Cytotoxicity and radiosensitizing effect of wogonin, an extract from Scutellaria litwinowii, in head and neck squamous cell carcinoma line HN5
Keywords:
Cytotoxicity; HN5 cell line; Radiosensitizing; Squamous cell of head and neck; WogoninAbstract
Background: Radiotherapy is one of the most prominent techniques used in cancer therapy. However, efforts for finding new effective radiosensitizers in improvement of radiotherapy efficacy have been continued yet. Wogonin is a natural flavonoid from Scutellaria litwinowii with known cytotoxic effects in some cancer cells. Objective: To determine the potential of radiosensitizer effects of wogonin in a head and neck cancer cell line (HN5). Methods: This study was carried out in Omid Hospital and Herbal Medicine Research Center (Mashhad, Iran). HN5 cells were cultured in DMEM medium and incubated with different concentrations of wogonin (25-500 µg/ml) and were exposed to (2-10 Gray [Gy]) γ-rays. Cell viability was quantified by MTT assay in wogonin cytotoxicity assay after 24, 48 and 72 hours and in coincident radiation and wogonin therapy after 72 hours. Data were analyzed by performing one-way ANOVA in SPSS (V.16). P-value ≤ 0.05 was considered significant. Results: Wogonin decreased cell viability in HN5 cells as a time- and concentration-dependent manner. Wogonin could also enhance radiation-induced toxicity. For instance, while cell viability percentage in separate administration of wogonin (100 µM) and radiation (2 Gy) was significantly decreased to 53.98±2.76 and 74.97±1.05 respectively (p<0.001), wogonin 100 µM concurrent with 2 Gy radiation decreased the percentage of cell viability to 33.29±1.76 (p<0.001). Conclusion: Concurrent use of wogonin and radiation increased radiation sensitivity and cell death in HN5 cells. Therefore, wogonin is a good radiosensitizer candidate for more study.References
Joshi P, Dutta S, Chaturvedi P, Nair S. Head and neck cancers in developing countries. Rambam
Maimonides medical journal. 2014; 5(2): e0009. doi: 10.5041/RMMJ.10143. PMID: 24808947, PMCID:
PMC4011474.
Mirzaei M, Hosseini S-A, Ghoncheh M, Soheilipour F, Soltani S, Soheilipour F, et al. Epidemiology and
trend of head and neck cancers in Iran. Global journal of health science. 2016; 8(1): 189. PMID: 26234980,
PMCID: PMC4803954.
Sanderson R, Ironside J. Squamous cell carcinomas of the head and neck. BMJ: British Medical Journal.
; 325(7368): 822-827. PMID: 12376446, PMCID: PMC1124330.
Singh B, Kim SH, Carew JF, Yu I, Shaha AR, Wolden S, et al. Genome-wide screening for radiation
response factors in head and neck cancer. The Laryngoscope. 2000; 110(8): 1251-6. doi:
1097/00005537-200008000-00005. PMID: 10942121.
Simstein R, Burow M, Parker A, Weldon C, Beckman B. Apoptosis, chemoresistance, and breast cancer:
insights from the MCF-7 cell model system. Experimental biology and medicine. 2003; 228(9): 995-1003.
PMID: 14530507.
Liauw SL, Connell PP, Weichselbaum RR. New paradigms and future challenges in radiation oncology: an
update of biological targets and technology. Science translational medicine. 2013; 5(173): 173sr2-sr2. doi:
1126/scitranslmed.3005148. PMID: 23427246, PMCID: PMC3769139.
Tai MC, Tsang SY, Chang LY, Xue H. Therapeutic potential of wogonin: a naturally occurring flavonoid.
CNS drug reviews. 2005 Summer; 11(2): 141-50. PMID: 16007236.
Li-Weber M. New therapeutic aspects of flavones: the anticancer properties of Scutellaria and its main
active constituents Wogonin, Baicalein and Baicalin. Cancer treatment reviews. 2009 Feb; 35(1): 57-68.
doi: 10.1016/j.ctrv.2008.09.005. PMID: 19004559.
Himeji M, Ohtsuki T, Fukazawa H, Tanaka M, Yazaki S, Ui S, et al. Difference of growth-inhibitory effect
of Scutellaria baicalensis-producing flavonoid wogonin among human cancer cells and normal diploid cell.
Cancer letters. 2007 Jan 245(1-2): 269-74. doi: 10.1016/j.canlet.2006.01.011. PMID: 16497434.
Polier G, Ding J, Konkimalla BV, Eick D, Ribeiro N, Kohler R, et al. Wogonin and related natural flavones
are inhibitors of CDK9 that induce apoptosis in cancer cells by transcriptional suppression of Mcl-1. Cell
death & disease. 2011 Jul 21; 2: e182. doi: 10.1038/cddis.2011.66. PMID: 21776020, PMCID:
PMC3199715.
Chung H, Jung YM, Shin DH, Lee JY, Oh MY, Kim HJ, et al. Anticancer effects of wogonin in both
estrogen receptor-positive and -negative human breast cancer cell lines in vitro and in nude mice
xenografts. International journal of cancer. 2008; 122(4): 816-22. doi: 10.1002/ijc.23182. PMID:
Lee DH, Kim C, Zhang L, Lee YJ. Role of p53, PUMA, and Bax in wogonin-induced apoptosis in human
cancer cells. Biochemical pharmacology. 2008; 75(10): 2020-33. doi: 10.1016/j.bcp.2008.02.023. PMID:
, PMCID: PMC2424318.
Tayarani-Najarani Z, Asili J, Parsaee H, Mousavi SH, Mashhadian NV, Mirzaee A, et al. Wogonin and
neobaicalein from Scutellaria litwinowii roots are apoptotic for HeLa cells. Rev. bras. farmacogn. 2012;
(2): 268-76. doi: 10.1590/S0102-695X2011005000161.
Dayal R, Singh A, Pandey A, Mishra KP. Reactive oxygen species as mediator of tumor radiosensitivity.
Journal of cancer research and therapeutics. 2014; 10(4): 811-8. doi: 10.4103/0973-1482.146073. PMID:
Cole IB, Cao J, Alan AR, Saxena PK, Murch SJ. Comparisons of Scutellaria baicalensis, Scutellaria
lateriflora and Scutellaria racemosa: genome size, antioxidant potential and phytochemistry. Planta medica.
; 74(04): 474-81. doi: 10.1055/s-2008-1034358. PMID: 18484546.
Mousavi SH, Tavakkol-Afshari J, Brook A, Jafari-Anarkooli I. Role of caspases and Bax protein in saffroninduced apoptosis in MCF-7 cells. Food and chemical toxicology : an international journal published for
the British Industrial Biological Research Association. 2009; 47(8): 1909-13. doi:
1016/j.fct.2009.05.017. PMID: 19457443.
Magne N, Fischel JL, Dubreuil A, Formento P, Marcie S, Lagrange JL, et al. Sequence-dependent effects
of ZD1839 ('Iressa') in combination with cytotoxic treatment in human head and neck cancer. British
journal of cancer. 2002; 86(5): 819-27. doi: 10.1038/sj.bjc.6600103. PMID: 11875748.
Torres MA, Raju U, Molkentine D, Riesterer O, Milas L, Ang KK. AC480, formerly BMS-599626, a pan
Her inhibitor, enhances radiosensitivity and radioresponse of head and neck squamous cell carcinoma cells
in vitro and in vivo. Investigational new drugs. 2011; 29(4): 554-61. doi: 10.1007/s10637-010-9389-3.
PMID: 20119866.
Da Rocha AB, Lopes RM, Schwartsmann G. Natural products in anticancer therapy. Current Opinion in
Pharmacology. 2001; 1(4): 364-9. PMID: 11710734.
Hseu YC, Chen SC, Chen HC, Liao JW, Yang HL. Antrodia camphorata inhibits proliferation of human
breast cancer cells in vitro and in vivo. Food and chemical toxicology : an international journal published
for the British Industrial Biological Research Association. 2008; 46(8): 2680-8. doi:
1016/j.fct.2008.04.036. PMID: 18550246.
Huang P, Feng L, Oldham EA, Keating MJ, Plunkett W. Superoxide dismutase as a target for the selective
killing of cancer cells. Nature. 2000; 407(6802): 390-5. doi: 10.1038/35030140. PMID: 11014196.
Zhang L, Tao L, Ruan J, Li W, Wu Y, Yan L, et al. Xanthatin induces G2/M cell cycle arrest and apoptosis
in human gastric carcinoma MKN-45 cells. Planta medica. 2012; 78(9): 890-5. doi: 10.1055/s-0031- 1298481. PMID: 22532019.
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. Journal of medicinal
food. 2007; 10(3): 442-51. doi: 10.1089/jmf.2006.255. PMID: 17887937.
Parajuli P, Joshee N, Rimando AM, Mittal S, Yadav AK. In vitro antitumor mechanisms of various
Scutellaria extracts and constituent flavonoids. Planta medica. 2009; 75(1): 41-8. doi: 10.1055/s-0028- 1088364. PMID: 19031366.
Zhang Y, Wang X, Wang X, Xu Z, Liu Z, Ni Q, et al. Protective effect of flavonoids from Scutellaria
baicalensis Georgi on cerebral ischemia injury. Journal of ethnopharmacology. 2006; 108(3): 355-60. doi:
1016/j.jep.2006.05.022. PMID: 16829002.
Ye F, Wang H, Jiang S, Wu J, Shao J, Cheng X, et al. Quality evaluation of commercial extracts of
Scutellaria baicalensis. Nutrition and cancer. 2004; 49(2): 217-22. doi: 10.1207/s15327914nc4902_14.
PMID: 15489215.
Sonoda M, Nishiyama T, Matsukawa Y, Moriyasu M. Cytotoxic activities of flavonoids from two
Scutellaria plants in Chinese medicine. Journal of ethnopharmacology. 2004; 91(1): 65-8. doi:
1016/j.jep.2003.11.014. PMID: 15036470.
Malikov V, Yuldashev M. Phenolic compounds of plants of the Scutellaria L. genus. Distribution,
structure, and properties. Chem. Nat. Compd. 2002; 38(4): 358-406.
Tayarani-Najaran Z, Mousavi SH, Vahdati-Mashhadian N, Emami SA, Parsaee H. Scutellaria litwinowii
induces apoptosis through both extrinsic and intrinsic apoptotic pathways in human promyelocytic
leukemia cells. Nutrition and cancer. 2012; 64(1): 80-8. doi: 10.1080/01635581.2012.630162. PMID:
Sharma N, Singh AK, Sodhi SS, ZHANG J-J, Mongre RK, Ghosh M, et al. Anti-tumor activity of wogonin,
an extract from Scutellaria baicalensis, through regulating different signaling pathways. Chinese Journal of
Natural Medicines. 2017; 15(1): 15-40. doi: 10.1016/S1875-5364(17)30005-5. PMID: 28259249.
Shojaee S, Parhiz H, Eshaghi A, Emami SA, Asili J, Behravan J, et al. In vitro protective effects of
Scutellaria litwinowii root extract against H2O2-induced DNA damage and cytotoxicity. Journal of
Complementary and Integrative Medicine. 2014; 11(2): 121-7. doi: 10.1515/jcim-2014-0009. PMID:
Milas L, Mason K, Hunter N, Petersen S, Yamakawa M, Ang K, et al. In vivo enhancement of tumor
radioresponse by C225 antiepidermal growth factor receptor antibody. Clinical cancer research : an official
journal of the American Association for Cancer Research. 2000; 6(2): 701-8. PMID: 10690556.
Sano D, Matsumoto F, Valdecanas DR, Zhao M, Molkentine DP, Takahashi Y, et al. Vandetanib restores
head and neck squamous cell carcinoma cells' sensitivity to cisplatin and radiation in vivo and in vitro.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2011; 17(7):
-27. doi: 10.1158/1078-0432.CCR-10-2120. PMID: 21350000. PMCID: PMC3074405.
Afsharzadeh M, Tayarani-Najaran Z, Zare A, Mousavi SH. Protective effect of Scutellaria litwinowii
extract on serum/glucose-deprived cultured PC12 cells and determining the role of reactive oxygen species.
Journal of toxicology. 2012; 2012. doi: 10.1155/2012/413279. PMID: 22888343, PMCID: PMC3409551.
Downloads
Published
Issue
Section
License
Copyright (c) 2020 KNOWLEDGE KINGDOM PUBLISHING
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
