Published March 12, 2024 | Version v1
Journal article Open

Study of the antitumor activity of the combination baicalin and epigallocatechin gallate in a murine model of vincristine-resistant breast cancer

  • 1. Applied Science Private University, Amman, Jordan
  • 2. The University of Jordan, Amman, Jordan

Description

Background: Breast cancer is one of the primary causes of death in women worldwide. Yearly, a quarter of cancer cases in women are breast cancer. The problem is aggravated by the emergence of chemotherapeutic resistance. One of the practices to overcome this problem is using natural products along with chemotherapy. Epigallocatechin Gallate (EGCG) is the main efficient catechin in green tea. Baicalin is the main active chemical constituent of Scutellaria baicalensis. Both natural products have anti-cancer and improving resistance activities. Therefore, a combination of EGCG and baicalin may afford a possible way out to overcome chemotherapeutic resistance.

Methods: EGCG and baicalin were tested on Vincristine-sensitive (EMT-6/P) and Vincristine-resistant (EMT-6/V) mouse mammary cell lines. Antiproliferative and apoptotic effects were assessed for EGCG, baicalin, their combination, and Vincristine in vitro using MTT and caspase-3 assays. An in vivo study was conducted to assess the effect of EGCG, baicalin, their combination, vincristine, vincristine along with the combination in both EMT-6/P and EMT-6/V mouse mammary cell lines. The safety profile was also considered using liver enzymes and creatinine assays.

Results: in vitro, EGCG and baicalin had synergistic effects in both cell lines. The combination of baicalin and EGCG as 140 and 100 µM respectively, caused an apoptotic effect higher than the single treatment of baicalin 175 µM or EGCG 125 µM, in vincristine-resistant cell lines. In vivo, the combination along with vincristine significantly enhanced the reduction of tumour size in mice implanted with EMT-6/P and EMT-6/V cell lines. According to the safety profile, the combinations of EGCG and baicalin are safe.

Conclusion: The combination of baicalin and EGCG can be optimistic in improving vincristine-resistant cells to treatments.

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References

  • Aggarwal V, Tuli HS, Tania M, Srivastava S, Ritzer EE, Pandey A, Aggarwal D, Barwal TS, Jain A, Kaur G (2022) Molecular mechanisms of action of epigallocatechin gallate in cancer: Recent trends and advancement. Seminars in Cancer Biology 80: 256–275. https://doi.org/10.1016/j.semcancer.2020.05.011
  • Ahn WS, Huh SW, Bae S-M, Lee IP, Lee JM, Namkoong SE, Kim CK, Sin J-I (2003) A major constituent of green tea, EGCG, inhibits the growth of a human cervical cancer cell line, CaSki cells, through apoptosis, G1 arrest, and regulation of gene expression. DNA and Cell Biology 22: 217–224. https://doi.org/10.1089/104454903321655846
  • Arnold M, Morgan E, Rumgay H, Mafra A, Singh D, Laversanne M, Vignat J, Gralow JR, Cardoso F, Siesling S (2022) Current and future burden of breast cancer: Global statistics for 2020 and 2040. The Breast 66: 15–23. https://doi.org/10.1016/j.breast.2022.08.010
  • Braicu C, Gherman CD, Irimie A, Berindan-Neagoe I (2013) Epigallocatechin-3-Gallate (EGCG) inhibits cell proliferation and migratory behaviour of triple negative breast cancer cells. Journal of Nanoscience and Nanotechnology 13: 632–637. https://doi.org/10.1166/jnn.2013.6882
  • Chan FL, Choi HL, Chen ZY, Chan PSF, Huang Y (2000) Induction of apoptosis in prostate cancer cell lines by a flavonoid, baicalin. Cancer Letters 160: 219–228. https://doi.org/10.1016/S0304-3835(00)00591-7
  • Chen F, Zhuang M, Zhong C, Peng J, Wang X, Li J, Chen Z, Huang YJOr (2015) Baicalein reverses hypoxia-induced 5-FU resistance in gastric cancer AGS cells through suppression of glycolysis and the PTEN/Akt/HIF-1α signaling pathway. Oncology Reports 33: 457–463. https://doi.org/10.3892/or.2014.3550
  • Chen J, Li Z, Chen AY, Ye X, Luo H, Rankin GO, Chen YC (2013a) Inhibitory effect of baicalin and baicalein on ovarian cancer cells. International Journal of Molecular Sciences 14: 6012–6025. https://doi.org/10.3390/ijms14036012
  • Chen L, Guo X, Hu Y, Li L, Liang G, Zhang GJFOb (2020) Epigallocatechin‐3‐gallate sensitises multidrug‐resistant oral carcinoma xenografts to vincristine sulfate. FEBS Open bio 10: 1403–1413. https://doi.org/10.1002/2211-5463.12905
  • Chen L, Ye H-L, Zhang G, Yao W-M, Chen X-Z, Zhang F-C, Liang GJPo (2014) Autophagy inhibition contributes to the synergistic interaction between EGCG and doxorubicin to kill the hepatoma Hep3B cells. PLOS ONE 9: e85771. https://doi.org/10.1371/journal.pone.0085771
  • Chen W-C, Kuo T-H, Tzeng Y-S, Tsai Y-C (2012) Baicalin induces apoptosis in SW620 human colorectal carcinoma cells in vitro and suppresses tumor growth in vivo. Molecules 17: 3844–3857. https://doi.org/10.3390/molecules17043844
  • Chen Y-J, Wu C-S, Shieh J-J, Wu J-H, Chen H-Y, Chung T-W, Chen Y-K, Lin C-C (2013b) Baicalein triggers mitochondria-mediated apoptosis and enhances the antileukemic effect of vincristine in childhood acute lymphoblastic leukemia CCRF-CEM cells. Evidence-Based Complementary 2013: 124747. https://doi.org/10.1155/2013/124747
  • Chen Y, Zhang J, Zhang M, Song Y, Zhang Y, Fan S, Ren S, Fu L, Zhang N, Hui H (2021) Baicalein resensitizes tamoxifen‐resistant breast cancer cells by reducing aerobic glycolysis and reversing mitochondrial dysfunction via inhibition of hypoxia‐inducible factor‐1α. Clinical and Translational Medicine 11: e577. https://doi.org/10.1002/ctm2.577
  • Cragg GM, Pezzuto JM (2016) Natural products as a vital source for the discovery of cancer chemotherapeutic and chemopreventive agents. Medical Principles and Practice 25: 41–59. https://doi.org/10.1159/000443404
  • D'Angelo L, Piazzi G, Pacilli A, Prossomariti A, Fazio C, Montanaro L, Graziani G, Fogliano V, Munarini A, Bianchi FJC (2014) A combination of eicosapentaenoic acid-free fatty acid, epigallocatechin-3-gallate and proanthocyanidins has a strong effect on mTOR signaling in colorectal cancer cells. Carcinogenesis 35(10): 2314–2320. https://doi.org/10.1093/carcin/bgu173
  • Datta S, Sinha D (2019) EGCG maintained Nrf2-mediated redox homeostasis and minimized etoposide resistance in lung cancer cells. Journal of Functional Foods 62: 103553. https://doi.org/10.1016/j.jff.2019.103553
  • de Albuquerque Souza JV, Gonçalves FDM, Lira-Junior ACOG, Escodro PB, Cãmara DR, Notomi MK (2022) Vincristine sulfate treatment influence on kidney function of female dogs with transmissible venereal tumor. Brazilian Journal of Veterinary Research and Animal Science 59: e192646–e192646. https://doi.org/10.11606/issn.1678-4456.bjvras.2022.192646
  • Demain AL, Vaishnav PJMb (2011) Natural products for cancer chemotherapy. Microbial Biotechnology 4: 687–699. https://doi.org/10.1111/j.1751-7915.2010.00221.x
  • Dou J, Wang Z, Ma L, Peng B, Mao K, Li C, Su M, Zhou C, Peng G (2018) Baicalein and baicalin inhibit colon cancer using two distinct fashions of apoptosis and senescence. Oncotarget 9: 20089. https://doi.org/10.18632/oncotarget.24015
  • Druesne-Pecollo N, Touvier M, Barrandon E, Chan DS, Norat T, Zelek L, Hercberg S, Latino-Martel P (2012) Excess body weight and second primary cancer risk after breast cancer: a systematic review and meta-analysis of prospective studies. Breast Cancer Research 135: 647–654. https://doi.org/10.1007/s10549-012-2187-1
  • Du G, Han G, Zhang S, Lin H, Wu X, Wang M, Ji L, Lu L, Yu L, Liang W (2010) Baicalin suppresses lung carcinoma and lung metastasis by SOD mimic and HIF-1α inhibition. European Journal of Pharmacology 630: 121–130. https://doi.org/10.1016/j.ejphar.2009.12.014
  • Du GJ, Wang CZ, Qi LW, Zhang ZY, Calway T, He TC, Du W, Yuan CSJPR (2013) The synergistic apoptotic interaction of panaxadiol and epigallocatechin gallate in human colorectal cancer cells. Phytotherapy Research 27: 272–277. https://doi.org/10.1002/ptr.4707
  • Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M, Znaor A, Bray FJIjoc (2021) Cancer statistics for the year 2020: An overview. International Journal of Cancer 149: 778–789. https://doi.org/10.1002/ijc.33588
  • Franek KJ, Zhou Z, Zhang W-D, Chen WY (2005) In vitro studies of baicalin alone or in combination with Salvia miltiorrhiza extract as a potential anti-cancer agent. International Journal of Oncology 26: 217–224. https://doi.org/10.3892/ijo.26.1.217
  • Gao C, Zhou Y, Li H, Cong X, Jiang Z, Wang X, Cao R, Tian W (2017) Antitumor effects of baicalin on ovarian cancer cells through induction of cell apoptosis and inhibition of cell migration in vitro. Molecular Medicine Reports 16: 8729–8734. https://doi.org/10.3892/mmr.2017.7757
  • Gao Y, Liu H, Wang H, Hu H, He H, Gu N, Han X, Guo Q, Liu D, Cui S (2018) Baicalin inhibits breast cancer development via inhibiting IĸB kinase activation in vitro and in vivo. International Journal of Oncology 53: 2727–2736. https://doi.org/10.3892/ijo.2018.4594
  • Ghosh S, Lalani R, Maiti K, Banerjee S, Bhatt H, Bobde YS, Patel V, Biswas S, Bhowmick S, Misra A (2021) Synergistic co-loading of vincristine improved chemotherapeutic potential of pegylated liposomal doxorubicin against triple negative breast cancer and non-small cell lung cancer. Nanomedicine: Nanotechnology, Biology and Medicine 31: 102320. https://doi.org/10.1016/j.nano.2020.102320
  • Gray AL, Stephens CA, Bigelow RLH, Coleman DT, Cardelli JA (2014) The polyphenols (–)-epigallocatechin-3-gallate and luteolin synergistically inhibit TGF-β-induced myofibroblast phenotypes through RhoA and ERK inhibition. PLOS ONE 9: e109208. https://doi.org/10.1371/journal.pone.0109208
  • Gu JJ, Qiao KS, Sun P, Chen P, Li Q (2018) Study of EGCG induced apoptosis in lung cancer cells by inhibiting PI3K/Akt signaling pathway. European Review for Medical and Pharmacological Sciences 22: 4557–4563.
  • Heyza JR, Arora S, Zhang H, Conner KL, Lei W, Floyd AM, Deshmukh RR, Sarver J, Trabbic CJ, Erhardt P (2018) Targeting the DNA repair endonuclease ERCC1-XPF with green tea polyphenol epigallocatechin-3-gallate (EGCG) and its prodrug to enhance cisplatin efficacy in human cancer cells. Nutrients 10: 1644. https://doi.org/10.3390/nu10111644
  • Hortobagyi GN, de la Garza Salazar J, Pritchard K, Amadori D, Haidinger R, Hudis CA, Khaled H, Liu M-C, Martin M, Namer M, O'Shaughnessy JA, Shen ZZ, Albain KS (2005) The global breast cancer burden: variations in epidemiology and survival. Clinical Breast Cancer 6: 391–401. https://doi.org/10.3816/CBC.2005.n.043
  • Hou Y, Pi C, Feng X, Wang Y, Fu S, Zhang X, Zhao L, Wei Y (2020) Antitumor activity in vivo and vitro of new chiral derivatives of baicalin and induced apoptosis via the PI3K/Akt signaling pathway. Molecular Therapy-Oncolytics 19: 67–78. https://doi.org/10.1016/j.omto.2020.08.018
  • Hu Y, Chen L, Zhang G, Li L, Liang G (2017) Epigallocatechin‐3‐gallate sensitizes multidrug‐resistant oral squamous carcinoma cells to vincristine sulfate involving angiogenesis inhibition via down‐regulating VEGF in vivo. The FASEB Journal 31: 790–720. https://doi.org/10.1096/fasebj.31.1_supplement.790.20
  • Hua F, Xiao Y-Y, Qu X-H, Li S-S, Zhang K, Zhou C, He J-L, Zhu Y, Wan Y-Y, Jiang L-P (2022) Baicalein sensitizes triple negative breast cancer MDA-MB-231 cells to doxorubicin via autophagy-mediated down-regulation of CDK1. Molecular and Cellular Biochemistry 478(7): 1519–1531. https://doi.org/10.1007/s11010-022-04597-9
  • Huang C-Y, Han Z, Li X, Xie H-H, Zhu S-SJ (2017) Mechanism of EGCG promoting apoptosis of MCF-7 cell line in human breast cancer. Oncology Letters 14: 3623–3627. https://doi.org/10.3892/ol.2017.6641
  • Huang T, Liu Y, Zhang C (2019) Pharmacokinetics and bioavailability enhancement of baicalin: a review. European Journal of Drug Metabolism and Pharmacokinetics 44: 159–168. https://doi.org/10.1007/s13318-018-0509-3
  • Ichite N, Chougule MB, Jackson T, Fulzele SV, Safe S, Singh M (2009) Enhancement of docetaxel anticancer activity by a novel diindolylmethane compound in human non-small cell lung cancer. Clinical Cancer Research 15: 543–552. https://doi.org/10.1158/1078-0432.CCR-08-1558
  • Kim K-C, Lee C (2014) Reversal of Cisplatin resistance by epigallocatechin gallate is mediated by downregulation of axl and tyro 3 expression in human lung cancer cells. Korean Journal of Physiology & Pharmacology 18(1): 61–66. https://doi.org/10.4196/kjpp.2014.18.1.61
  • Kong N, Chen X, Feng J, Duan T, Liu S, Sun X, Chen P, Pan T, Yan L, Jin TJAPSB (2021) Baicalin induces ferroptosis in bladder cancer cells by downregulating FTH1. Acta Pharmaceutica Sinica B 11(12): 4045–4054. https://doi.org/10.1016/j.apsb.2021.03.036
  • Kostin SF, McDonald DE, McFadden DW (2012) Inhibitory effects of (-)-epigallocatechin-3-gallate and pterostilbene on pancreatic cancer growth in vitro. Journal of Surgical Research 177: 255–262. https://doi.org/10.1016/j.jss.2012.04.023
  • Kumar A, Jaitak V (2019) Natural products as multidrug resistance modulators in cancer. European Journal of Medicinal Chemistry 176: 268–291. https://doi.org/10.1016/j.ejmech.2019.05.027
  • Landis-Piwowar KR, Huo C, Chen DI, Milacic V, Shi G, Chan TH, Dou QP (2007) A novel prodrug of the green tea polyphenol (–)-epigallocatechin-3-gallate as a potential anticancer agent. Cancer Research 67: 4303–4310. https://doi.org/10.1158/0008-5472.CAN-06-4699
  • Lang M, Henson R, Braconi C, Patel T (2009) Epigallocatechin‐gallate modulates chemotherapy‐induced apoptosis in human cholangiocarcinoma cells. Liver International 29: 670–677. https://doi.org/10.1111/j.1478-3231.2009.01984.x
  • Lee J-H, Jeong Y-J, Lee S-W, Kim D, Oh S-J, Lim H-S, Oh H-K, Kim S-H, Kim W-J, Jung J-Y (2010) EGCG induces apoptosis in human laryngeal epidermoid carcinoma Hep2 cells via mitochondria with the release of apoptosis-inducing factor and endonuclease G. Cancer Letters 290: 68–75. https://doi.org/10.1016/j.canlet.2009.08.027
  • Lee T-C, Cheng IC, Shue J-J, Wang TC (2011) Cytotoxicity of arsenic trioxide is enhanced by (–)-epigallocatechin-3-gallate via suppression of ferritin in cancer cells. Toxicology and Applied Pharmacology 250: 69–77. https://doi.org/10.1016/j.taap.2010.10.005
  • Li J, Duan B, Guo Y, Zhou R, Sun J, Bie B, Yang S, Huang C, Yang J, Li Z (2018) Baicalein sensitizes hepatocellular carcinoma cells to 5-FU and Epirubicin by activating apoptosis and ameliorating P-glycoprotein activity. Biomedicine & Pharmacotherapy 98: 806–812. https://doi.org/10.1016/j.biopha.2018.01.002
  • Lin M-Y, Cheng W-T, Cheng H-C, Chou W-C, Chen H-I, Ou H-C, Tsai K-LJA (2021) Baicalin enhances chemosensitivity to doxorubicin in breast cancer cells via upregulation of oxidative stress-mediated mitochondria-dependent apoptosis. Antioxidants 10: 1506. https://doi.org/10.3390/antiox10101506
  • Liu D-K, Dong H-F, Liu R-F, Xiao X-L (2020) Baicalin inhibits the TGF-β1/p-Smad3 pathway to suppress epithelial-mesenchymal transition-induced metastasis in breast cancer. Oncotarget 11: 2863. https://doi.org/10.18632/oncotarget.27677
  • Lukaszewicz K, Wtorek J, Bujnowski A, Skokowski J (2010) Monitoring of breast tissue thermo-ablation by means of impedance measurements. In: Journal of Physics: Conference Series. IOP Publishing, Journal of Physics: Conference Series 224: 012136. https://doi.org/10.1088/1742-6596/224/1/012136
  • Luo K-W, Chen W, Lung W-Y, Wei X-Y, Cheng B-H, Cai Z-M, Huang W-R (2017) EGCG inhibited bladder cancer SW780 cell proliferation and migration both in vitro and in vivo via down-regulation of NF-κB and MMP-9. The Journal of Nutritional Biochemistry 41: 56–64. https://doi.org/10.1016/j.jnutbio.2016.12.004
  • Ma W, Liu X, Du WJA-cd (2019) Baicalin induces apoptosis in SW480 cells through downregulation of the SP1 transcription factor. Anti-Cancer Drugs 30: 153. https://doi.org/10.1097/CAD.0000000000000708
  • Mansoori B, Mohammadi A, Davudian S, Shirjang S, Baradaran BJApb (2017) The different mechanisms of cancer drug resistance: a brief review. Advanced Pharmaceutical Bulletin 7: 339. https://doi.org/10.15171/apb.2017.041
  • National Institute of D, Digestive, Kidney D (2012) LiverTox: clinical and research information on drug-induced liver injury. National Institute of Diabetes and Digestive and Kidney Diseases.
  • Newman DJ, Cragg GM (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010. Journal of Natural Products 75: 311–335. https://doi.org/10.1021/np200906s
  • Niu Y, Na L, Feng R, Gong L, Zhao Y, Li Q, Li Y, Sun C (2013) The phytochemical, EGCG, extends lifespan by reducing liver and kidney function damage and improving age‐associated inflammation and oxidative stress in healthy rats. Aging Cell 12: 1041–1049. https://doi.org/10.1111/acel.12133
  • Papi A, Farabegoli F, Iori R, Orlandi M, De Nicola GR, Bagatta M, Angelino D, Gennari L, Ninfali P (2013) Vitexin-2-O-xyloside, raphasatin and (–)-epigallocatechin-3-gallate synergistically affect cell growth and apoptosis of colon cancer cells. Food Chemistry 138: 1521–1530. https://doi.org/10.1016/j.foodchem.2012.11.112
  • Peng Y, Fu Z-z, Guo C-S, Zhang Y-X, Di Y, Jiang B, Li Q-W (2015) Effects and mechanism of baicalin on apoptosis of cervical cancer HeLa cells in-vitro. Iranian Journal of Pharmaceutical Research 14: 251.
  • Ponte LGS, Pavan ICB, Mancini MCS, da Silva LGS, Morelli AP, Severino MB, Bezerra RMN, Simabuco FM (2021) The hallmarks of flavonoids in cancer. Molecules 26: 2029. https://doi.org/10.3390/molecules26072029
  • Rahib L, Wehner MR, Matrisian LM, Nead KTJJno (2021) Estimated projection of US cancer incidence and death to 2040. JAMA network open 4: e214708-e214708. https://doi.org/10.1001/jamanetworkopen.2021.4708
  • Rahman AA, Makpol S, Jamal R, Harun R, Mokhtar N, Wan Ngah WZJM (2014) Tocotrienol-rich fraction,[6]-gingerol and epigallocatechin gallate inhibit proliferation and induce apoptosis of glioma cancer cells. Molecules 19(9): 14528–14541. https://doi.org/10.3390/molecules190914528
  • Roomi MW, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M (2005) In vivo antitumor effect of ascorbic acid, lysine, proline and green tea extract on human prostate cancer PC-3 xenografts in nude mice: Evaluation of tumor growth and immunohistochemistry. Oncology Reports 13(3): 421–425. https://doi.org/10.3892/or.13.3.421
  • Sen T, Dutta A, Chatterjee A (2010) Epigallocatechin-3-gallate (EGCG) downregulates gelatinase-B (MMP-9) by involvement of FAK/ERK/NFκB and AP-1 in the human breast cancer cell line MDA-MB-231. Anti-Cancer Drugs 21: 632–644. https://doi.org/10.1097/CAD.0b013e32833a4385
  • Shankar S, Ganapathy S, Hingorani SR, Srivastava RK (2008) EGCG inhibits growth, invasion, angiogenesis and metastasis of pancreatic cancer. Frontiers in Bioscience: a Journal and Virtual Library 13: 440–452. https://doi.org/10.2741/2691
  • Shati AA (2019) Sub-chronic administration of vincristine sulfate induces renal damage and apoptosis in rats via induction of oxidative stress and activation of Raf1-MEK1/2-Erk1/2 signal transduction. International Journal of Morphology 37(1): 273–283. https://doi.org/10.4067/S0717-95022019000100273
  • Shervington A, Pawar V, Menon S, Thakkar D, Patel R (2009) The sensitization of glioma cells to cisplatin and tamoxifen by the use of catechin. Molecular Biology Reports 36: 1181–1186. https://doi.org/10.1007/s11033-008-9295-3
  • Shieh D-E, Cheng H-Y, Yen M-H, Chiang L-C, Lin C-C (2006) Baicalin-induced apoptosis is mediated by Bcl-2-dependent, but not p53-dependent, pathway in human leukemia cell lines. The American Journal of Chinese Medicine 34: 245–261. https://doi.org/10.1142/S0192415X06003801
  • Singh S, Meena A, Luqman S (2021) Baicalin mediated regulation of key signaling pathways in cancer. Pharmacological Research 164: 105387. https://doi.org/10.1016/j.phrs.2020.105387
  • Sui X, Han X, Chen P, Wu Q, Feng J, Duan T, Chen X, Pan T, Yan L, Jin T (2021) Baicalin induces apoptosis and suppresses the cell cycle progression of lung cancer cells through downregulating Akt/mTOR signaling pathway. Frontiers in Molecular Biosciences 7: 602282. https://doi.org/10.3389/fmolb.2020.602282
  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a Cancer Journal for Clinicians 71: 209–249. https://doi.org/10.3322/caac.21660
  • Talib WH (2020) A ketogenic diet combined with melatonin overcomes cisplatin and vincristine drug resistance in breast carcinoma syngraft. Nutrition 72: 110659. https://doi.org/10.1016/j.nut.2019.110659
  • Talib WH, Awajan D, Hamed RA, Azzam AO, Mahmod AI, Al-Yasari IH (2022a) Combination anticancer therapies using selected phytochemicals. Molecules 27: 5452. https://doi.org/10.3390/molecules27175452
  • Talib WH, Daoud S, Mahmod AI, Hamed RA, Awajan D, Abuarab SF, Odeh LH, Khater S, Al Kury LTJM (2022b) Plants as a source of anticancer agents: From bench to bedside. Molecules 27: 4818. https://doi.org/10.3390/molecules27154818
  • Thangapazham RL, Singh AK, Sharma A, Warren J, Gaddipati JP, Maheshwari RK (2007) Green tea polyphenols and its constituent epigallocatechin gallate inhibits proliferation of human breast cancer cells in vitro and in vivo. Cancer Letters 245: 232–241. https://doi.org/10.1016/j.canlet.2006.01.027
  • Tsubaki M, Takeda T, Ogawa N, Sakamoto K, Shimaoka H, Fujita A, Itoh T, Imano M, Ishizaka T, Satou T, Nishida S (2015) Overexpression of survivin via activation of ERK1/2, Akt, and NF-κB plays a central role in vincristine resistance in multiple myeloma cells. Leukemia Research 39(4): 445–452. https://doi.org/10.1016/j.leukres.2015.01.016
  • Wan D, Ouyang H (2018) Baicalin induces apoptosis in human osteosarcoma cell through ROS-mediated mitochondrial pathway. Natural product Research 32: 1996–2000. https://doi.org/10.1080/14786419.2017.1359173
  • Wang B, Huang T, Fang Q, Zhang X, Yuan J, Li M, Ge H (2020) Bone-protective and anti-tumor effect of baicalin in osteotropic breast cancer via induction of apoptosis. Breast Cancer Research and Treatment 184: 711–721. https://doi.org/10.1007/s10549-020-05904-y
  • Wang L, Li P, Feng K (2023) EGCG adjuvant chemotherapy: Current status and future perspectives. European Journal of Medicinal Chemistry 250: 115197. https://doi.org/10.1016/j.ejmech.2023.115197
  • Wang P, Heber D, Henning SM (2012) Quercetin increased the antiproliferative activity of green tea polyphenol (-)-epigallocatechin gallate in prostate cancer cells. Nutrition and Cancer 64: 580–587. https://doi.org/10.1080/01635581.2012.661514
  • Wang X-B, Wang S-S, Zhang Q-F, Liu M, Li H-L, Liu Y, Wang J-N, Zheng F, Guo L-Y, Xiang J-Z (2010) Inhibition of tetramethylpyrazine on P-gp, MRP2, MRP3 and MRP5 in multidrug resistant human hepatocellular carcinoma cells. Oncology Reports 23: 211–215. https://doi.org/10.3892/or_00000625
  • Wang X-F, Zhou Q-M, Du J, Zhang H, Lu Y-Y, Su S-B (2013) Baicalin suppresses migration, invasion and metastasis of breast cancer via p38MAPK signaling pathway. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents) 13: 923–931. https://doi.org/10.2174/18715206113139990143
  • Wang X, Hao M-W, Dong K, Lin F, Ren J-H, Zhang H-Z (2009) Apoptosis induction effects of EGCG in laryngeal squamous cell carcinoma cells through telomerase repression. Archives of Pharmacal Research 32: 1263–1269. https://doi.org/10.1007/s12272-009-1912-8
  • Wang Y-Q, Lu J-L, Liang Y-R, Li Q-S (2018a) Suppressive effects of EGCG on cervical cancer. Molecules 23: 2334. https://doi.org/10.3390/molecules23092334
  • Wang Y, Jia Y, Yang X, Liang B, Gao H, Yang T (2018b) A potential role of Baicalin to inhibit apoptosis and protect against acute liver and kidney injury in rat preeclampsia model. Biomedicine & Pharmacotherapy 108: 1546–1552. https://doi.org/10.1016/j.biopha.2018.09.107
  • Wei DZ, Yang JY, Liu JW, Tong WY (2003) Inhibition of liver cancer cell proliferation and migration by a combination of (-)-epigallocatechin-3-gallate and ascorbic acid. Journal of Chemotherapy 15: 591–595. https://doi.org/10.1179/joc.2003.15.6.591
  • Wong M-Y, Chiu GNC (2010) Simultaneous liposomal delivery of quercetin and vincristine for enhanced estrogen-receptor-negative breast cancer treatment. Anti-Cancer Drugs 21: 401–410. https://doi.org/10.1097/CAD.0b013e328336e940
  • Xu Z, Mei J, Tan Y (2017) Baicalin attenuates DDP (cisplatin) resistance in lung cancer by downregulating MARK2 and p-Akt. International Journal of Oncology 50: 93–100. https://doi.org/10.3892/ijo.2016.3768
  • Yang L, Zhang W, Chopra S, Kaur D, Wang H, Li M, Chen P, Zhang W (2020) The epigenetic modification of epigallocatechin gallate (EGCG) on cancer. Current Drug Targets 21: 1099–1104. https://doi.org/10.2174/1389450121666200504080112
  • Yin Z, Chen E, Cai X, Gong E, Li Y, Xu C, Ye Z, Cao Z, Pan J (2022) Baicalin attenuates XRCC1-mediated DNA repair to enhance the sensitivity of lung cancer cells to cisplatin. Journal of Receptors and Signal Transduction 42: 215–224. https://doi.org/10.1080/10799893.2021.1892132
  • Yu Y, Pei M, Li L (2015) Baicalin induces apoptosis in hepatic cancer cells in vitro and suppresses tumor growth in vivo. International Journal of Clinical and Experimental Medicine 8: 8958.
  • Zan L, Chen Q, Zhang L, Li XJB (2019) Epigallocatechin gallate (EGCG) suppresses growth and tumorigenicity in breast cancer cells by downregulation of miR-25. Bioengineered 10: 374–382. https://doi.org/10.1080/21655979.2019.1657327
  • Zhang Y, Wang X, Han L, Zhou Y, Sun SJB (2015) Green tea polyphenol EGCG reverse cisplatin resistance of A549/DDP cell line through candidate genes demethylation. Biomedicine 69: 285–290. https://doi.org/10.1016/j.biopha.2014.12.016
  • Zhao K, Wang Z, Li X, Liu J-l, Tian L, Chen J-qJM, Biochemistry C (2019) Exosome-mediated transfer of CLIC1 contributes to the vincristine-resistance in gastric cancer. Molecular and Cellular Biochemistry 462: 97–105. https://doi.org/10.1007/s11010-019-03613-9
  • Zhou D-H, Wang X, Yang M, Shi X, Huang W, Feng Q (2013) Combination of low concentration of (–)-epigallocatechin gallate (EGCG) and curcumin strongly suppresses the growth of non-small cell lung cancer in vitro and in vivo through causing cell cycle arrest. International Journal of Molecular Sciences 14: 12023–12036. https://doi.org/10.3390/ijms140612023
  • Zhou T, Zhang A, Kuang G, Gong X, Jiang R, Lin D, Li J, Li H, Zhang X, Wan J (2017) Baicalin inhibits the metastasis of highly aggressive breast cancer cells by reversing epithelial-to-mesenchymal transition by targeting β-catenin signaling. Oncology Reports 38: 3599–3607. https://doi.org/10.3892/or.2017.6011