Top

Published in:

01-08-2021 | Oral Cancer | Review Article

Resveratrol effects in oral cancer cells: a comprehensive review

Authors: Tamires Cunha Almeida, Glenda Nicioli da Silva, Daniel Vitor de Souza, Andrea Cristina de Moraes Malinverni, Odair Aguiar Jr, Debora Estadella, Daniel Araki Ribeiro

Published in: Medical Oncology | Issue 8/2021

Abstract

Oral cancer is a very common tumor worldwide with high incidence and mortality. The treatment of oral cancer involves surgery, radio- and chemotherapy; however, high failure rates and toxicity are noticed. Thus, the search of new drugs aiming a more effective treatment is welcomed. Natural products present chemopreventive and anti-cancer effects. Resveratrol is a naturally occurring antioxidant that contains several health benefits, including anti-inflammatory and antiproliferative activities. This review discusses the different action mechanisms of resveratrol related in the in vitro and in vivo studies using models of oral cancer.

Jitender S, Sarika G, Varada HR, Omprakash Y, Mohsin K. Screening for oral cancer. J Exp Ther Oncol. 2016;11(4):303–7 (PMID: 27849341).PubMed

Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M, Znaor A, Bray F. Cancer statistics for the year 2020: an overview. Int J Cancer. 2021. https://doi.org/10.1002/ijc.33588 (Epub ahead of print. PMID: 33818764).CrossRefPubMed

Kumar M, Nanavati R, Modi TG, Dobariya C. Oral cancer: etiology and risk factors: a review. J Cancer Res Ther. 2016;12(2):458–63. https://doi.org/10.4103/0973-1482.186696 (PMID: 27461593).CrossRefPubMed

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30. https://doi.org/10.3322/caac.21590 (Epub 2020 Jan 8. PMID: 31912902).CrossRef

Kato MG, Baek CH, Chaturvedi P, Gallagher R, Kowalski LP, Leemans CR, Warnakulasuriya S, Nguyen SA, Day TA. Update on oral and oropharyngeal cancer staging—International perspectives. World J Otorhinolaryngol Head Neck Surg. 2020;6(1):66–75. https://doi.org/10.1016/j.wjorl.2019.06.001 (PMID:32426706;PMCID:PMC7221211).CrossRefPubMedPubMedCentral

Irani S. Distant metastasis from oral cancer: a review and molecular biologic aspects. J Int Soc Prev Community Dent. 2016;6(4):265–71. https://doi.org/10.4103/2231-0762.186805 (PMID: 27583211; PMCID: PMC4981925).CrossRefPubMedPubMedCentral

Irani S. Metastasis to head and neck area: a 16-year retrospective study. Am J Otolaryngol. 2011;32(1):24–7. https://doi.org/10.1016/j.amjoto.2009.09.006 (Epub 2009 Dec 23. PMID: 20031269).CrossRefPubMed

Rivera C. Essentials of oral cancer. Int J Clin Exp Pathol. 2015;8(9):11884–94.PubMedPubMedCentral

Huang SH, O’Sullivan B. Oral cancer: current role of radiotherapy and chemotherapy. Med Oral Patol Oral Cir Bucal. 2013;18(2):e233–40. https://doi.org/10.4317/medoral.18772 (PMID:23385513;PMCID:PMC3613874).CrossRefPubMedPubMedCentral

10.

Xie A, Liu J. Chemoprevention of oral cancer in leukoplakia patients: a systematic review and meta-analysis. J Pak Med Assoc. 2017;67(9):1415–9 (PMID: 28924285).PubMed

11.

Harvey AL, Edrada-Ebel R, Quinn RJ. The re-emergence of natural products for drug discovery in the genomics era. Nat Rev Drug Discov. 2015;14(111–129):2015. https://doi.org/10.1038/nrd4510.CrossRef

12.

Valletta A, Iozia LM, Leonelli F. Impact of environmental factors on stilbene biosynthesis. Plants (Basel). 2021;10(1):90. https://doi.org/10.3390/plants10010090.CrossRef

13.

Farhadi K, Esmaeilzadeh F, Hatami M, Forough M, Molaie R. Determination of phenolic compounds content and antioxidant activity in skin, pulp, seed, cane and leaf of five native grape cultivars in West Azerbaijan province. Iran Food Chem. 2016;15(199):847–55. https://doi.org/10.1016/j.foodchem.2015.12.083.CrossRef

14.

Tokuşoglu O, Unal MK, Yemiş F. Determination of the phytoalexin resveratrol (3,5,4’-trihydroxystilbene) in peanuts and pistachios by high-performance liquid chromatographic diode array (HPLC-DAD) and gas chromatography-mass spectrometry (GC-MS). J Agric Food Chem. 2005;53(12):5003–9. https://doi.org/10.1021/jf050496+.CrossRefPubMed

15.

Wang SY, Chen CT, Wang CY, Chen P. Resveratrol content in strawberry fruit is affected by preharvest conditions. J Agric Food Chem. 2007;55(20):8269–74. https://doi.org/10.1021/jf071749x.CrossRefPubMed

16.

Song W, Wang HJ, Bucheli P, Zhang PF, Wei DZ, Lu YH. Phytochemical profiles of different mulberry (Morus sp.) species from China. J Agric Food Chem. 2009;57(19):9133–40. https://doi.org/10.1021/jf9022228.CrossRefPubMed

17.

Lippi G, Franchini M, Favaloro EJ, Targher G. Moderate red wine consumption and cardiovascular disease risk: beyond the French Paradox. Semin Thromb Hemost. 2010;36:59–70. https://doi.org/10.1055/s-0030-1248725.CrossRefPubMed

18.

Sinha D, Sarkar N, Biswas J, Bishayee A. Resveratrol for breast cancer prevention and therapy: preclinical evidence and molecular mechanisms. Semin Cancer Biol. 2016;40–41:209–32. https://doi.org/10.1016/j.semcancer.2015.11.001.CrossRefPubMed

19.

Silk N, Reich J, Sinha R, Chawla S, Geary K, Zhang D. The effects of resveratrol on prostate cancer through targeting the tumor microenvironment. J Xenobiot. 2021;11(1):16–32. https://doi.org/10.3390/jox11010002.CrossRefPubMedPubMedCentral

20.

Yousef M, Vlachogiannis IA, Tsiani E. Effects of resveratrol against lung cancer: in vitro and in vivo studies. Nutrients. 2017;9(11):1231. https://doi.org/10.3390/nu9111231.CrossRefPubMedCentral

21.

Honari M, Shafabakhsh R, Reiter RJ, Mirzaei H, Asemi Z. Resveratrol is a promising agent for colorectal cancer prevention and treatment: focus on molecular mechanisms. Cancer Cell Int. 2019;15(19):180. https://doi.org/10.1186/s12935-019-0906-y.CrossRef

22.

Liang ZJ, Wan Y, Zhu DD, Wang MX, Jiang HM, Huang DL, Luo LF, Chen MJ, Yang WP, Li HM, Wei CY. Resveratrol mediates the apoptosis of triple negative breast cancer cells by reducing POLD1 expression. Front Oncol. 2021;25(11):569295. https://doi.org/10.3389/fonc.2021.569295.CrossRef

23.

Wu H, Chen L, Zhu F, Han X, Sun L, Chen K. The cytotoxicity effect of resveratrol: cell cycle arrest and induced apoptosis of breast cancer 4T1 cells. Toxins (Basel). 2019;11(12):731. https://doi.org/10.3390/toxins11120731.CrossRef

24.

Sun X, Xu Q, Zeng L, Xie L, Zhao Q, Xu H, Wang X, Jiang N, Fu P, Sang M. Resveratrol suppresses the growth and metastatic potential of cervical cancer by inhibiting STAT3(Tyr705) phosphorylation. Cancer Med. 2020;9(22):8685–700. https://doi.org/10.1002/cam4.3510.CrossRefPubMedPubMedCentral

25.

Zhang W, Jiang H, Chen Y, Ren F. Resveratrol chemosensitizes adriamycin-resistant breast cancer cells by modulating miR-122-5p. J Cell Biochem. 2019;120(9):16283–92. https://doi.org/10.1002/jcb.28910.CrossRefPubMed

26.

Berta NB, Salamone P, Sprio AE, Scipio FD, Marinos LM, Sapino S, Carlotti ME, Cavalli R, Di Carlo F. Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch by topical application of resveratrol complexed with 2-hydroxypropyl-beta-cyclodextrin. Oral Oncol. 2010;46(1):42–8.CrossRef

27.

Hu FW, Tsai LL, Yu CH, Chen PN, Chou MY, Yu CC. Impairment of tumor-initiating stem-like property and reversal of epithelial-mesenchymal transdifferentiation in head and neck cancer by resveratrol treatment. Mol Nutr Food Res. 2012;56(8):1247–58.CrossRef

28.

Chang CH, Lee CY, Lu CC, Tsai FJ, Hsu YM, Tsao JW, Juan YN, Chiu HY, Yang JS, Wang CC. Resveratrol-induced autophagy and apoptosis in cisplatin-resistant human oral cancer CAR cells: A key role of AMPK and Akt/mTOR signaling. Int J Oncol. 2017;50(3):873–82.CrossRef

29.

Kim SE, Shin SH, Lee JY, Kim CH, Chung IK, Kang HM, Park HR, Park BS. Kim IR resveratrol induces mitochondrial apoptosis and inhibits epithelial-mesenchymal transition in oral squamous cell carcinoma cells. Nutr Cancer. 2018;70(1):125–35.CrossRef

30.

Chen L, Xia JS, Wu JH, Chen YG, Qiu CJ. Resveratrol inhibits oral squamous cell carcinoma cells proliferation while promoting apoptosis through inhibition of CBX7 protein. Environ Toxicol. 2020;35(11):1234–40.CrossRef

31.

Singh V, Singh R, Kujur PK, Singh RP. Combination of resveratrol and quercetin causes cell growth inhibition, DNA damage, cell cycle arrest, and apoptosis in oral cancer cells. Assay Drug Dev Technol. 2020;18(5):226–38.CrossRef

32.

Chen YR, Chen YS, Chin YT, Li ZL, Shih YJ, Yang YSH, ChangOu CA, Su PY, Wang SH, Wu YH, Chiu HC, Lee SY, Liu LF, Whang-Peng J, Lin HY, Mousa SA, Davis PJ, Wang K. Thyroid hormone-induced expression of inflammatory cytokines interfere with resveratrol-induced anti-proliferation of oral cancer cells. Food Chem Toxicol. 2019;132:110693.CrossRef

33.

Yu XD, Yang JL, Zhang WL, Liu DX. Resveratrol inhibits oral squamous cell carcinoma through induction of apoptosis and G2/M phase cell cycle arrest. Tumour Biol. 2016;37(3):2871–7.CrossRef

34.

Hayashi F, Kasamatsu A, Endo-Sakamoto Y, Eizuka K, Hiroshima K, Kita A, Saito T, Koike K, Tanzawa H, Uzawa K. Increased expression of tripartite motif (TRIM) like 2 promotes tumoral growth in human oral cancer. Biochem Biophys Commun. 2019;508(4):1133–8.CrossRef

35.

Pradhan R, Chatterjee S, Hembram KC, Sethy C, Mandal M, Kundu CN. Nano formulated resveratrol inhibits metastasis and angiogenesis by reducing inflammatory cytokines in oral cancer cells by targeting tumor associated macrophages. J Nutr Biochem. 2021;92:108624.CrossRef

36.

Biesaga B, Kołodziej-Rzepa M, Janecka-Widła A, Słonina D, Halaszka K, Przewoźnik M, Mucha-Małecka A. Lack of CD44 overexpression and application of concurrent chemoradiotherapy with cisplatin independently indicate excellent prognosis in patients with HPV-positive oropharyngeal cancer. Tumour Biol. 2021;43(1):99–113.CrossRef

37.

Tu DG, Lin WT, Yu CC, Lee SS, Peng CY, Lin T, Yu CH. Chemotherapeutic effects of luteolin on radio-sensitivity enhancement and interleukin-6/signal transducer and activator of transcription 3 signaling repression of oral cancer stem cells. J Formos Med Assoc. 2016;115(12):1032–8.CrossRef

38.

Shan Z, Yang G, Xiang W, Pei-jun W, Bin Z. Effects of resveratrol on oral squamous cell carcinoma (OSCC) cells in vitro. J Cancer Res Clin Oncol. 2014;140(3):371–4.CrossRef

39.

Hsieh MJ, Chin MC, Lin CC, His YT, Lo YS, Chuang YC, Chen MK. pinostilbene hydrate suppresses human oral cancer cell metastasis by downregulation of matrix metalloproteinase-2 through the mitogen-activated protein kinase signaling pathway. Cell Physiol Biochem. 2018;50(3):911–23.CrossRef

40.

Lin FY, Hsieh YH, Yang SF, Chen CT, Tang CH, Chou MY, Chuang YT, Lin CW, Chen MK. Resveratrol suppresses TPA-induced matrix metalloproteinase-9 expression through the inhibition of MAPK pathways in oral cancer cells. J Oral Pathol Med. 2015;44(9):699–706.CrossRef

41.

Ribeiro DA, Salvadori DM, Marques ME. Abnormal expression of bcl-2 and bax in rat tongue mucosa during the development of squamous cell carcinoma induced by 4-nitroquinoline 1-oxide. Int J Exp Pathol. 2005;86(6):375–81.CrossRef

42.

Gonçalves Vde P, Ortega AA, Guimarães MR, Curylofo FA, Rossa Junior C, Ribeiro DA, Spolidorio LC. Chemopreventive activity of systemically administered curcumin on oral cancer in the 4-nitroquinoline 1-oxide model. J Cell Biochem. 2015;116(5):787–96.CrossRef

43.

Ho Y, Wu CY, Chin YT, Li ZL, Pan YS, Huang TY, Su PY, Lee SY, Crawford DR, Su KW, Chiu HC, Shih YJ, Changou CA, Yang YSH, Whang-Peng J, Chen YR, Lin HY, Mousa SA, Davis PJ, Wang K. NDAT suppresses pro-inflammatory gene expression to enhance resveratrol-induced anti-proliferation in oral cancer cells. Food Chem Toxicol. 2020;136:111092.CrossRef

44.

Dukaew N, Chairatvit K, Pitchakarn P, Imsumran A, Karinchai J, Tuntiwechapikul W, Wongnoppavich A. Inactivation of AKT/NF-kappaB signaling by eurycomalactone decreases human NSCLC cell viability and improves the chemosensitivity to cisplatin. Oncol Rep. 2020;44(4):1441–54.PubMedPubMedCentral

45.

Masuelli L, Di Stefano E, Fantini M, Mattera R, Benvenuto M, Marzocchella L, Sacchetti P, Focaccetti C, Bernardini R, Tresoldi I, Izzi V, Mattei M, Frajese GV, Lista F, Modesti A, Bei R. Resveratrol potentiates the in vitro and in vivo anti-tumoral effects of curcumin in head and neck carcinomas. Oncotarget. 2014;5(21):10745–62.CrossRef

46.

Chang HJ, Chou CT, Chang HT, Liang WZ, Hung TY, Li YD, Fang YC, Kuo CC, Kuo DH, Shieh P, Jan CR. Mechanisms of resveratrol-induced changes in cytosolic free calcium ion concentrations and cell viability in OC2 human oral cancer cells. Hum Exp Toxicol. 2015;34(3):289–99.CrossRef

47.

Wang S, Zhang Y, Huang J, Wong CC, Zhai J, Li C, Wei G, Zhao L, Wang G, Wei H, Zhao Z. Yu JTRIM67 Activates p53 to suppress colorectal cancer initiation and progression. Cancer Res. 2019;79(16):4086–98.PubMed

48.

Kim JY, Cho KH, Jeong BY, Park CG, Lee HY. Zeb1 for RCP-induced oral cancer cell invasion and its suppression by resveratrol. Exp Mol Med. 2020;52(7):1152–63.CrossRef

49.

de Kort WWB, Spelier S, Devriese LA, van Es RJJ, Willems SM. Predictive value of EGFR-PI3K-AKT-mTOR-pathway inhibitor biomarkers for head and neck squamous cell carcinoma: a systematic review. Mol Diagn Ther. 2021;25(2):123–36.CrossRef

50.

Shrotriya S, Tyagi A, Deep G, Orlicky DJ, Wisell J, Wang XJ, Sclafani RA, Agarwal R, Agarwal C. Grape seed extract and resveratrol prevent 4-nitroquinoline 1-oxide induced oral tumorigenesis in mice by modulating AMPK activation and associated biological responses. Mol Carcinog. 2015;54(4):291–300.CrossRef

51.

Atienzar AN, Camacho-Alonso F, Lopez-Jornet P. Effects of resveratrol and irradiation upon oral squamous cell carcinoma cells. Acta Odontol Scand. 2014;72(7):481–8.CrossRef

52.

Sheng H, Ogawa T, Niwano Y, Sasaki K, Tachibana K. Effects of polyphenols on doxorubicin-induced oral keratinocyte cytotoxicity and anticancer potency against oral cancer cells. J Oral Pathol Med. 2018;47(4):368–74.CrossRef

53.

Tomikoshi Y, Nomura M, Okidaira N, Sakagami H, Wakabayashi H. Enhancement of cytotoxicity of three apoptosis-inducing agents against human oral squamous cell carcinoma cell line by benzoxazinotropone. In Vivo. 2016;30(5):645–50.PubMed

54.

Uzawa K, Amelio AL, Kasamatsu A, Saito T, Kita A, Fukamachi M, Sawai Y, Toeda Y, Eizuka K, Hayashi F, Kato-Kase I, Sunohara M, Iyoda M, Koike K, Nakashima D, Ogawara K, Endo-Sakamoto Y, Shiiba M, Takiguchi Y, Yamauchi M, Tanzawa H. Resveratrol targets urokinase-type plasminogen activator receptor expression to overcome cetuximab-resistance in oral squamous cell carcinoma. Sci Rep. 2019;9(1):12179.CrossRef

55.

Annaji M, Poudel I, Boddu SHS, Arnold RD, Tiwari AK, Babu RJ. Resveratrol-loaded nanomedicines for cancer applications. Cancer Rep. 2021;2:e1353. https://doi.org/10.1002/cnr2.1353.CrossRef

56.

Zhu W, Qin W, Zhang K, Rottinghaus GE, Chen YC, Kliethermes B, Sauter ER. Trans-resveratrol alters mammary promoter hypermethylation in women at increased risk for breast cancer. Nutr Cancer. 2012;64(3):393–400.CrossRef

57.

Patel KR, Brown VA, Jones DJ, Britton RG, Hemingway D, Miller AS, West KP, Booth TD, Perloff M, Crowell JA, Brenner DE, Steward WP, Gescher AJ, Brown K. Clinical pharmacology of resveratrol and its metabolites in colorectal cancer patients. Cancer Res. 2010;70(19):7392–9.CrossRef

58.

Howells LM, Berry DP, Elliott PJ, Jacobson EW, Hoffmann E, Hegarty B, Brown K, Steward WP, Gescher AJ. Phase I randomized, double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases–safety, pharmacokinetics, and pharmacodynamics. Cancer Prev Res. 2011;4(9):1419–25.CrossRef

59.

Almeida L, Vaz-da-Silva M, Falcão A, Soares E, Costa R, Loureiro AI, Fernandes-Lopes C, Rocha JF, Nunes T, Wright L, et al. Pharmacokinetic and safety profile of trans-resveratrol in a rising multiple-dose study in healthy volunteers. Mol Nutr Food Res. 2009;53:7–15.CrossRef

60.

Brown VA, Patel KR, Viskaduraki M, Crowell JA, Perloff M, Boo TD, Vasilinin G, Sen A, Schinas AM, Piccirilli G, et al. Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis. Cancer Res. 2010;70:9003–11.CrossRef

Title: Resveratrol effects in oral cancer cells: a comprehensive review
Authors: Tamires Cunha Almeida
Glenda Nicioli da Silva
Daniel Vitor de Souza
Andrea Cristina de Moraes Malinverni
Odair Aguiar Jr
Debora Estadella
Daniel Araki Ribeiro
Publication date: 01-08-2021
Publisher: Springer US
Keywords: Oral Cancer
Oral Cavity Carcinoma
Published in: Medical Oncology / Issue 8/2021
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI: https://doi.org/10.1007/s12032-021-01548-0

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Resveratrol effects in oral cancer cells: a comprehensive review

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 8/2021

Computational study on novel natural inhibitors targeting BCL2

Can the host immune response against SARS-CoV2 also cause an anticancer effect?

ARA-linker-TGFαL3: a novel chimera protein to target breast cancer cells

Upregulation of apoptotic protease activating factor-1 expression correlates with anti-tumor effect of taxane drug

Vaccination of cancer patients against COVID-19: towards the end of a dilemma

Levofloxacin might be safe to use for OSCC patients

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page