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Antitumor effects of octyl gallate on hypopharyngeal carcinoma cells

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Introduction Introduction

Oral cancer accounts for approximately 8% of all malignancy which ranges from the 6th to the 9th most popular cancer all over the world [1]. About 90% of oral cancer is squamous cell carcinoma (OSCC) developed in the mucosal membranes of mouth, tongue, floors of mouths, gums, and hard palates [2,3]. High-risk factors of OSCC include tobacco or/and alcohol consumption, micronutrient inadequacy, human papillomavi- rus infection and ultra-violet radiation exposure. Despite the therapeutic advances, the relapse incidence of OSCC is still 40 to 60% and the survival rate for longer than three years is only 30 to 50% after treatment [1,4].

Octyl gallate (OG) and other members of gallate family have been well-known for various biological activities such as He- licobacter pylori inhibition, neurodegeneration improvement

and tumorigenesis suppression [5]. Gallic acid and its ester derivatives were reported to have various therapeutic effects in anti-oxidation, anti-inflammation and anti-tumorigenesis [6,7]. Particularly, OG showed characteristic anticancer ef- fects on various types of cancers with various molecular mechanisms. In human breast cancer cell lines of MCF-7 and MDA-MB-231, OG and gallic acid, isolated from Terminalia bellarica, inhibited cell cycle progression and induced apopto- sis by downregulating positive cell cycle regulators of Cyclins and Cdks and upregulating negative regulators such as p21 and p27 [8]. In murine melanoma cell line, OG promoted oxi- dative stress and mitochondrial dysfunction to increase pro- apoptotic protein Bax while decreasing antiapoptotic protein Bcl-2, leading to caspase 3 activation and cell death [9]. From this perspective, we were motivated to investigate the OG’s effects on OSCC and its underlying molecular mechanism. In Int J Oral Biol 45:218-224, 2020

pISSN: 1226-7155 • eISSN: 2287-6618 https://doi.org/10.11620/IJOB.2020.45.4.218

Antitumor effects of octyl gallate on hypopharyngeal carcinoma cells

Trang NTK and Hoon Yoo*

Department of Pharmacology and Dental Therapeutics, College of Dentistry, Chosun University, Gwangju 61452, Republic of Korea

The antitumor effects of octyl gallate (OG) were investigated on FaDu human hypopharyngeal squamous carcinoma cells. At various concentrations, OG inhibited the proliferation of FaDu cells by suppressing cell cycle regulators and induced apoptosis by activating caspase 3 and its downstream poly (ADP-ribose) polymerase, thereby damaging DNA. Immunoblotting demonstrated that OG significantly suppressed the expression of integrin family proteins (integrin α4, αv, β3, β4), hindering cell adhesion. The reduced expression of integrins subsequently mediated the mitogen- activated protein kinase signaling pathway to stimulate the activation of extracellular signal-regulated kinases and c-jun N-terminal kinases, leading to apoptosis. Thus, OG demonstrated antitumor activity on hypopharyngeal squamous carcinoma cells by suppressing cell proliferation and inducing apoptosis.

Keywords: Pharyngeal squamous cell carcinoma, Octyl gallate, Apoptosis, Mitogen-activated protein kinase signaling pathway, Integrins

Received August 15, 2020; Revised December 15, 2020; Accepted December 16, 2020

*Correspondence to: Hoon Yoo, E-mail: hoon_yoo@chosun.ac.kr. https://orcid.org/0000-0002-9249-1446 Copyright © The Korean Academy of Oral Biology

CC

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by- nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Original Article IJOB

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the present study, we demonstrated the effects of OG on cell proliferation and apoptosis induction in FaDu pharyngeal squa- mous carcinoma cells. OG significantly inhibited the cell prolif- eration by decreasing cell cycle proteins and induced caspase- dependent apoptosis by the inhibition of the integrin family proteins and the activation of downstream mitogen-activated protein kinase (MAPK) pathway (extracellular signal-regulated kinases [ERK] and c-jun N-terminal kinases [JNK]).

Materials and Methods Materials and Methods

1. Materials and reagents

Thiazolyl blue tetrazolium bromide (MTT), dimethylsulfoxide (DMSO), and OG were purchased from Sigma-Aldrich (St.

Louis, MO, USA). Minimum essential medium (MEM), fetal bovine serum (FBS), trypsin-ethylenediaminetetraacetic acid (EDTA), and antibiotic-antimycotic solution were from Welgene (Daegu, Korea). The antibodies of Cyclin A, Cyclin B1, Cdk2, Cdk4 and precursor caspase 3 were from Santa Cruz Biotech- nology (Santa Cruz, CA, USA) and cleaved poly (ADP-ribose) polymerase (PARP) was obtained from Abcam (Seoul, Korea).

Primary antibodies of integrin family (integrin α4, αv, β3, β4), Cleaved caspase 3, p-p42/p44 ERK1/2, p-p38 MAPK1/2, p- JNK, g-H2AX were purchased from Cell Signaling (Danvers, MA, USA).

2. Cell culture

FaDu hypopharyngeal squamous cancer cells (Korean cell line bank) were grown in MEM media supplemented with 10%

FBS and 100 units/mL penicillin/streptomycin and incubated in a humidified atmosphere (37℃ with 5% CO 2 ). For experiments, cells (2 × 10 5 cells/mL) were seeded in MEM and incubated overnight to reach about 70 to 80% of confluency before treat- ing with OG.

3. Cell viability assay

The cell viability was measured by an MTT assay. Briefly, cells (4 × 10 4 cells/well) were seeded in 96-well plate for 24 hours. In 80% of confluence, cells were treated with various doses of OG. After the period of 24 or 48 hours, the media were replaced by MTT (0.5 mg/mL) solution and the plates were further incubated for 4 hours until violet crystals (forma- zan) were formed. MTT solution was aspirated and 200 µL of

DMSO was added to dissolve formazan. The absorbance at 570 nm was measured by using Multiskan TM FC Microplate Photometer (Thermo Fisher Scientific, Waltham, MA, USA).

4. Western blotting

After treated with different concentrations of OG for 24 hours, proteins were collected by using lysis buffer (20 mM Tris-HCl pH 7.5, 150 mM NaCl, 1 mM disodium ethylenedi- aminetetraacetic acid [Na 2 EDTA], 1 mM ethylene glycol tet- raacetic acid, 1% Triton, 2.5 mM sodium pyrophosphate, 1 mM β-glycerophosphate, 1 mM Na 3 VO 4 , 1 µg/mL leupeptin, 1 mM phenylmethylsulfonyl fluoride [PMSF] and 1% phosphatase in- hibitor cocktail) (Sigma-Aldrich). Total proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), transferred onto polyvinylidene fluoride mem- branes by using a Biorad wet blot system. The membrane was blocked by 5% skim milk for 1 hour at 4℃ and then incubated with primary antibody overnight at 4℃. Excessive antibody was removed by washing buffer (phosphate buffer saline [PBS]

with 1% tween-20). Thereafter, the membrane was incubated with corresponding horseradish peroxidase (HPR)-conjugated secondary antibodies for 2 to 3 hours at room temperature.

Finally, target proteins were detected by chemo-luminescence reagents and captured by Kodak Digital Science Image Station (Bruker BioSpin, Billerica, MA, USA). Quantification analysis was performed by using Carestream molecular imaging soft- ware (Carestream Health Inc., Rochester, NY, USA).

5. Immunofluorescence imaging

FaDu cells (1 × 10 5 cells/well) were seeded on coverslips in 24-well plates for 24 hours. After reaching 90% confluence, cells were treated with various concentrations of OG for 24 hours or 48 hours. After washed with PBS, cells were fixed with 4%

paraformaldehyde (PFA) for 15 minutes at room temperature.

Residual PFA was removed by washing with PBS (3×). Washing

buffer (PBS with 1% goat serum and 0.1% Triton X-100) was

used to block and permeabilize cell membranes in 30 minutes

at 4℃. Thereafter, cells were treated with primary antibody at

4℃ overnight and then followed by secondary antibodies and

4,6-diamidino-2-phenylindole (DAPI) for 2 hours at room tem-

perature. Finally, coverslips were mounted and images were

captured by fluorescence microscopy (Carl Zeiss, Oberkochen,

Germany).

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6. Statistical analysis

All experiments were triplicated and the data were shown as the mean ± standard errors. The Student’s t-test was used to analyze statistical significance between two groups.

Results Results

1. Octyl gallate inhibited FaDu cell proliferation

To investigate the cell viability on FaDu cells, various con- centrations of OG (0 to 200 µM) were treated with cells for 24 or 48 hours, and then an MTT assay was carried to identify the percent cell viability. OG inhibited the proliferation of FaDu cells in time and dose-dependent manners with half-maximal inhibitory concentration (IC50) of 121.1 µM at 24 hours and the cell viability was rapidly decreased when cells were exposed to OG longer (48 hours) (Fig. 1).

2. OG’s effect on cell cycle regulators

The expression of Cyclin B and Cdk2 were significantly sup- pressed in a dose-dependent manner while Cyclin A and Cdk4 were less affected in the OG range of 50 to 100 µM. At 150 µM of OG, Cyclin A and Cdk4 were also suppressed (Fig. 2).

3. OG induced caspase-dependent apoptosis

In Western blotting, OG significantly induced the cleavage of endoprotease caspase 3 and PARP. The appearance of ex- ecutioner caspase 3 and its downstream PARP bands in the cleaved form demonstrated that OG-induced apoptosis was

0 120 100 80 60 40 20

Cell viability (%)

OG ( M)  0

25 50 100 200

24 hr 48 hr

*

*

*

*

* *

*

Fig. 1. Cell viability of octyl gallate (OG) on FaDu cells. Cells were treated with OG from 0 to 200 µM. After a period of 24 hours or 48 hours, the percent cell viability was measured by an MTT assay as described in the methods. Vertical bars indicate the mean ± standard errors obtained from three independent experiments.

*p < 0.05 versus control group.

Cyclin A 120

100 80 60 40 20

Percent protein (%)

0

Cyclin B1 Cdk2 Cdk4

0 50 100 150

*

*

*

*

* Cyclin A

Cyclin B

Cdk2

Cdk4

Beta actin OG ( M) 

0 50 100 150

A B

Fig. 2. The octyl gallate (OG) effects on cell cycle regulators. Cells were treated with various concentrations of OG from 0 to 150 µM for 24 hours. (A) West- ern blotting was carried out to detect the expression of cell cycle proteins. (B) The intensity of protein band was normalized with beta actin and graphed by using Sigma-Plot 12.0 (Systat Software, San Jose, CA, USA). Vertical bars indicate means and standard errors (n = 3).

*p < 0.05 versus control group.

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occurred through the caspase-dependent pathway (Fig. 3).

4. OG caused DNA damage on FaDu cells

To examine the effect of OG on DNA damage, a typical marker of double-strand DNA breaks (p-H2AX or g-H2AX) was used in western blotting and immunofluorescence imaging.

Under OG treatment, p-H2AX expression in Western blotting was increased and reached the maximum level at 150 µM of OG treatment (Fig. 4). Similarly, strong expression of p-H2AX was appeared dose-dependently in the fluorescence image.

5. OG suppressed the expression of integrin family proteins

OG suppressed the expression of various types of integrins (both alpha and beta subunits) on Fadu cells. The detachment of cell clumps was also observed under the OG treatment (data not shown). In western blotting results, the expression of integrin α4 was rapidly reduced even at low dose of OG while integrin αv, β3, and β5 were gradually decreased (Fig. 5). On SDS-PAGE, integrin α4 migrated as three different molecular sizes (mature proteins of 180 and 150 kDa and a precursor form of 140 kDa). At a low concentration of OG (50 µM), the expression of integrin α4 of mature forms (150 and 180 kDa proteins) were significantly suppressed while the expression of a precursor form (140 kDa) was only slightly decreased (Fig. 5).

6. OG activated ERK and JNK in MAPK pathway Under various doses of OG treatment for 24 hours, the ex-

pressions of phosphorylated ERK1/2 and JNKs were increased while p38 remained unchanged. Furthermore, phosphorylated c-jun (p-c-jun), a downstream transcription factor of JNKs, was also highly expressed under the high concentration of OG (150 µM) (Fig. 6).

Discussion Discussion

In this study we investigated the antitumor effect of OG on FaDu cells by tracking the expression of essential proteins involved in cell proliferation and apoptosis. OG inhibited cell proliferation dose-dependently with IC50 of 121.1 µM in 24 hours treatment. Under this condition, protein expression for cell cycle regulation (cyclin A, cyclin B, Cdk2, and Cdk4) was significantly decreased, and DNA was damaged which was confirmed by the detection of the phosphorylated g-H2AX, a

Precusor caspase 3

Cleaved caspase 3

Cleaved PARP

Beta actin OG ( M) 

0 50 100 150

19 17

Fig. 3. Octyl gallate (OG) induced caspase-dependent apoptosis. The cells were treated with OG for 24 hours and total proteins were collected for west- ern blotting. The intensity of protein band was normalized with beta actin and graphed by using SigmaPlot 12.0 (Systat Software, San Jose, CA, USA).

PARP, poly (ADP-ribose) polymerase.

p-H2AX

Beta actin OG ( M) 

0 50 100 150

A

0

50

100

DAPI Tubulin p-H2AX Merge

B

Fig. 4. Octyl gallate (OG) caused DNA damage on FaDu cells. (A) Cells

were treated with various concentrations of OG for 24 hours, and then

proteins were detected by western blotting. (B) To visualize the expression

and subcellular location of p-H2AX, cells were seeded on coverslips before

treated with OG. Thereafter, coverslips were stained with 4,6-diamidino-

2-phenylindole (DAPI), p-H2AX, and tubulin antibodies prior to capture the

fluorescence images at 400× magnification.

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typical double-stranded DNA marker. FaDu cells exposed to OG showed shrunken morphology with low density in cell pop- ulation (data not shown). Presumably chromosomal damage might be due to the reactive oxygen species or other stress mediators generated by OG interaction with cellular organelles.

Thereby, cells delayed the cell-division to repair the dam- aged DNA by reducing the expression of cell cycle promoting proteins (Cyclins and Cdks). However, at high dose condition of OG (150 µM), cells were forced to suicide by activating the caspase cascade. Interestingly, the expression of integrins was downregulated dose-dependently in response to OG treat- ment although the degree of reduction was integrin subunit dependent. For example, integrin α4 and β5 were significantly downregulated under OG treatment while integrin αv and β3 were slightly inhibited. Particularly the expression of matured integrin α4 (150 kDa) was dramatically decreased even at low dose (50 µM) of OG treatment while the precursor form of integrin α4 (140 kDa) was decreased slightly only. Integrins, a family of transmembrane proteins, comprise of noncovalently associated α and β subunits and transmit signals inwards/

outwards through the cells to mediate cell adhesion, migration, cell proliferation, cell survival and even cell death via binding to extracellular matrix ligands such as collagen, fibronectin, laminin, or growth factors [10,11]. Integrin α4 was known to play significant roles in tumor development and metastasis and several integrin α4 antagonists were actually explored to develop the antitumor therapy [12,13]. In this context, the suppressed expression of integrin α4 and other integrin family (integrin αv, β3, β4) by OG treatment could be due to the an- tagonistic action of OG to integrins.

MAPK comprises three subgroups including c-jun N-ter-

Integrin 5  140

100 80 60 40 20

Percent protein (%)

0

0 50 100 150 Integrin 5 

Integrin 3 

Integrin v 

Integrin 4 

Beta actin OG ( M) 

0 50 100 150

A B

180

150 140

Integrin 3  Integrin v  Integrin 4

(150 kDa)  Integrin 4 (140 kDa) 

* * *

*

* 120

Fig. 5. Octyl gallate (OG) suppressed the expression of integrin family proteins. (A) FaDu cells were treated with OG for 24 hours. Antibodies of integrin α4, αv, β3, β5 were used to detect the integrin expression by western blotting. (B) The expression levels of integrins were measured using Kodak Molecular Imaging Software (Carestream Health, Inc., Rochester, NY, USA) and graphed by using SigmaPlot 12.0 (Systat Software, San Jose, CA, USA). Vertical bars indicate means and standard errors (n = 3).

*p < 0.05 versus control group.

p-ERK1/2

p-p38

p-JNK

p-c-jun

Beta actin OG ( M) 

0 50 100 150

44 42

54

46

Fig. 6. Octyl gallate (OG) activated extracellular signal-regulated kinases

(ERK) and c-jun N-terminal kinases (JNK) in mitogen-activated protein

kinase (MAPK) pathway. The expression of p-ERK1/2, p-p38, p-JNK, and

p-c-jun were detected by western blotting and the intensity of protein band

was normalized with beta actin.

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minal kinase 1/2 (JNK1/2), stress-activated protein kinases (p38) and extracellular signal-regulated kinase 1/2 (ERK1/2).

MAPK plays an essential role in maintaining cellular homeo- stasis and regulating cell proliferation and apoptosis as well [14,15]. MAPK may function as either anti-apoptotic or pro- apoptotic effector depending on the stimulus and the cell circumstances. Especially ERK1/2 was the most characterized subfamily which promotes cell survival or induces apoptosis in certain circumstances [15]. For example, DNA damaging stim- uli such as ionizing irradiation, ultraviolet irradiation, etoposide (an anti-cancer drug) activated the ERK1/2 pathway to induce apoptosis [16,17]. In our results, significant expression of p- ERK, p-JNK and its downstream transcription factor p-c-jun demonstrates that OG functioned as an exogenous stimulus to induce apoptosis on FaDu cells through the activation of ERK and JNK pathways. It is unclear whether there is any crosstalk between the OG-mediated inhibition of the integrin expression and the overexpression of p-ERK and p-JNK. The shortage

of integrin expression by OG treatment may have triggered the overexpression of other growth factors for compensation, leading to the activation of downstream regulators (p-ERK1/2 and p-JNK p-c-jun), and eventually inducing the cell death via caspase activation [18]. Overall, we demonstrated that OG has antitumor activity on hypopharyngeal squamous carcinoma cells by suppressing cell proliferation and inducing apoptosis.

Acknowledgements Acknowledgements

This study was supported by the research funds from Cho- sun University (2018).

Conflicts of Interest Conflicts of Interest

No potential conflict of interest relevant to this article was reported.

References References

1. Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Win- quist E, Gorbounova V, Tjulandin S, Shin DM, Cullen K, Ervin TJ, Murphy BA, Raez LE, Cohen RB, Spaulding M, Tishler RB, Roth B, Viroglio Rdel C, Venkatesan V, Romanov I, Agar- wala S, Harter KW, Dugan M, Cmelak A, Markoe AM, Read PW, Steinbrenner L, Colevas AD, Norris CM Jr, Haddad RI;

TAX 324 Study Group. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med 2007;357:

1705-15. doi: 10.1056/NEJMoa070956.

2. Johnson NW, Jayasekara P, Amarasinghe AA. Squamous cell carcinoma and precursor lesions of the oral cavity: epidemiol- ogy and aetiology. Periodontol 2000 2011;57:19-37. doi: 10.

1111/j.1600-0757.2011.00401.x.

3. Neville BW, Day TA. Oral cancer and precancerous lesions. CA Cancer J Clin 2002;52:195-215. doi: 10.3322/canjclin.52.4.195.

4. Scully C, Porter S. ABC of oral health. Oral cancer. BMJ 2000;

321:97-100. doi: 10.1136/bmj.321.7253.97.

5. Wolf VG, Bonacorsi C, Raddi MSG, da Fonseca LM, Ximenes VF. Octyl gallate, a food additive with potential beneficial properties to treat Helicobacter pylori infection. Food Funct 2017;8:2500-11. doi: 10.1039/c7fo00707h.

6. Khaledi H, Alhadi AA, Yehye WA, Ali HM, Abdulla MA, Has- sandarvish P. Antioxidant, cytotoxic activities, and structure- activity relationship of gallic acid-based indole derivatives.

Arch Pharm (Weinheim) 2011;344:703-9. doi: 10.1002/ardp.

201000223.

7. Serrano A, Palacios C, Roy G, Cesp ón C, Villar ML, Nocito M, Gonz ález-Porqué P. Derivatives of gallic acid induce apoptosis in tumoral cell lines and inhibit lymphocyte proliferation. Arch Biochem Biophys 1998;350:49-54. doi: 10.1006/abbi.1997.

0474.

8. Sales MS, Roy A, Antony L, Banu SK, Jeyaraman S, Manik- kam R. Octyl gallate and gallic acid isolated from Terminalia bellarica regulates normal cell cycle in human breast cancer cell lines. Biomed Pharmacother 2018;103:1577-84. doi: 10.

1016/j.biopha.2018.04.182.

9. de Cordova CA, Locatelli C, Assun ção LS, Mattei B, Mascarello A, Winter E, Nunes RJ, Yunes RA, Creczynski-Pasa TB. Octyl and dodecyl gallates induce oxidative stress and apoptosis in a melanoma cell line. Toxicol In Vitro 2011;25:2025-34. doi:

10.1016/j.tiv.2011.08.003.

10. Harburger DS, Calderwood DA. Integrin signalling at a glance.

J Cell Sci 2009;122(Pt 2):159-63. doi: 10.1242/jcs.018093.

11. Schwartz MA, Assoian RK. Integrins and cell proliferation:

regulation of cyclin-dependent kinases via cytoplasmic sig- naling pathways. J Cell Sci 2001;114(Pt 14):2553-60.

12. Lee J, Hong J, Nam TG, Peters EC, Orth AP, Geierstanger BH, Goldfinger LE, Ginsberg MH, Cho CY, Schultz PG. A small molecule inhibitor of alpha4 integrin-dependent cell migration.

Bioorg Med Chem 2009;17:977-80. doi: 10.1016/j.bmc.2008.

(7)

02.067.

13. Lu TN, Ganganna B, Pham TT, Vo AV, Lu TP, Nguyen HT, Nguyen MT, Huynh PN, Truong NT, Lee J. Antitumor effect of the integrin α4 signaling inhibitor JK273 in non-small cell lung cancer NCI-H460 cells. Biochem Biophys Res Commun 2017;491:355-60. doi: 10.1016/j.bbrc.2017.07.096.

14. Sui X, Kong N, Ye L, Han W, Zhou J, Zhang Q, He C, Pan H.

p38 and JNK MAPK pathways control the balance of apoptosis and autophagy in response to chemotherapeutic agents. Can- cer Lett 2014;344:174-9. doi: 10.1016/j.canlet.2013.11.019.

15. Lu Z, Xu S. ERK1/2 MAP kinases in cell survival and apop-

tosis. IUBMB Life 2006;58:621-31. doi: 10.1080/15216540 600957438.

16. Vilela B, Pag ès M, Lumbreras V. Regulation of MAPK signal- ing and cell death by MAPK phosphatase MKP2. Plant Signal Behav 2010;5:1497-500. doi: 10.4161/psb.5.11.13645.

17. Tang D, Wu D, Hirao A, Lahti JM, Liu L, Mazza B, Kidd VJ, Mak TW, Ingram AJ. ERK activation mediates cell cycle arrest and apoptosis after DNA damage independently of p53. J Biol Chem 2002;277:12710-7. doi: 10.1074/jbc.M111598200.

18. Eliceiri BP. Integrin and growth factor receptor crosstalk. Circ

Res 2001;89:1104-10. doi: 10.1161/hh2401.101084.

수치

Fig. 2.  The octyl gallate (OG) effects on cell cycle regulators. Cells were treated with various concentrations of OG from 0 to 150 µM for 24 hours
Fig. 4. Octyl gallate (OG) caused DNA damage on FaDu cells. (A) Cells  were treated with various concentrations of OG for 24 hours, and then  proteins were detected by western blotting
Fig. 5. Octyl gallate (OG) suppressed the expression of integrin family proteins. (A) FaDu cells were treated with OG for 24 hours

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