Table 3.
Proposed Anti-Breast Cancer Mechanisms of Medicinal Plant Extracts or Essential Oils in Preclinical Breast Cancer Models
| Plant Botanical Name | Plant Common Name | Extract/Essential Oil | Cell Models/Animals (Sex) | Mechanisms of Action | References |
|---|---|---|---|---|---|
| Adiantum capillus-veneris | Southern maidenhair fern | Leaf extract | -MCF-7 cell line -BT-47 cell line |
-Modulation of proliferation markers ●↓ PCNA level -Modulation of cell cycle regulators ●↓ Cyclin D1 and CDK4 levels ●↑ p21 level and nuclear relative to cytosolic p21 -Induction of mitochondrial apoptotic pathway ●↑ Bax/Bcl-2 ratio ●↓ ΔΨm ●↑ Caspase-9 and −3 levels ●↑ Cytosolic relative to mitochondrial cytochrome c |
[136] |
| Pteris quadriaurita | Striped brake fern | ||||
| Annona muricata | Soursop, Guanábana, Graviola or Omusitafeli/Ekitafeli | Leaf extract | -Mice bearing 4T1 xenografts (female) | -Regulation of immune system ●↑ White blood cell, T cell and natural killer cell populations -Reduction of inflammation ●↓ NO and MDA |
[151] |
| Leaf extract | -BT-20 cell line | -Suppression of EGFR signalling pathway ●↓ EGFR phosphorylation -Suppression of MAPK signalling pathway ●↓ MAPK phosphorylation -Suppression of PI3K/AKT signalling pathway ●↓ AKT phosphorylation -Suppression of NF-κB signalling pathway ●↓ NF-κB p65 level -Modulation of cell cycle regulators ●↓ Cyclin D1 level |
[153] | ||
| Leaf extract | -MCF-7 cell line | -Stimulation of ROS generation ●↑ Intracellular ROS level -Induction of caspase-dependent apoptosis ●↑ Caspase-3 level |
[154] | ||
| Ipomoea turpethum/Operculina turpethum | Transparent wood rose | Stem extract | -Rats bearing DMBA-induced breast tumours (female) | -Antioxidant activity ●↓ Lipid peroxidation activity ●↑ SOD, CAT, GPx, GSH, vitamin C and vitamin E levels |
[159] |
| Mirabilis jalapa | Four o’clock flower | N/A | -N/A | -N/A | N/A |
| Plectranthus amboinicus | Indian borage | Leaf extract | -MBA-MB-231 cell line | -Induction of caspase-dependent apoptosis ●↑ Caspase-3 and −7 activities |
[171] |
| Punica granatum | Pomegranate | Fruit extract | -MDA-MB-231 cell line -SUM-149 cell line |
-Suppression of NF-κB signalling pathway ●↓ Constitutive NF-κB activity ●↓ NF-κB p50 and p65 levels ●↓ IκBα phosphorylation -Downregulation of Rho GTPases ●↓ RhoA and RhoC levels -Modulation of cellular eicosanoid profile ●MDA-MB-231: ↑ PGE2 and ↓ 15-HETE levels ●SUM-149: ↓ LTB4, 12-HETE and 15-HETE levels |
[184] |
| Peel extract | -MDA-MB-231 cell line | -Modulation of metastasis-related markers ●↑ ICAM-1 level ●↓ MMP-9, fibronectin and VEGF levels |
[185] | ||
| Peel extract | -MDA-MB-231 cell line | -Modulation of EMT markers ●↓ Mesenchymal markers (vimentin and ZEB1) ●↑ Epithelial markers (E-cadherin) -Suppression of β-catenin signalling pathway ●↓ β-catenin level |
[186] | ||
| Fruit extract | -MCF-7 cell line | -Downregulation of DNA repair genes ●↓ MRE11, RAD50, NBS1, RAD51, BRCA1, BRCA2, BRCC3 and MSH6 levels -Induction of DNA double-strand breaks |
[187] | ||
| Fruit extract | -MCF-7 cell line -MDA-MB-231 cell line |
-Anti-estrogenic activity ●↓ Estradiol binding to ER ●↓ ER-mediated gene expression via ERE ●↓ Estrogen responsive gene expression (ERα, pS2 and PR) |
[188] | ||
| Putranjiva roxburghii/Drypetes roxburghii | “Amulet-Plant or Wild Olive or Child-Life-Tree” | N/A | -N/A | -N/A | N/A |
| Zataria multiflora | Avishan-e-Shirazi | Essential oil | -MDA-MB-231 cell line | -Stimulation of ROS generation ●↑ Intracellular ROS level -Intercalation between DNA strands -Induction of DNA damage ●↑ 8-oxoguanine formation ●↑ DNA migration -Induction of mitochondrial apoptotic pathway ●↓ ΔΨm ●↑ Caspase-3 activity |
[198] |
Notes: ↑, increased; ↓, decreased.
Abbreviations: Bax, Bcl-2-associated X protein; Bcl-2, B-cell lymphoma 2; BRCA1/2, Breast cancer gene 1/2; BRCC3, BRCA1/BRCA2-containing complex subunit 3; CAT, catalase; CDK4, cyclin-dependent kinase 4; DMBA, 7,12-dimethylbenz(a)anthracene; DNA, deoxyribonucleic acid; EGFR, epidermal growth factor receptor; EMT, epithelial-mesenchymal transition; ER, estrogen receptor; ERα, estrogen receptor-alpha; ERE, estrogen response element; GPx, glutathione peroxidase; GSH, glutathione; ICAM-1, intercellular adhesion molecule-1; IκBα, inhibitor kappa B-alpha; LTB4, leukotriene B4; MAPK, mitogen-activated protein kinase; MDA, malondialdehyde; MMP-9, matrix metallopeptidase-9; MSH6, MutS homolog 6; NBS1, Nibrin; NF-κB, nuclear factor-kappa B; NO, nitric oxide; PCNA, proliferating cell nuclear antigen; PGE2, prostaglandin E2; PI3K/AKT, phosphoinositide 3-kinase/protein kinase B; PR, progesterone receptor; ROS, reactive oxygen species; SOD, superoxide dismutase; VEGF, vascular endothelial growth factor; ZEB1, zinc finger E-box binding homeobox 1; 12/15-HETE, 12/15-hydroxyeicosatetraenoic acid; ΔΨm, mitochondrial membrane potential.