Skip to main content

Advertisement

Log in

The ethanol extract of avocado [Persea americana Mill. (Lauraceae)] seeds reduced the hyperplastic effect of tamoxifen on uterine endometrium without changing its effect on the mammary gland

  • Research Article
  • Published:
Advances in Traditional Medicine Aims and scope Submit manuscript

Abstract

Tamoxifen is the most common hormonal treatment for estrogen receptor positive (ER+) breast cancer. However, the long-term use of tamoxifen was associated with increased risks of endometrial cancer. The literature suggests that combining tamoxifen with substances endowed with antiproliferative properties could increase tamoxifen’s chemopreventive benefit. The ethanol extract of Persea americana Mill. (Lauraceae) seeds was found exhibiting antiproliferative properties in vitro. The present study therefore aimed at evaluating the ability of such an extract to prevent tamoxifen-induced endometrial hyperplasia without changing its activity on the mammary gland. This study was performed in ovariectomized rats receiving simultaneously tamoxifen (by the intraperitoneal route) and the ethanol extract of P. americana seeds (by gavage) at doses of 25, 50, 100 and 200 mg/kg. Co-administrations were performed for 37 consecutive days and animals were sacrificed thereafter. Uterine and serum levels of estradiol and cholesterol were assessed. The oxidative status of the uterus was also evaluated. Histology of the uterus and the mammary gland was performed. Results showed that the ethanol extract of P. americana seeds did not alter tamoxifen-induced uterine steroidogenesis but reduced its proliferative effect by decreasing uterine epithelial height (p < 0.001). T his antiproliferative effect was associated with increased uterine levels of malondialdehyde and antioxidant enzymes. On the mammary gland, the non-proliferative effect of tamoxifen was not altered by P. americana extract. In conclusion, the ethanol extract of P. americana seeds could be a complementary treatment to prevent tamoxifen-induced endometrial hyperplasia during the treatment of ER+ breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Abubakar ANF, Achmadi SS, Suparto IH (2017) Triterpenoid of avocado (Persea americana) seed and its cytotoxic activity toward breast MCF-7 and liver HepG2 cancer cells. Asian Pac J Trop Biomed 7:385–504

    Google Scholar 

  • Adeyemi OO, Okpo SO, Ogunti OO (2002) Analgesic and anti-inflammatory effects of the aqueous extract of leaves of Persea americana Mill. (Lauraceae). Fitoterapia 73(5):375–380

    CAS  PubMed  Google Scholar 

  • American Cancer Society. Hormone therapy for Breast cancer in men. www.cancer.org/cancer/breast-cancer-in-men/treating/hormone-therapy.html. Accessed 10 Nov 2018.

  • Antia BS, Okokon JE, Okon PA (2005) Hypoglycemic activity of aqueous leaf extract of Persea americana Mill. Indian J Pharmacol 37(5):325

    Google Scholar 

  • Aydin A, Arsova-Sarafinovska Z, Sayal A, Eken A, Erdem O, Erten K, Ozgok Y, Dimovski A (2006) Oxidative stress and antioxidant status in non-metastatic prostate cancer and benign prostatic hyperplasia. Clin Biochem 39(2):176–179

    CAS  PubMed  Google Scholar 

  • Berg JM, Tymoczko JL, Stryer L (2002) Biochemistry, 5th edn. W. H. Freeman, New-York

    Google Scholar 

  • Bernkopf DB, Daum G, Brückner M, Behrens J (2018) Sulforaphane inhibits growth and blocks Wnt/β-catenin signaling of colorectal cancer cells. Oncotarget 9(74):33982–33994

    PubMed  PubMed Central  Google Scholar 

  • Bonilla-Porras AR, Salazar-Ospina A, Jimenez-Del-Rio M, Pereañez-Jimenez A, Velez-Pardo C (2014) Pro-apoptotic effect of Persea americana var. Hass (avocado) on Jurkat lymphoblastic leukemia cells. Pharm Biol 52(4):458–465

    Google Scholar 

  • Brown K (2002) Breast cancer chemoprevention: risk-benefit effects of the antioestrogen tamoxifen. Expert Opin Drug Saf 1:253–267

    CAS  PubMed  Google Scholar 

  • Burstein HJ, Temin S, Anderson H, Buchholz TA, Davidson NE, Gelmon KE, Giordano SH, Hudis CA, Rowden D, Solky AJ, Stearns V, Winer EP, Griggs JJ (2014) Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline Focused Update. J Clin Oncol 32(21):2255–2269

    PubMed  PubMed Central  Google Scholar 

  • Carthew P, Edwards RE, Noloan BM, Martin EA, Heydon RT, White IN, Tucker MJ (2000) Tamoxifen induces endometrial and vaginal cancer in rats in the absence of endometrial hyperplasia. Carcinogenesis 21:793–797

    CAS  PubMed  Google Scholar 

  • Das A, Mantenaa SR, Kannana A, Evans DB, Bagchi MK, Bagchi IC (2009) De novo synthesis of estrogen in pregnant uterus is critical for stromal decidualization and angiogenesis. Proc Natl Acad Sci USA 106:12542–12547

    CAS  PubMed  Google Scholar 

  • Ding H, Chin YW, Kinghorn AD, D'Ambrosio SM (2007) Chemopreventive characteristics of avocado fruit. Semin Cancer Biol 17(5):386–394

    PubMed  Google Scholar 

  • Ding H, Han C, Guo D, Chin YW, Ding Y, Kinghorn AD, D'Ambrosio SM (2009) Selective induction of apoptosis of human oral cancer cell lines by avocado extracts via a ROS-mediated mechanism. Nutr Cancer 61:348–356

    CAS  PubMed  Google Scholar 

  • Ding L, Zhao Y, Warren CL, Sullivan R, Eliceiri KW, Shull JD (2013) Association of cellular and molecular responses in the rat mammary gland to 17β-estradiol with susceptibility to mammary cancer. BMC Cancer 13:573

    PubMed  PubMed Central  Google Scholar 

  • Dnistrian AM, Schwartz MK, Greenberg EJ, Smith CA, Schwartz DC (1993) Effect of tamoxifen on serum cholesterol and lipoproteins during chemohormonal therapy. Clin Chim Acta 223(1–2):43–52

    CAS  PubMed  Google Scholar 

  • Duru R, Njoku O, Maduka I (2014) Oxidative stress indicators in patients with prostate disorders in Enugu South-East Nigeria. Biomed Res Int 2014:313015

    PubMed  PubMed Central  Google Scholar 

  • Feng L, Li J, Yang L, Zhu L, Huang X, Zhang S, Luo L, Jiang Z, Jiang T, Xu W, Wang X, Jin H (2017) Tamoxifen activates Nrf2-dependent SQSTM1 transcription to promote endometrial hyperplasia. Theranostics 7(7):1890–1900

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gruber CJ, Tschugguel W, Schneeberger C, Huber J (2002) Mechanism of disease: production and actions of estrogens. N Engl J Med 346(5):340–352

    CAS  PubMed  Google Scholar 

  • Gu W, Xu W, Sun X, Zeng B, Wang S, Dong N, Zhang X, Chen C, Yang L, Chen G, Xin A, Ni Z, Wang J, Yang J (2017) Anordrin eliminates tamoxifen side effects without changing its antitumor activity. Sci Rep 7:43940

    PubMed  PubMed Central  Google Scholar 

  • Habbu P, Shastry R, Mahadevan K, Hanumanthachar J, Das S (2008) Hepatoprotective and antioxidant effects of argyreia speciosa in rats. Afr J Tradit Complement Altern Med 5(2):158–164

    CAS  PubMed  PubMed Central  Google Scholar 

  • Huhtinen K, Desai R, Stahle M, Salminen A, Handelsman DJ, Perheentupa A, Poutanen M (2012) Endometrial and endometriotic concentrations of estrone and estradiol are determined by local metabolism rather than circulating levels. J Clin Endocrinol Metab 97:4228–4235

    CAS  PubMed  PubMed Central  Google Scholar 

  • Iguchi T, Todoroki R, Yamaguchi S, Takasugi N (1989) Changes in the uterus and vagina of mice treated neonatally with antiestrogens. Acta Anat (Basel) 136:146–154

    CAS  Google Scholar 

  • Jordan VC (2003) Tamoxifen: a most unlikely pioneering medicine. Nat Rev Drug Discov 2:205–213

    CAS  PubMed  Google Scholar 

  • Kan SF, Wang J, Sun GX (2018) Sulforaphane regulates apoptosis- and proliferation-related signaling pathways and synergizes with cisplatin to suppress human ovarian cancer. Int J Mol Med 42(5):2447–2458

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ketani MA, Ketani S, Kaloglu C, Guney B (2002) Effects of tamoxifen administration in rat vaginas: an ultrastructural and light microscopy study. Eur J Gynaecol Oncol 23:557–560

    CAS  PubMed  Google Scholar 

  • Kim NN, Stankovic M, Armagan A, Cushman TT, Goldstein I, Traish AM (2006) Effects of tamoxifen on vaginal blood flow and epithelial morphology in the rat. BMC Women's Health 6:14

    PubMed  PubMed Central  Google Scholar 

  • Konings G, Brentjens L, Delvoux B, Linnanen T, Cornel K, Koskimies P, Bongers M, Kruitwagen R, Xanthoulea S, Romano A (2018) Intracrine regulation of estrogen and other sex steroid levels in endometrium and non-gynecological tissues; pathology, physiology, and drug discovery. Front Pharmacol 9:940

    PubMed  PubMed Central  Google Scholar 

  • Kotrikadze N, Alibegashvili M, Zibzibadze M, Abashidze N, Chigogidze T, Managadze L, Artsivadze K (2008) Activity and content of antioxidant enzymes in prostate tumors. Exp Oncol 30(3):244–247

    CAS  PubMed  Google Scholar 

  • Kumar V, Yadav CS, Datta SK, Singh S, Ahmed RS, Goel S, Gupta S, Mustafa M, Grover RK, Banerjee BD (2011) Association of GSTM1 and GSTT1 polymorphism with lipid peroxidation in benign prostate hyperplasia and prostate cancer: a pilot study. Dis Markers 30(4):163–169

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu CY, Hung MH, Wang DS, Chu PY, Su JC, Teng TH, Huang CT, Chao TT, Wang CY, Shiau CW, Tseng LM, Chen KF (2014) Tamoxifen induces apoptosis through cancerous inhibitor of protein phosphatase 2A-dependent phospho-Akt inactivation in estrogen receptor-negative human breast cancer cells. Breast Cancer Res 16(5):431

    PubMed  PubMed Central  Google Scholar 

  • Mvondo MA, Njamen D, Tanee Fomum S, Wandji J (2012) Effects of alpinumisoflavone and abyssinoneV-4′-methyl ether derived from Erythrina lysistemon (Fabaceae) on the genital tract of ovariectomized female wistar rat. Phytother Res 26:1029–1036

    CAS  PubMed  Google Scholar 

  • Mvondo MA, Njamen D, Tanee Fomum S, Wandji J, Vollmer G (2011) A postmenopause-like model of ovariectomized Wistar rats to identify active principles of Erythrina lysistemon (Fabaceae). Fitoterapia 82:939–949

    CAS  PubMed  Google Scholar 

  • O'Brien JE, Peterson TJ, Tong MH, Lee EJ, Pfaff LE, Hewitt SC, Korach KS, Weiss J, Jameson JL (2006) Estrogen-induced proliferation of uterine epithelial cells is independent of estrogen receptor alpha binding to classical estrogen response elements. J Biol Chem 281(36):26683–26692

    CAS  PubMed  Google Scholar 

  • Ojewole JA, Amabeoku GJ (2006) Anticonvulsant effect of Persea americana Mill (Lauraceae) (Avocado) leaf aqueous extract in mice. Phytother Res 20(8):696–700

    PubMed  Google Scholar 

  • Ojewole J, Kamadyaapa DR, Gondwe MM, Moodley K, Musabayane CT (2007) Cardiovascular effects of Persea americana Mill (Lauraceae) (avocado) aqueous leaf extract in experimental animals. Cardiovasc J S Afr 18(2):69

    CAS  Google Scholar 

  • Padilla-Camberos E, Martínez-Velázquez M, Flores-Fernández JM, Villanueva-Rodríguez S (2013) Ac ute toxicity and genotoxic activity of avocado seed extract (Persea americana Mill., c.v. Hass). Sci World J 10:1–4

    Google Scholar 

  • Paul R, Kulkarni P, Ganesh N (2011) Avocado fruit (Persea americana Mill) exhibits chemo-protective potentiality against cyclophosphamide induced genotoxicity in human lymphocyte culture. J Exp Ther Oncol 9(3):221–230

    PubMed  Google Scholar 

  • Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB (2010) Oxidative stress, inflammation, and cancer: How are they linked? Free Radic Biol Med 49(11):1603–1616

    CAS  PubMed  PubMed Central  Google Scholar 

  • Servais S (2004) Altération mitochondriale et stress oxydant pulmonaire en réponse à l’ozone : effet de l’âge et d’une suplémentation en oméga-3. Thèse de doctorat de l’université Claude Bernard, Lyon 1:17–40

    Google Scholar 

  • Silva FC, Bramatti IC, Toledo AG, Salles FM, Itinose AM, Marek CB (2017) Antihyperglycemic Effect of Quercetin in Ovariectomized Rats Treated with Tamoxifen. J Med Food 20(3):235–242

    CAS  PubMed  Google Scholar 

  • Sinha KA (1972) Colorimetric assay of catalase. Anal Biochem 47:389–394

    CAS  PubMed  Google Scholar 

  • Smith LL, Brown K, Carthew P, Lim CK, Martin EA, Styles J, White IN (2000) Chemoprevention of breast cancer by tamoxifen: risks and opportunities. Crit Rev Toxicol 30:571–594

    CAS  PubMed  Google Scholar 

  • Sosa V, Moliné T, Somoza R, Paciucci R, Kondoh H, Leonart ME (2013) Oxidative stress and cancer: an overview. Ageing Res Rev 12(1):376–390

    CAS  PubMed  Google Scholar 

  • Suri V, Arora A (2015) Management of endometrial cancer: A review. Rev Recent Clin Trials 10(4):309–316

    PubMed  Google Scholar 

  • Takahashi M, Shimomoto T, Miyajima K, Iizuka S, Watanabe T, Yoshida M, Kurokawa Y, Maekawa A (2002) Promotion, but not progression, effects of tamoxifen on uterinecarcinogenesis in mice initiated with N-ethyl-N'-nitro-N-nitrosoguanidine. Carcinogenesis 23:1549–1555

    CAS  PubMed  Google Scholar 

  • Thomson CA, Rock CL, Thompson PA, Caan BJ, Cussler E, Flatt SW, Pierce JP (2011) Vegetable intake is associated with reduced breast cancer recurrence in tamoxifen users: a secondary analysis from the Women's Healthy Eating and Living Study. Breast Cancer Res Treat 125(2):519–527

    CAS  PubMed  Google Scholar 

  • Thomson CA, Sherry Chow HH, Wertheim BC, Roe DJ, Stopeck A, Maskarinec G, Altbach M, Chalasani P, Huang C, Strom MB, Galons JP, Thompson PA (2017) A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen. Breast Cancer Res Treat 165(1):97–107

    CAS  PubMed  PubMed Central  Google Scholar 

  • Udensi UK, Tchounwou PB (2014) Dual effect of oxidative stress on leukemia cancer induction and treatment. J Exp Clin Cancer Res 33:106

    PubMed  PubMed Central  Google Scholar 

  • Udensi UK, Tchounwou PB (2016) Oxidative stress in prostate hyperplasia and carcinogenesis. J Exp Clin Cancer Res 35(1):139

    PubMed  PubMed Central  Google Scholar 

  • Visagie MH, van den Bout I, Joubert AM (2017) A bis-sulphamoylated estradiol derivative induces ROS-dependent cell cycle abnormalities and subsequent apoptosis. PLoS ONE 12(4):e0176006

    PubMed  PubMed Central  Google Scholar 

  • Westwood FR (2008) The female rat reproductive cycle: a practical histological guide to staging. Toxicol Path 36:375–384

    Google Scholar 

  • Wilbur K, Bernhein F, Shapiro O (1949) Determination of lipid peroxydation. Arch Biochem Biophys 24:3959–3964

    Google Scholar 

  • Zhao Y, Li Q, Bagchi IC, Bagchi MK (2010) Estrogen stimulates de novo synthesis of cholesterol in mouse uterus during implantation. Biol Reprod 83:171

    Google Scholar 

  • Zingue S, Magne Nde CB, Clyne C, Njamen D (2014) Elucidation of Underlying Mechanisms by Which Millettia macrophylla Benth induces its estrogenic activity. Int Sch Res Notices 2014:8p

    Google Scholar 

Download references

Acknowledgements

The authors are thankful to the Research Unit of Animal Physiology and Phytopharmacology of the University of Dschang for material support. This research received no specific funding and was performed at the Research Unit of Animal Physiology and Phytopharmacology of the University of Dschang, as part of the employment of the authors.

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Nina-Sonia Messongue Mbollo, Marie Alfrede Mvondo and Dieudonné Njamen. The first draft of the manuscript was written by Marie Alfrede Mvondo and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Marie Alfrede Mvondo.

Ethics declarations

Ethical statement

Animal handling and in vivo experiments were carried out in conformity with the European Union on Animal Care (CEECouncil 86/609) guidelines adopted by the Institutional Ethics Committee of the Cameroon Ministry of Scientific Research and Technology Innovation (Reg. no. FWA-IRD 0001954).

Conflict of interest

Marie Alfrede Mvondo has no conflict of interest. Nina‑Sonia Messongue Mbollo has no conflict of interest. Dieudonné Njamen has no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mvondo, M.A., Messongue Mbollo, NS. & Njamen, D. The ethanol extract of avocado [Persea americana Mill. (Lauraceae)] seeds reduced the hyperplastic effect of tamoxifen on uterine endometrium without changing its effect on the mammary gland. ADV TRADIT MED (ADTM) 21, 305–316 (2021). https://doi.org/10.1007/s13596-020-00443-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13596-020-00443-9

Keywords

Navigation