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Current Signal Transduction Therapy

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ISSN (Print): 1574-3624
ISSN (Online): 2212-389X

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Research Article

Combination of Probiotics and Resveratrol to Target Drug Resistance in Breast Cancer: An In vitro and In vivo Study

Author(s): Faten Farhan and Wamidh H. Talib*

Volume 18, Issue 2, 2023

Published on: 07 April, 2023

Article ID: e280223214150 Pages: 11

DOI: 10.2174/1574362418666230228122251

Price: $65

Abstract

Background: Probiotics exhibit significant activity in the immune system by activating multiple immune mechanisms. Resveratrol is a non-flavonoid polyphenol. It has various pharmacological effects, including anti-oxidative, anti-inflammatory, anti-proliferative, and anti-angiogenesis effects.

Objectives: The present study investigates the potential immunomodulatory and antitumor activity of the combination treatment of probiotics and resveratrol in sensitive and cisplatin-resistant breast cancer.

Methods: In the in vivo study, tumor-bearing mice received one of the following treatments: 2.5*108 CFU/ml probiotics, 50 mg/kg resveratrol, the combination of probiotics and resveratrol, vehicle, or cisplatin. Balb/C mice were inoculated with sensitive EMT6/P and cisplatin resistance EMT6/CPR cancer cell lines, and in vivo antitumor activity was evaluated.

Results: The antiproliferative activity of the probiotics, resveratrol, and their combination treatments was assessed using an MTT assay to evaluate lymphocyte proliferation activity. LDH colorimetric assay was conducted to measure the effectiveness of the treatments on the activity of natural killer cells. Nitro blue tetrazolium assay and neutral red method were used to evaluate macrophage function.

Conclusion: The combination treatment showed an enhanced effect in splenic lymphocyte proliferation, macrophage function, phagocytosis, and pinocytosis in both cell lines. A significant reduction in tumor size and weight in EMT6/P and EMT6/CPR-bearing mice occurred. Hence, the combination treatment of probiotics and resveratrol was found to have a valuable activity against sensitive and cisplatin-resistant breast cancer cells and might act as a stimulator of the immune system. Therefore, the combination of probiotics and resveratrol deserves further analysis to be used in cancer prevention and treatment.

Keywords: Probiotics, resveratrol, breast cancer, immunomodulatory, drug resistance, antitumor activity.

Graphical Abstract

[1]
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016; 66(1): 7-30.
[http://dx.doi.org/10.3322/caac.21332] [PMID: 26742998]
[2]
McGuire S. International agency for research on cancer. World health organizarion. World cancer report 2014. World cancer report 2014. Adv Nutr 2016; 7: 418-9.
[http://dx.doi.org/10.3945/an.116.012211] [PMID: 26980827]
[3]
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6): 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[4]
Turati F, Rossi M, Pelucchi C, Levi F, La Vecchia C. Fruit and vegetables and cancer risk: a review of southern European studies. Br J Nutr 2015; 113(S2): S102-10.
[http://dx.doi.org/10.1017/S0007114515000148] [PMID: 26148912]
[5]
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144(5): 646-74.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[6]
Yuan R, Hou Y, Sun W, et al. Natural products to prevent drug resistance in cancer chemotherapy: a review. Ann N Y Acad Sci 2017; 1401(1): 19-27.
[http://dx.doi.org/10.1111/nyas.13387] [PMID: 28891091]
[7]
Ochwang’i DO, Kimwele CN, Oduma JA, Gathumbi PK, Mbaria JM, Kiama SG. Medicinal plants used in treatment and management of cancer in Kakamega County, Kenya. J Ethnopharmacol 2014; 151(3): 1040-55.
[http://dx.doi.org/10.1016/j.jep.2013.11.051] [PMID: 24362078]
[8]
Catalgol B, Batirel S, Taga Y, Ozer NK. Resveratrol: French paradox revisited. Front Pharmacol 2012; 3: 141.
[http://dx.doi.org/10.3389/fphar.2012.00141] [PMID: 22822401]
[9]
Talib WH, Alsayed AR, Farhan F, Al Kury LT. Resveratrol and tumor microenvironment: mechanistic basis and therapeutic targets. Molecules 2020; 25(18): 4282.
[http://dx.doi.org/10.3390/molecules25184282] [PMID: 32961987]
[10]
Fuller R. Probiotics in human medicine. Gut 1991; 32(4): 439-2.
[http://dx.doi.org/10.1136/gut.32.4.439]
[11]
Maldonado Galdeano C, Cazorla SI, Lemme Dumit JM, Vélez E. Perdigَn G. Beneficial effects of probiotic consumption on the immune system. Ann Nutr Metab 2019; 74(2): 115-24.
[http://dx.doi.org/10.1159/000496426] [PMID: 30673668]
[12]
Verma A, Shukla G. Probiotics Lactobacillus rhamnosus GG, Lactobacillus acidophilus suppresses DMH-induced procarcinogenic fecal enzymes and preneoplastic aberrant crypt foci in early colon carcinogenesis in Sprague Dawley rats. Nutr Cancer 2013; 65(1): 84-91.
[http://dx.doi.org/10.1080/01635581.2013.741746] [PMID: 23368917]
[13]
Yazdi MH, Soltan Dallal MM, Hassan ZM, et al. Oral administration of Lactobacillus acidophilus induces IL-12 production in spleen cell culture of BALB/c mice bearing transplanted breast tumour. Br J Nutr 2010; 104(2): 227-32.
[http://dx.doi.org/10.1017/S0007114510000516] [PMID: 20193099]
[14]
Yazdi M, Mahdavi M, Kheradmand E, Shahverdi A. The preventive oral supplementation of a selenium nanoparticle-enriched probiotic increases the immune response and lifespan of 4T1 breast cancer bearing mice. Arzneimittelforschung 2012; 62(11): 525-31.
[http://dx.doi.org/10.1055/s-0032-1323700] [PMID: 22945771]
[15]
Talib W, Mahasneh A. Combination of Ononis hirta and Bifidobacterium longum decreases syngeneic mouse mammary tumor burden and enhances immune response. J Cancer Res Ther 2012; 8(3): 417-23.
[http://dx.doi.org/10.4103/0973-1482.103523] [PMID: 23174725]
[16]
Mahajan SD, Law WC, Aalinkeel R, et al. Nanoparticle-mediated targeted delivery of antiretrovirals to the brain. (1st ed.), Amsterdam: Elsevier Inc. 2012.
[http://dx.doi.org/10.1016/B978-0-12-391858-1.00003-4]
[17]
Ray A, Dittel BN. Isolation of mouse peritoneal cavity cells. J Vis Exp 2010; (35): 1488.
[PMID: 20110936]
[18]
Boothapandi M, Ramanibai R. Immunomodulatory activity of Indigofera tinctoria leaf extract on in vitro macrophage responses and lymphocyte proliferation. Int J Pharm Pharm Sci 2016; 8: 58-63.
[19]
Esteban MA, Mulero V. Muٌoz J, Meseguer J. Methodological aspects of assessing phagocytosis of Vibrio anguillarum by leucocytes of gilthead seabream (Sparus aurata L.) by flow cytometry and electron microscopy. Cell Tissue Res 1998; 293(1): 133-41.
[http://dx.doi.org/10.1007/s004410051105] [PMID: 9634605]
[20]
Emens LA, Ascierto PA, Darcy PK, et al. Cancer immunotherapy: Opportunities and challenges in the rapidly evolving clinical landscape. Eur J Cancer 2017; 81: 116-29.
[http://dx.doi.org/10.1016/j.ejca.2017.01.035] [PMID: 28623775]
[21]
Talib WH. A ketogenic diet combined with melatonin overcomes cisplatin and vincristine drug resistance in breast carcinoma syngraft. Nutrition 2020; 72: 110659.
[http://dx.doi.org/10.1016/j.nut.2019.110659] [PMID: 31986320]
[22]
D WHTP Consumption of garlic and lemon aqueous extracts combination reduce tumor burden by angiogenesis inhibition, apoptosis induction, and immune system modulation Consumption of garlic and lemon aqueous extracts combination reduces tumor burden by angiogene. Nutrition 2017; 43–44: 89-97.
[23]
Legesse Bedada T, Feto TK, Awoke KS, Garedew AD, Yifat FT, Birri DJ. Probiotics for cancer alternative prevention and treatment. Biomed Pharmacother 2020; 129: 110409.
[http://dx.doi.org/10.1016/j.biopha.2020.110409] [PMID: 32563987]
[24]
Shukla Y, Singh R. Resveratrol and cellular mechanisms of cancer prevention. Ann N Y Acad Sci 2011; 1215(1): 1-8.
[http://dx.doi.org/10.1111/j.1749-6632.2010.05870.x] [PMID: 21261635]
[25]
Alobaedi OH, Talib WH, Basheti IA. Antitumor effect of thymoquinone combined with resveratrol on mice transplanted with breast cancer. Asian Pac J Trop Med 2017; 10(4): 400-8.
[http://dx.doi.org/10.1016/j.apjtm.2017.03.026] [PMID: 28552110]
[26]
Vervandier-Fasseur D, Latruffe N. The potential use of resveratrol for cancer prevention. Molecules 2019; 24(24): 4506.
[http://dx.doi.org/10.3390/molecules24244506] [PMID: 31835371]
[27]
Li W, Li C, Ma L, Jin F. Resveratrol inhibits viability and induces apoptosis in the small cell lung cancer H446 cell line via the PI3K/Akt/c Myc pathway. Oncol Rep 2020; 44(5): 1821-30.
[http://dx.doi.org/10.3892/or.2020.7747] [PMID: 32901891]
[28]
Delmas D, Rébé C, Micheau O, et al. Redistribution of CD95, DR4 and DR5 in rafts accounts for the synergistic toxicity of resveratrol and death receptor ligands in colon carcinoma cells. Oncogene 2004; 23(55): 8979-86.
[http://dx.doi.org/10.1038/sj.onc.1208086] [PMID: 15480430]
[29]
Zhao W, Bao P, Qi H, You H. Resveratrol down-regulates survivin and induces apoptosis in human multidrug-resistant SPC-A-1/CDDP cells. Oncol Rep 2010; 23(1): 279-86.
[PMID: 19956893]
[30]
Mukherjee S, Dudley JI, Das DK. Dose-dependency of resveratrol in providing health benefits Dose Response 2010; 8(4): doseresponse.0.
[http://dx.doi.org/10.2203/dose-response.09-015.Mukherjee] [PMID: 21191486]
[31]
Bermudez-humaran LG, Jacouton E, Michel M, et al. Elucidating the immune-related mechanisms by which probiotic strain Lactobacillus casei BL23 displays anti-tumoral properties. FRIN 2018; 9: 3281.
[http://dx.doi.org/10.3389/fmicb.2018.03281]
[32]
Li J, Sung CYJ, Lee N, et al. Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice. Proc Natl Acad Sci 2016; 113: E1306 LP-.
[http://dx.doi.org/10.1073/pnas.1518189113]
[33]
Kahouli I, Handiri NR. Characterization of L. reuteri NCIMB 701359 probiotic features for potential use as a colorectal cancer biotherapeutic by identifying fatty acid profile and anti-proliferative action against colorectal cancer cells. Drug Des 2016; 5(131): 2169-0138.
[http://dx.doi.org/10.4172/2169-0138.1000131]
[34]
Maroof H, Hassan ZM, Mobarez AM, Mohamadabadi MA. Lactobacillus acidophilus could modulate the immune response against breast cancer in murine model. J Clin Immunol 2012; 32(6): 1353-9.
[http://dx.doi.org/10.1007/s10875-012-9708-x] [PMID: 22711009]
[35]
Larosa D, Orange J. 1. Lymphocytes. J Allergy Clin Immunol 2008; 121(S2): S364-9.
[http://dx.doi.org/10.1016/j.jaci.2007.06.016] [PMID: 18241683]
[36]
Xu HS, Wu YW, Xu SF, Sun HX, Chen FY, Yao L. Antitumor and immunomodulatory activity of polysaccharides from the roots of Actinidia eriantha. J Ethnopharmacol 2009; 125(2): 310-7.
[http://dx.doi.org/10.1016/j.jep.2009.06.015] [PMID: 19559777]
[37]
Kirjavainen PV, El-Nezami HS, Salminen SJ, Ahokas JT, Wright PFA. The effect of orally administered viable probiotic and dairy lactobacilli on mouse lymphocyte proliferation. FEMS Immunol Med Microbiol 1999; 26(2): 131-5.
[http://dx.doi.org/10.1111/j.1574-695X.1999.tb01380.x] [PMID: 10536299]
[38]
Abdelrazek H, Yusuf M, Ismail S, Elgawish R. Effect of probiotic strains mixture administration on serum interleukins concentration, lymphocyte proliferation and DNA damage in rams. J Anim Feed Sci 2015; 24(4): 302-7.
[http://dx.doi.org/10.22358/jafs/65612/2015]
[39]
Lee J, Yun HS, Cho KW, et al. Evaluation of probiotic characteristics of newly isolated Lactobacillus spp.: Immune modulation and longevity. Int J Food Microbiol 2011; 148(2): 80-6.
[http://dx.doi.org/10.1016/j.ijfoodmicro.2011.05.003] [PMID: 21652104]
[40]
Hart AL, Lammers K, Brigidi P, et al. Modulation of human dendritic cell phenotype and function by probiotic bacteria. Gut 2004; 53(11): 1602-9.
[http://dx.doi.org/10.1136/gut.2003.037325] [PMID: 15479680]
[41]
Lai X, Pei Q, Song X, et al. The enhancement of immune function and activation of NF-κB by resveratrol-treatment in immunosuppressive mice. Int Immunopharmacol 2016; 33: 42-7.
[http://dx.doi.org/10.1016/j.intimp.2016.01.028] [PMID: 26854575]
[42]
Herberman RB. Natural killer cells. Annu Rev Med 1986; 37(1): 347-52.
[http://dx.doi.org/10.1146/annurev.me.37.020186.002023] [PMID: 3518610]
[43]
Li Q, Huyan T, Ye LJ, Li J, Shi JL, Huang QS. Concentration-dependent biphasic effects of resveratrol on human natural killer cells in vitro. J Agric Food Chem 2014; 62(45): 10928-35.
[http://dx.doi.org/10.1021/jf502950u] [PMID: 25360711]
[44]
Konjević G, Jurišić V, Spužić I. Corrections to the original lactate dehydrogenase (LDH) release assay for the evaluation of NK cell cytotoxicity. J Immunol Methods 1997; 200(1-2): 199-201.
[http://dx.doi.org/10.1016/S0022-1759(96)00194-9] [PMID: 9005959]
[45]
Maftouh M, Avan A, Sciarrillo R, et al. Synergistic interaction of novel lactate dehydrogenase inhibitors with gemcitabine against pancreatic cancer cells in hypoxia. Br J Cancer 2014; 110(1): 172-82.
[http://dx.doi.org/10.1038/bjc.2013.681] [PMID: 24178759]
[46]
Delcenserie V, Martel D, Lamoureux M, Amiot J, Boutin Y, Roy D. Immunomodulatory effects of probiotics in the intestinal tract. Curr Issues Mol Biol 2008; 10(1-2): 37-54.
[PMID: 18525105]
[47]
Zaynagetdinov R, Sherrill TP, Polosukhin VV, et al. A critical role for macrophages in promotion of urethane-induced lung carcinogenesis. J Immunol 2011; 187(11): 5703-11.
[http://dx.doi.org/10.4049/jimmunol.1100558] [PMID: 22048774]
[48]
Mantovani A, Marchesi F, Malesci A, Laghi L, Allavena P. Tumour-associated macrophages as treatment targets in oncology. Nat Rev Clin Oncol 2017; 14(7): 399-416.
[http://dx.doi.org/10.1038/nrclinonc.2016.217] [PMID: 28117416]
[49]
Xiang S. Endocytosis and human innate immunity. J Immunol Sci 2018; 2(1): 65-70.
[http://dx.doi.org/10.29245/2578-3009/2018/1.1121]
[50]
Koenen ME, Kramer J, van der Hulst R, Heres L, Jeurissen SHM, Boersma WJA. Immunomodulation by probiotic lactobacilli in layer-and meat-type chickens. Br Poult Sci 2004; 45(3): 355-66.
[http://dx.doi.org/10.1080/00071660410001730851] [PMID: 15327122]
[51]
Wang Y, Liu H, Zhao J. Macrophage polarization induced by probiotic bacteria: A concise review. Probiotics Antimicrob Proteins 2020; 12(3): 798-808.
[http://dx.doi.org/10.1007/s12602-019-09612-y] [PMID: 31741313]

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