A PRAGMATIC APPROACH TO TREAT LUNG CANCER THROUGH LOADING THEAFLAVIN -3,3’-DIGALLATE AND EPIGALLOCATECHIN GALLATE IN SPANLASTIC

Authors

  • SYED SAIF IMAM Department of Pharmaceutical Sciences, HIMT College of Pharmacy, Greater Noida, Uttar Pradesh, India.
  • SMRITI AGARWAL Department of Pharmaceutical Sciences, HIMT College of Pharmacy, Greater Noida, Uttar Pradesh, India.

DOI:

https://doi.org/10.22159/ajpcr.2021.v14i11.42757

Keywords:

Epigallocatechin gallate, Theaflavin -3,3’-digallate, Nano-particles, Spanlastic, Lung cancer

Abstract

Lung cancer has the highest mortality rate as compared to other cancers. The anti-proliferative and antioxidant potential of epigallocatechin gallate (EGCG) and Theaflavin -3,3’-digallate (TF3) can play a major role in treatment if delivered efficiently. To improve the chemical stability and medicinal potential of EGCG and TF3 in the respiratory tract, a spanlastic is developed which is composed of Tween-80, Span-60, and cholesterol which encapsulate EGCG and TF3 inside its vesicular structure and deliver it specifically to the target cancer cells. The cholesterol layer will produce efficient penetration while tween-80 and span-60 will help in easily deformability and lowers the interfacial tension hence, produces a small Z-average diameter which facilitates efficient penetration between layers of cells. The nano-vesicular structure ensures the APIs stability at alkaline pH (7.6) and also increases cellular antioxidant activity and Ferric reducing antioxidant powers values of APIs. Better encapsulation efficiency and safe consideration by MTT assay are major advantages of Spanlastic. The lung cancer cell loses the ability of apoptosis, which can revived with the help of a nano-vesicular system of EGCG and TF3 and in addition, there will be activation of several other properties such as cell arrest, activation of miR-210, suppression of cyclin D1, inhibition of MAPK, ERK, and JAK-STAT at their maximum potential. Furthermore, a special type of spacer and pMDI canister are developed in order to maximize the drug stability and efficiency of its delivery.

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References

Goodarzi E, Sohrabivafa M, Adineh HA, Moayed L, Khazaei Z. Geographical distribution global incidence and mortality of lung cancer and its relationship with the Human Development Index (HDI); An ecology study in 2018. World Cancer Res J 2019;6:e1354.

Kang SM, Sung HJ, Ahn JM, Park JY, Lee SY, Park CS, et al.. The haptoglobin β chain as a supportive biomarker for human lung cancers. Mol Biosyst 2011;7:1167-75. DOI: https://doi.org/10.1039/c0mb00242a

Minna JD, Roth JA, Gazdar AF. Focus on lung cancer. Cancer Cell 2002;1:49-52. DOI: https://doi.org/10.1016/S1535-6108(02)00027-2

Gadgeel SM, Kalemkerian GP. Racial differences in lung cancer. Cancer Metastasis Rev 2003;22:39-46. DOI: https://doi.org/10.1023/A:1022207917249

Randhawa MA, Alghamdi MS. Anticancer activity of Nigella sativa (black seed)-a review. Am J Chin Med 2011;39:1075-91. DOI: https://doi.org/10.1142/S0192415X1100941X

Fujiki H, Suganuma M. Green tea: An effective synergist with anticancer drugs for tertiary cancer prevention. Cancer Lett 2012;324:119-25. DOI: https://doi.org/10.1016/j.canlet.2012.05.012

Rong L, Ling C, Wallace Y, Peter AW, Fang Z. Niosomes consisting of tween-60 and cholesterol improve the chemical stability and antioxidant activity of (−)-epigallocatechin gallate under intestinal tract conditions. J Agric Food Chem 2016;64:9180-8. DOI: https://doi.org/10.1021/acs.jafc.6b04147

Cabrera C, Artacho R, Giménez R. Beneficial effects of green tea--a review. J Am Coll Nutr 2006;25:79-99. DOI: https://doi.org/10.1080/07315724.2006.10719518

Zhang J, Nie S, Wang S. Nanoencapsulation enhances epigallocatechin- 3-gallate stability and its antiatherogenic bioactivities in macrophages. J Agric Food Chem 2013;61:9200-9. DOI: https://doi.org/10.1021/jf4023004

Viktoria K, Raul ZR, Leila LB, Isabelle R, Augustin S, Nadia S, et al.. Intake estimation of total and individual flavan-3-ols, proanthocyanidins and theaflavins, their food sources and determinants in the European prospective investigation into cancer and nutrition. Br J Nutr 2012;108:1095-108. DOI: https://doi.org/10.1017/S0007114511006386

Lai KL, Yalun S, Ruoyun C, Zesheng Z, Yu H, Zhen YC. Theaflavins in black tea and catechins in green tea are equally effective antioxidants. J Nutr 2001;131:2248-51. DOI: https://doi.org/10.1093/jn/131.9.2248

Ru QM, Yu HL, Huang QR. Encapsulation of epigallocatechin-3- gallate (EGCG) using oil-in-water (O/W) submicrometer emulsions stabilized by iota-carrageenan and beta lactoglobulin. J Agric Food Chem 2010;58:10373-81. DOI: https://doi.org/10.1021/jf101798m

Jhoo JW, Lo CY, Li S, Sang S, Ang CY, Heinze TM, et al.. Stability of black tea polyphenol, theaflavin, and identification of theanaphthoquinone as its major radical reaction product. J Agric Food Chem 2005;53:6146-50. DOI: https://doi.org/10.1021/jf050662d

Sharma A, Pahwa S, Bhati S, Kudeshia P. Spanlastics: A modern approach for nanovesicular drug delivery system. IJPSR 2020;11:1057-65.

Badria F, Mazyed E. Formulation of nanospanlastics as a promising approach for improving the topical delivery of a natural leukotriene inhibitor (3- acetyl-11-keto-β-boswellic Acid): Statistical optimization, in vitro characterization, and ex vivo permeation study. Drug Des Dev Ther 2020;14:3697-721. DOI: https://doi.org/10.2147/DDDT.S265167

Federico L, Giovanni F. Targeting drugs to the airways: The role of spacer devices Exp Opin Drug Deliv 2009;6:91-102. DOI: https://doi.org/10.1517/17425240802637862

Dale GN, Daneel F, Yu-Dong Z. Epigallocatechin-3-gallate (EGCG): Chemical and biomedical perspectives. Phytochemistry 2006;67:1849-55. DOI: https://doi.org/10.1016/j.phytochem.2006.06.020

Pons-Fuster LE, Gómez GF, López JP. Combination of 5-florouracil and polyphenol EGCG exerts suppressive effects on oral cancer cells exposed to radiation. Arch Oral Biol 2019;101:8-12. DOI: https://doi.org/10.1016/j.archoralbio.2019.02.018

Thakur VS, Gupta K, Gupta S. Green tea polyphenols cause cell cycle arrest and apoptosis in prostate cancer cells by suppressing class I histone deacetylases. Carcinogenesis 2012;33:377-84. DOI: https://doi.org/10.1093/carcin/bgr277

Lu G, Liao J, Yang G, Reuhl KR, Hao X, Yang CS. Inhibition of adenoma progression to adenocarcinoma in a 4-(methylnitrosamino)-1- (3-pyridyl)-1-butanone-induced lung tumorigenesis model in A/J mice by tea polyphenols and caffeine. Cancer Res 2006;66:11494-501. DOI: https://doi.org/10.1158/0008-5472.CAN-06-1497

Larsen CA, Bisson WH, Dashwood RH. Tea catechins inhibit hepatocyte growth factor receptor (MET kinase) activity in human colon cancer cells: Kinetic and molecular docking studies. J Med Chem 2009;52:6543-5. DOI: https://doi.org/10.1021/jm901330e

Belguise K, Guo S, Sonenshein GE. Activation of FOXO3a by the green tea polyphenol epigallocatechin-3-gallate induces estrogen receptor alpha expression reversing invasive phenotype of breast cancer cells. Cancer Res 2007;67:5763-70. DOI: https://doi.org/10.1158/0008-5472.CAN-06-4327

Neha AS, Abdul KA, Zaved AK. Potential neuroprotective properties of epigallocatechin-3-gallate (EGCG). Nutr J 2016;15:60. DOI: https://doi.org/10.1186/s12937-016-0179-4

Sunil KR, Balenahalli NR, Bruno V. Neuro-nutrients as anti- Alzheimer’s disease agents: A critical review. Crit Rev Food Sci Nutr 2019;59:2999-3018. DOI: https://doi.org/10.1080/10408398.2018.1481012

Qiu YF, Qing SL, Xiao ML, Ru YQ, Rui Y, Xu ML, et al.. Antidiabetic effects of tea. Molecules 2017;22:849. DOI: https://doi.org/10.3390/molecules22050849

Steinmann J, Buer J, Pietschmann T, Steinmann E. Anti-infective properties of epigallocatechin-3-gallate (EGCG), a component of green tea. Br J Pharmacol 2013;168:1059-73. DOI: https://doi.org/10.1111/bph.12009

Geleijnse JM, Launer LJ, Hofman A, Pols HA, Witteman JC. Tea flavonoids may protect against atherosclerosis: The Rotterdam study. Arch Intern Med 1999;159:2170-4. DOI: https://doi.org/10.1001/archinte.159.18.2170

Khurana S, Venkataraman K, Hollingsworth A, Piche M, Tai TC. Polyphenols: Benefits to the cardiovascular system in health and in aging. Nutrients 2013;5:3779-827. DOI: https://doi.org/10.3390/nu5103779

Ángela VC, Nereida JO, Miguel AM, Emilia GM, Juan CS. Antiviral properties of the natural polyphenols delphinidin and epigallocatechin gallate against the flaviviruses west nile virus, zika virus, and dengue virus. Front Microbiol 2017;8:1314. DOI: https://doi.org/10.3389/fmicb.2017.01314

Yokozawa T, Nakagawa T, Kitani K. Antioxidative activity of green tea polyphenol in cholesterol-fed rats. J Agric Food Chem 2002;50:3549-52. DOI: https://doi.org/10.1021/jf020029h

Kuriyama S, Shimazu T, Ohmori K, Kikuchi N, Nakaya N, Nishino Y, et al.. Green tea consumption and mortality due to cardiovascular disease, cancer, and all causes in Japan: The Ohsaki study. JAMA 2006;296:1255-65. DOI: https://doi.org/10.1001/jama.296.10.1255

Granja A, Pinheiro M, Reis S. Epigallocatechin gallate nanodelivery systems for cancer therapy. Nutrients 2016;8:307. DOI: https://doi.org/10.3390/nu8050307

Diepvens K, Kovacs EM, Vogels N, Westerterp-Plantenga MS. Metabolic effects of green tea and of phases of weight loss. Physiol Behav 2006;87:185-91. DOI: https://doi.org/10.1016/j.physbeh.2005.09.013

Intra J, Kuo SM. Physiological levels of tea catechins increase cellular lipid antioxidant activity of Vitamin C and Vitamin E in human intestinal caco-2 cells. Chem Biol Interact 2007;169:91-9. DOI: https://doi.org/10.1016/j.cbi.2007.05.007

Yamada S, Tsukamoto S, Huang Y, Makio A, Kumazoe M, Yamashita S, et al.. Epigallocatechin-3-O-gallate up-regulates microRNA-let- 7b expression by activating 67-kDa laminin receptor signaling in melanoma cells. Sci Rep 2016;6:19225. DOI: https://doi.org/10.1038/srep19225

Milligan SA, Burke P, Coleman DT, Bigelow RL, Steffan JJ, Carroll JL, et al.. The green tea polyphenol EGCG potentiates the antiproliferative activity of c-Met and epidermal growth factor receptor inhibitors in non-small cell lung cancer cells. Clin Cancer Res 2009;15:4885-94. DOI: https://doi.org/10.1158/1078-0432.CCR-09-0109

Zhang X, Min KW, Wimalasena J, Baek SJ. Cyclin D1 degradation and p21 induction contribute to growth inhibition of colorectal cancer cells induced by epigallocatechin-3-gallate. J Cancer Res Clin Oncol 2012;138:2051-60. DOI: https://doi.org/10.1007/s00432-012-1276-1

Satoh M, Takemura Y, Hamada H, Sekido Y, Kubota S. EGCG induces human mesothelioma cell death by inducing reactive oxygen species and autophagy. Cancer Cell Int 2013;13:19. DOI: https://doi.org/10.1186/1475-2867-13-19

Li W, Saud SM, Young MR, Chen G, Hua B. Targeting AMPK for cancer prevention and treatment. Oncotarget 2015;6:7365-78. DOI: https://doi.org/10.18632/oncotarget.3629

Bing-Huei C, Chia-Hung H, Su-Yun T, Chian-Yu W, Chi-Chung W. Anticancer effects of epigallocatechin-3-gallate nanoemulsion on lung cancer cells through the activation of AMP-activated protein kinase signaling pathway. Sci Rep 2020;10:5163. DOI: https://doi.org/10.1038/s41598-020-62136-2

Zhang L, Xie J, Gan R, Wu Z, Luo H, Chen X, et al.. Synergistic inhibition of lung cancer cells by EGCG and NF-κB inhibitor BAY11-7082. J Cancer 2019;10:6543-56. DOI: https://doi.org/10.7150/jca.34285

He HF. Research progress on theaflavins: Efficacy, formation, and preparation. Food Nutr Res 2017;61:1344521. DOI: https://doi.org/10.1080/16546628.2017.1344521

de Oliveira A, Prince D, Lo CY, Lee LH, Chu TC. Antiviral activity of theaflavindigallate against herpes simplex virus Type 1. Antiviral Res 2015;118:56-67. DOI: https://doi.org/10.1016/j.antiviral.2015.03.009

Betts JW, Kelly SM, Haswell SJ. Antibacterial effects of theaflavin and synergy with epicatechin against clinical isolates of Acinetobacter baumannii and Stenotrophomonas maltophilia. Int J Antimicrob Agents 2011;38:421-5. DOI: https://doi.org/10.1016/j.ijantimicag.2011.07.006

Yuanqing H, Li L. Anti-aging and anti-osteoporosis effects of green teen polyphenol in a premature aging model of Bmi-1 knockout mice. Int J Clin Exp Pathol 2017;10:3765-77.

O’Neill EJ, Termini D, Albano A, Tsiani E. Anti-cancer properties of theaflavins. Molecules 2021;26:987. DOI: https://doi.org/10.3390/molecules26040987

Zeng J, Deng Z, Zou Y, Liu C, Fu H, Gu Y, et al.. Theaflavin alleviates oxidative injury and atherosclerosis progress via activating microRNA- 24-mediated Nrf2/HO-1 signal. Phytother Res 2021;35:3418-27. DOI: https://doi.org/10.1002/ptr.7064

Aneja R, Odoms K, Denenberg AG, Wong HR. Theaflavin, a black tea extract, is a novel anti-inflammatory compound. Crit Care Med 2004;32:2097-103. DOI: https://doi.org/10.1097/01.CCM.0000142661.73633.15

Duiyan J, Yi X, Xin M, Qing M, Ying G, Bo L, et al.. Antiobesity and lipid lowering effects of theaflavins on high-fat diet induced obese rats. J Funct Foods 2013;5:1142-50. DOI: https://doi.org/10.1016/j.jff.2013.03.011

Lombardo Bedran TB, Morin MP, Palomari Spolidorio D, Grenier D. Black tea extract and its theaflavin derivatives inhibit the growth of periodontopathogens and modulate interleukin-8 and β-defensin secretion in oral epithelial cells. PLoS One 2015;10:e0143158. DOI: https://doi.org/10.1371/journal.pone.0143158

Koch W. Theaflavins, thearubigins, and theasinensins. In: Xiao J, Sarker S, Asakawa Y, editors. Handbook of Dietary Phytochemicals. Germany: Springer; 2019. DOI: https://doi.org/10.1007/978-981-13-1745-3_20-1

Wu YY, Li W, Xu Y, Jin EH, Tu YY. Evaluation of the antioxidant effects of four main theaflavin derivatives through chemiluminescence and DNA damage analyses. J Zhejiang Univ Sci B 2011;12:744-51. DOI: https://doi.org/10.1631/jzus.B1100041

Ali I, Masood SB, Hang X, Muhammad I, Abdur R, Mohammad SM, et al.. Inhibitory effect of black tea (Camellia sinensis) theaflavins and thearubigins against HCT 116 colon cancer cells and HT 460 lung cancer cells. J Food Biochem 2019;43:e12822. DOI: https://doi.org/10.1111/jfbc.12822

Guang YY, Zhi YW, Sungbin K, Jie L, Darren NS, Xiaoxin C, et al.. Characterization of early pulmonary hyperproliferation and tumor progression and their inhibition by black tea in a 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone-induced Lung tumorigenesis model with a/j mice. Cancer Res 1997;57:05022. DOI: https://doi.org/10.1093/carcin/18.12.2361

Park SK, Dahmer MK, Quasney MW. MAPK and JAK-STAT signaling pathways are involved in the oxidative stress-induced decrease in expression of surfactant protein genes. Cell Physiol Biochem 2012;30:334-46. DOI: https://doi.org/10.1159/000339068

Singh BN, Harikesh BS, Singh A, Alim HN, Braj RS. Dietary phytochemicals alter epigenetic events and signaling pathways for inhibition of metastasis cascade. Cancer Metastasis Rev 2014;33:41-85. DOI: https://doi.org/10.1007/s10555-013-9457-1

Shalini S, Dorstyn L, Dawar S, Kumar S. Old, new and emerging functions of caspases. Cell Death Differ 2015;22:526-39. DOI: https://doi.org/10.1038/cdd.2014.216

Shao J, Meng Q, Li Y. Theaflavins suppress tumor growth and metastasis via the blockage of the STAT3 pathway in hepatocellular carcinoma. Onco Targets Ther 2016;9:4265-75. DOI: https://doi.org/10.2147/OTT.S102858

Hassan LA, Omer H, Yi WY, Petra B. Lung cancer: Biology and treatment options. Biochim Biophys Acta 2015;1856:189-210. DOI: https://doi.org/10.1016/j.bbcan.2015.08.002

Kumar V, Abbas AK, Fausto N, Robbins SL, Cotran RS. Robbins and Cotran Pathologic Basis of Disease. Philadelphia, PA: Elsevier, Saunders; 2020. p. 205.

Gandara DR, Hammerman PS, Sos ML, Lara PN Jr., Hirsch FR. Squamous cell lung cancer: From tumor genomics to cancer therapeutics. Clin Cancer Res 2015;21:2236-43. DOI: https://doi.org/10.1158/1078-0432.CCR-14-3039

Johnson BE, Crawford J, Downey RJ, Ettinger DS, Fossella F, Grecula JC, et al., National Comprehensive Cancer Network (NCCN). Small cell lung cancer clinical practice guidelines in oncology. J Natl Compr Canc Netw 2006;4:602-22. DOI: https://doi.org/10.6004/jnccn.2006.0050

Rajdev K, Siddiqui AH, Ibrahim U, Patibandla P, Khan T, El-Sayegh D. An unusually aggressive large cell carcinoma of the lung: Undiagnosed until autopsy. Cureus 2018;10:e2202. DOI: https://doi.org/10.7759/cureus.2202

Tochigi N, Dacic S, Nikiforova M, Cieply KM, Yousem SA. Adenosquamous carcinoma of the lung: A microdissection study of KRAS and EGFR mutational and amplification status in a western patient population. Am J Clin Pathol 2011;135:783-9. DOI: https://doi.org/10.1309/AJCP08IQZAOGYLFL

Wu R. Large cell neuroendocrine carcinoma. Pathology Outlines. Avaialble from: https://www.pathologyoutlines.com/topic/ lungtumorlargecellNE.html. [Last accessed on 2021 Sep 11].

Macarenco RS, Uphoff TS, Gilmer HF, Jenkins RB, Thibodeau SN, Lewis JE, et al.. Salivary gland-type lung carcinomas: An EGFR immunohistochemical, molecular genetic, and mutational analysis study. Mod Pathol 2008;21:1168-75. DOI: https://doi.org/10.1038/modpathol.2008.113

Aroor AR, Prakasha SR, Seshadri S, Raghuraj U. A study of clinical characteristics of mediastinal mass. J Clin Diagn Res 2014;8:77-80. DOI: https://doi.org/10.7860/JCDR/2014/7622.4013

Lee MJ, Maliakal P, Chen L, Meng X, Bondoc FY, Prabhu S, et al.. Pharmacokinetics of tea catechins after ingestion of green tea and (-)-epigallocatechin-3-gallate by humans: Formation of different metabolites and individual variability. Cancer Epidemiol Biomarkers Prev 2002;11:1025-32.

Maity S, Ukil A, Vedasiromoni JR, Das PK. Biodistribution and pharmacokinetics of theaflavin-3,3’-digallate, the major antioxidant of black tea, in mice. Int J Pharmacol 2006;2:240-6. DOI: https://doi.org/10.3923/ijp.2006.240.246

Kakkar S, Kaur IP. Spanlastics--a novel nanovesicular carrier system for ocular delivery. Int J Pharm 2011;413:202-10. DOI: https://doi.org/10.1016/j.ijpharm.2011.04.027

Chen L, Lee MJ, Li H, Yang CS. Absorption, distribution, elimination of tea polyphenols in rats. Drug Metab Dispos 1997;25:1045-50.

Rashid S. Comparative pharmacokinetic study of theaflavin in healthy and experimentally induced liver damage rabbits. Iraqi J Vet Sci 2019;33:235-42. DOI: https://doi.org/10.33899/ijvs.2019.162962

Vondra V, Sladek K, Kotasová J, Terl M, Rossetti A, Cantini L. A new HFA-134a propellant in the administration of inhaled BDP via the Jet spacer: Controlled clinical trial vs the conventional CFC. Respir Med 2002;96:784-9. DOI: https://doi.org/10.1053/rmed.2002.1348

Takemoto M, Takemoto H. Synthesis of theaflavins and their functions. Molecules 2018;23:918.JA DOI: https://doi.org/10.3390/molecules23040918

Published

07-11-2021

How to Cite

IMAM, S. S., and S. AGARWAL. “A PRAGMATIC APPROACH TO TREAT LUNG CANCER THROUGH LOADING THEAFLAVIN -3,3’-DIGALLATE AND EPIGALLOCATECHIN GALLATE IN SPANLASTIC”. Asian Journal of Pharmaceutical and Clinical Research, vol. 14, no. 11, Nov. 2021, pp. 1-8, doi:10.22159/ajpcr.2021.v14i11.42757.

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Review Article(s)