TABLE 2.
Reported synergetic effects of a combination of inhibiting tumor growth, inhibiting proliferation, or inducing apoptosis.
| Herb/formulations | Evidence | Dosage of tamoxifen | Dosage of herb | Effects | Suggested mechanism |
|---|---|---|---|---|---|
| Genistein | BT-474 cell lines (Mai et al., 2007) | 5 μM | 25 μM | Inhibit cell growth and apoptosis | Downregulate survivin, HER1, HER2, HER3, and ER-α expression |
| Z-Ligustilide | MDA-MB-231 cell lines (Ma et al., 2017) | 5 μM | 50 μM | Induce apoptosis and S and G2/M phases cell cycle arrest | Downregulate cyclin A, cyclin E, CDK1, and CDK2 levels, upregulate p21, p27, MTA1 levels, reactive the ERα expression, and transcriptional activity |
| SCS | MCF-7, MDA-MB-231 cell lines (Yaacob et al., 2014) | 2.5, 5 μM | 8.5 or 10.0 μg/ml | Inhibit proliferation, increase apoptosis | Modulate mitochondrial membrane and active caspase-8 and caspase-9 |
| GTE | MCF-7, ZR75, and T47D cell lines (Sartippour et al., 2006) | 5–10 μg/ml | 0.2–40 μg/ml | Inhibit proliferation, increase apoptosis | Decrease level of ER-α, inhibit the stimulation of p44/42 MAPK activity |
| Viscum album L. | MCF-7 cell line (Weissenstein et al., 2019) | 1 μM endoxifen | 10 μg/ml | Inhibit proliferation, increase apoptosis, and induce cell cycle arrest | - |
| FE | MDA-MB-231 and MCF-7 cell lines (Zhang et al., 2013) | 10 μM | 200 μg/ml | Enhance cytotoxicity, Synergistic Induce apoptosis and cell cycle arrest |
Downregulate the expression of BCL-xl and Mcl-1, upregulate the expression of BAX, modulate ERK and AKT phosphorylation, increase ROS level, and reduce GSH level |
| Trifolium pratense | MCF-7 and MDA-MB-231 cell lines (Vlaisavljevic et al., 2014) | 1.55–24.88 μM, MCF-7 cell; 11–176 μM, MDA-231 cell | 142–2272 μg/ml, MCF-7 cell; 210.5–3368 μg/ml, MDA-231 cell | Increase cytotoxic effect | - |
| BreastDefend | MCF-7 cell lines (Cheng et al., 2017) | 1 μM 4-OHT | 10 μg/ml | Inhibit proliferation and induce apoptosis | Upregulate c-PARP, BRAF, p21mRNA levels, downregulate FN1 Bcl-2 mRNA levels |
| Huaier | BALB/c nu/nu female mice (Qi et al., 2016) | 5 mg/kg i.g. | 0.5 mg/μl i.g. | Reduce tumorigenesis and metastasis | Upregulate Bax, Beclin-1, Lc3b, and downregulate Bcl-2, Cyclin D1 level |
| GTE | Ovariectomized nude mice (Sartippour et al., 2006) | 20 mg pellet, subcutaneously inoculated | 2.5 g/l in drinking water | Inhibit tumor growth, suppress angiogenesis, increase larger areas of necrosis and lower tumor blood vessel density | Decrease level of ER-α |
| C3H/OuJ mice (Sakata et al., 2011) | 10 mg pellet, subcutaneously inoculated | 0.1 or 1% in drinking water | Decrease the tumor incidence and AgNOR counts | - | |
| BreastDefend | Nu/Nu immune-compromised female ovariectomized mice (Cheng et al., 2017) | 5 mg/pellet, subcutaneously inoculated | 100 mg/kg i.g. | Inhibit tumor growth, enhance apoptosis | Increase apoptotic bodies, upregulate expressions of BRAF and p21, downregulate pro-apoptotic Bcl-2 protein |