proliferative arrest. Cell Biochem Biophys 2000; 33: 189-197. crossref(new window)

30.
Abbas T, Dutta A. p21 in cancer: intricate networks and multiple activities. Nat Rev Cancer 2009; 9: 400-414. crossref(new window)

31.
Cuddihy A, O'Connell M. Cell-cycle responses to DNA damage in G2. Int Rev Cytol 2003; 222: 99-140. crossref(new window)

32.
Niida H, Nakanishi M. DNA damage checkpoints in mammals. Mutagenesis 2006; 21: 3-9.

33.
Boutros R, Dozier C, Ducommun B. The when and wheres of CDC25 phosphatases. Curr Opin Cell Biol 2006; 18: 185-191. crossref(new window)