Anethole suppressed cell survival and induced apoptosis in human breast cancer cells independent of estrogen receptor status
Introduction
Asian women have a significantly lower risk of developing breast cancer, believed to be at least in part due to diet and lifestyle. Star anise is a spice that has been used in many traditional Chinese medicines to reduce inflammatory symptoms. Anethole, 1-methoxy-4-(1-propenyl) benzene, is the principle aromatic compound found in star anise. For the past decade, numerous studies have been conducted with anethole and its analogs to uncover the potential anti-cancer effects in natural spices. One of anethole's derivatives, anethole ditholethione (ADT), has been shown to have anti-inflammatory properties that are competent in increasing intracellular levels of glutathione (GSH) and gluthione-S-transferase (GST) (Stohs et al. 1986) and in a phase II trial significantly reduced the lung cancer progression in smokers (Lam et al. 2002). Two other derivatives eugenol and isoeugenol inhibit lipid peroxidation and reduce oxidative levels by scavenging hydroxyl radicals (Taira et al. 1992). Anethole trithione significantly inhibits mammary cancer multiplicity in DMBA-induced rat mammary cancer models (Lubet et al. 1997) and azoxymethane-induced colon carcinogenesis (Reddy et al. 1993). However, several studies have suggested that anethole might not be an effective anti-cancer agent due to its estrogenic properties (Tabanca et al. 2004) and the proliferation promoting properties of its metabolite 4-hydroxy-1-propenylbenzene (4OHPB) (Nakagawa et al. 2003). In order to resolve this discrepancy, we proposed to evaluate the effect of anethole on several physiological parameters of human breast cancer cells in vitro and at the same time continue to delineate the mechanisms through which anethole might mediate its anti-inflammatory effects in the context of estrogen receptor involvement.
Section snippets
Cell lines and reagent
MCF-7 and MDA-MB-231 breast cancer cells were obtained from the American Type Culture Collection and maintained in Improved Minimal Essential Medium (Life Technologies Inc., Gaithersburg, MD) supplemented with 10% Fetal Bovine Serum (FBS) (Sigma, St. Louis, MO) and 6 ng/ml bovine insulin (Sigma). Trans-anethole was purchased from Sigma–Aldrich at 99% purity (cat no. 117870) and dissolved in DMSO to obtain a stock solution of 1 M.
Survival assay
Cell survival was assessed by colony formation assay. Cells were
Repression of survival in both estrogen receptor (ER) positive and ER negative cell lines
Discordance in the literature that investigates the chemopreventive efficacy of anethole and its contradicting estrogenic activity Derivatives of anethole have demonstrated anethole might act as a growth promoting or growth inhibitory compound, we were interested in the effect To determine whether trans-anethole has any impact on the cell survival, we conducted clonogenic assays using MCF-7 and MDA-MB-231 in which cell were treated with increasing (1 × 10−6–1 × 10−3 M) concentrations of anethole for
Discussion
The investigation of the anti-cancer effects anethole may mediate commences with the physiological assays of cell survival and cell proliferation. Initial assessment has found both negative and positive results in which anethole has failed to induce repression of cell proliferation when MCF-7 and MDA-MB-231 cells were incubated with 10−6–10−3 M of trans-anethole dissolved in DMSO for 94 h at 37 °C (Fig. 2A and B). However, in a colony formation assay, the identical concentrations have reduced, in
Acknowledgments
We thank Dr. George Mitchell from the University Co-operative Society in University of Texas at Austin for granting this project an Undergraduate Research Fellowship.
References (7)
- et al.
Cytotoxic and xenoestrogenic effects via biotransformation of trans-anethole on isolated rate hepatocytes and cultured MCF-7 human breast cancer cells
Biochem. Pharmacol.
(2003) - et al.
Effects of oltipraz, BHA, ADT and cabbage on glutathione metabolism, DNA damage and lipid peroxidation in old mice
Mech. Ageing Dev.
(1986) - et al.
A randomized phase IIb trial of anethole dithiolethione in smokers with bronchial dysplasia
J. Natl. Cancer Inst.
(2002)
Cited by (56)
SPME and solvent-based GC–MS metabolite profiling of Egyptian marketed Saussurea costus (Falc.) Lipsch. concerning its anticancer activity
2022, Phytomedicine PlusCitation Excerpt :In the same context, anethole decreased prostate cancer metastasis (DU145) cell line through upregulation of phosphatase and tensin homolog that inhibited the Akt pathway (Rhee et al., 2014). Anethole also successfully induced apoptosis of the prostate (Elkady, 2018), breast (Chen and DeGraffenried, 2012), and oral cancer cell lines (Contant et al., 2021). COS is another bioactive constituent of S. costus-induced apoptosis through B-cell lymphoma 2 downregulation of human leukemia cells (Li et al., 2020), colon and breast cancer cell lines (El-Far et al., 2021a, 2021).
Anethole inhibits RANKL-induced osteoclastogenesis by downregulating ERK/AKT signaling and prevents ovariectomy-induced bone loss in vivo
2021, International ImmunopharmacologyPimpinella anisum and female disorders: A review
2021, Phytomedicine PlusVolatile oil of Croton zehntneri per oral sub-acute treatment offers small toxicity: perspective of therapeutic use
2019, Revista Brasileira de Farmacognosia