Spices and culinary herbs for the prevention and treatment of breast cancer: A comprehensive review with mechanistic insights

Abstract

Breast cancer (BC) continues to be the primary malignant neoplasm affecting women. For many years, traditional approaches such as chemotherapy, hormone therapy, radiation, and surgical interventions have been employed to treat BC. However, these therapies often fall short due to considerable adverse effects and the development of multidrug resistance or tolerance. Spices and culinary herbs that have been utilized in culinary practices for millennia have also demonstrated therapeutic effects in traditional medicinal practices serving to both prevent and treat BC. This review aims to comprehensively explore the roles and underlying mechanisms through which spices and culinary herbs exert anti-BC properties. These natural ingredients exhibit diverse anti-BC effects that encompass diverse mechanisms, including the inhibition of BC cell proliferation, migration, metastasis, and angiogenesis, as well as the induction of cell cycle arrest and apoptosis. These actions are achieved by targeting signaling pathways such as phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), notch signaling, Hedgehog signaling, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and Wingless/int (Wnt)/β-catenin signaling pathways that are predominantly overexpressed in breast tumors or are exploited by them to promote cancer progression. Additionally, compounds such as curcumin, allicin, gingerol, zerumbone, diosgenin, capsaicin, piperine, quercetin, malabaricone C, eugenol, cardamomin, carnosol, cinnamaldehyde, sinigrin present in these spices and herbs may be more effective with reduced side effects against BC compared to conventional chemotherapeutic drugs. This review presents a concise overview of the potential contributions of spices, culinary herbs, and their potent bioactive constituents against BC, with particular emphasis on elucidating their mechanisms of action.

Keywords: Antineoplastic agents; Breast cancer; Complementary therapies; Phytochemicals; Spice.

Graphical abstract

Figure 1

Chemical structures of compounds (1–23) derived from spices and culinary herbs demonstrate efficacy against breast cancer.

Figure 2

Chemical structures of compounds (24–37) derived from spices and culinary herbs demonstrate efficacy against breast cancer.

Figure 3

A simple representation showing the mechanisms of anti-breast cancer effects of Curcuma longa and its major bioactive compound, curcumin. C. longa extract caused caspase-3-induced apoptosis by increasing p53 gene expression and decreasing survivin protein expression. Both the extract and its active constituent curcumin inhibit telomerase activity and prevent cell growth in the S and G2/M phases of the cell cycle. Curcumin showed IGF-1 induced apoptosis by lowering IGF-1 in breast cancer cells. It also induced apoptosis through the p53-p21 pathway and enhanced BRCA1 protein expression which resulted in DNA damage and cell apoptosis. By decreasing fatty acid synthase, it triggered apoptosis. Again, it downregulated angiogenesis by lowering the VEGF, COX-2, and MMP-9 expressions. Through decreasing β-catenin and cyclin D1 protein expressions in the β-catenin pathway, curcumin showed G2/M arrest in breast cancer cells. BRCA1: Breast cancer gene 1; CDK: Cyclin-dependent kinase; COX-2: Cyclooxygenase-2; Cyt-C: Cytochrome c; FAS: Fatty acid synthase; Fz: Frizzled; G1: Gap 1; G2: Gap 2; hTERT: Human telomerase reverse transcriptase; IGF-1: Insulin-like growth factor-1; M: Mitosis; MMP: Matrix metalloproteinase; VEGF: Vascular endothelial growth factor; S: Synthesis; Wnt: Wingless/int.

Figure 4

Potential molecular mechanism of the anti-breast cancer effects of bioactive compounds of Allium sativum. Diallyl disulfide and S-allyl mercaptocysteine both activated the caspases by increasing BAX and decreasing Bcl-X_L proteins. Diallyl disulfide downregulated MMP-9 and blocked the β-catenin pathway, resulting in cell apoptosis. Diallyl trisulfide activated the JNK pathway by increasing the levels of FAS, cyclin D1, BAX, and P53 proteins. Finally, C-jun was phosphorylated and produced intracellular ROS which led the cell to undergo apoptosis. Allicin blocked the ERK_1/2 and NF-κB signaling pathways which inhibited the TNF-α-mediated induction of VCAM-1 which finally suppressed the invasion and metastasis of the breast cancer cell lines. S-allyl mercaptocysteine triggered the mitochondrial apoptotic pathway by caspase activation which potentially stimulated cell apoptosis. Bcl-X_L: B cell lymphoma-extra large; BAX: Bcl-2-associated X protein; ERK: Extracellular signal-regulated kinase; FAS: Fatty acid synthase; G1: Gap 1; NF- κB: Nuclear factor kappa-light-chain-enhancer of activated B cells; JNK: c-Jun N-terminal kinase; MMP-9: Matrix metalloproteinase; TNF: Tumor necrosis factor; VCAM-1: Vascular cell adhesion molecule 1.

Figure 5

Effects of ginger's major bioactive compounds on breast cancer. 6-Gingerol and 6-shogaol induced apoptosis through the downregulated hTERT and mTOR pathways. 6-gingerol and gingerenone A decreased cell invasion by raising ROS levels, zerumbone inhibited the formation of osteoclasts by RANKL-induced activation of NF-κB and reduced cell invasion by blocking the CXCL12/CXCR4 pathway, dihydrocapsaicin and 10-gingerol enhanced caspase activity and disrupts phosphorylation-dependent signaling pathway such as PI3K/AKT/mTOR effectively inhibiting cellular proliferation and inducing apoptosis. ADRB2: Adrenoceptor beta 2; AKT: Protein kinase B; BAX: Bcl-2-associated X protein; CASP: Caspase; CXCL12: C–X–C motif chemokine 12; CXCR4: C–X–C chemokine receptor type 4; hTERT: Human telomerase reverse transcriptase; MMP: Matrix metalloproteinase; mTOR: Mammalian target of rapamycin; NF-κB: Nuclear factor kappa-light-chain-enhancer of activated B cells; PI3K: Phosphoinositide 3-kinase; RANKL: Receptor activator of nuclear factor kappa-Β ligand; ROS: Reactive oxygen species.

Figure 6

Mechanism of action of clove bud in breast cancer. It induced apoptosis through increasing cell cycle arrest via increasing phosphorylation of ATM, HA2.X, Erk, p38MAPK, JNK, p53, SMC, BAX, and Caspase protein. It also inhibited angiogenesis and cancer stem cells via decreasing VEGFA and CD24/CD44 respectively. ALDH1: Aldehyde dehydrogenase 1; ATM: Ataxia telangiectasia-mutated; BAX: Bcl-2-associated X protein; Bcl-2: B-cell lymphoma 2; CD: Cluster of differentiation; Erk: Extracellular signal-regulated kinase; JNK: c-Jun N-terminal kinase; p38MAPK: p38-mitogen-activated protein kinase; ROS: Reactive oxygen species; SMC: Structural maintenance of chromosomes 1; VEGFA: Vascular endothelial growth factor A.