Table 1 Growth inhibitory effect of curcumin on breast cancer
From: Curcumin: the spicy modulator of breast carcinogenesis
Effect | Curcumin alone or in combination | Model used (*cell line/**animal) | Expression phenotype of the cancer model | Solubilization of curcumin | Mechanism | Reference |
|---|---|---|---|---|---|---|
Suppression of cell proliferation & cell cycle regulation | Curcumin | *MCF7 | ER+ PR+ Her2− | Ethanol. | Inhibits phosphorylation of mTOR and its downstream effector molecule p70S6K and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), | [33] |
Curcumin | *MDA-MB-231 & BT-483 | ER− PR− Her2− | Dimethyl sulphoxide (DMSO) | Down-regulation of NF-kB, cyclin D and MMP-1 transcription | [40] | |
Curcumin | *Breast cancer cells BALB-neuT **BALB/c mice | Cancer cells expressing either high or low levels of ErbB2/neu. | Description not available | Down regulation of ERK1/ERK2 MAP kinases activity; dose dependant manner. | [43] | |
Curcumin +Mitomycin C (MMC) | *MCF-7 **MCF-7 xenograft Female nu/nu athymic mice | ER+ PR+ Her2− | DMSO | p38 MAPK pathway mediated inhibition of cyclin D1, cyclin E, cyclin A, CDK2 & CDK4 with induction of cell cycle inhibitor p21, and p27. | [44] | |
Curcumin | *MCF-7 & MDA-MB-231 | ER+ PR+ Her2− ER− PR− Her2− | DMSO | Inhibit expression of Wnt/β-catenin pathway components: disheveled, beta-catenin, cyclin D1 and slug with alteration of GSK3beta and E-cadherin. | [48] | |
Curcumin | *MCF-7 | ER+ PR+ Her2− | DMSO | Nrf2-mediated down-regulation of Fen1 expression; Nrf2 translocation from the cytoplasm to the nucleus and decrease Fen1 promoter activity by decreasing the recruitment of Nrf2 to the Fen1 promoter. | [51] | |
Apoptosis | Curcumin | *MCF-7 | ER+ PR+ Her2− | Ethanol | Concentration-dependent regulation of genes related to cell death. | [53] |
Curcumin | *MCF 7, MDAH041 (post-crisis cell line from fibbroblasts of patient with LiFraumeni syndrome) & TR9-7 (derived from MDAH041 cells) | ER+ PR+ Her2− MDAH041: the normal p53 allele has been lost during in vivo propagation. TR9-7: express wild-type p53 under control of tetracycline-regulated promoter | Description not available | Increase in p53 level & its DNA-binding activity followed by Bax expression at the protein level | [55] | |
Curcumin | *ENU1564 (originated from an N-ethyl-N nitosourea-induced mammary adenocarcinoma in a female Berlin-Druckrey IV rat) | Â | Description not available | Via intrinsic mitochondrial pathway; increased mitochondrial Ca (2+) and reactive oxygen species production with increased mitochondrial permeability transition. | [57] | |
Curcumin | *MDA-MB-231 | ER− PR− Her2− | DMSO | Dose-dependent inhibition of proliferation; increase Bax to Bcl-2 ratio; increases the protein level of p21 but decreases it for p53 | [58] | |
Curcumin +citral | *MCF 7 | ER+ PR+ Her2− ER− PR− Her2− | Description not available | Cell cycle arrest in G0/G1 phase; induced high levels of reactive oxygen species (ROS) generation and activated p53 and poly (ADP-ribose) polymerase-1 mediated apoptotic pathways. | [59] | |
Curcumin | *MDA-MB-231 | ER− PR− Her2− | Description not available | p53-Notch1 axis mediated downregulation of Notch1 and its downstream target, Hes1 | [65] | |
Curcumin | *MDA468 & HCC1806 | ER− PR− Her2− | Ethanol | Induces double stranded DNA break in cancer cell; promotes phosphorylation of ATM/chk2-specific sites on BRCA1, total expression, and cytoplasmic retention of the BRCA1 protein; BRCA1 is retained in the cytoplasm where it cannot repair DNA damage; activates a DNA damage response in TNBC cells, leading to apoptosis | [68] | |
Curcumin | *MCF-7 | ER+ PR+ Her2− | DMSO | Suppression of IGF-1R gene expression; down-regulate the IGF-1 axis with a decrease in secretion of IGF-1 with a concomitant increase of IGFBP-3 in a dose-dependent manner. | [70] | |
Curcumin | *MCF-7 | ER+ PR+ Her2− | DMSO | Depolymerizes mitotic microtubules, disturbs microtubule-kinetochore attachment and the mitotic spindle structure. Activates the mitotic checkpoint and delays mitotic progression from metaphase to anaphase; p53 dependant apoptosis. | [71] | |
Induction of senescence | Curcumin+ silibin | *T47D | ER positive | DMSO | Decreases human telomerase reverse transcriptase (hTERT) gene expression | [73] |
Curcumin | *Patient-derived primary breast CAF cells (bCAF) | Â | DMSO | p16-dependent, DNA damage independent; without associated inflammatory secretory phenotype | [74] |