Role of curcumin in regulating p53 in breast cancer: an overview of the mechanism of action

Figures & data

Figure 1 Chemical structure of curcumin.

Figure 2 p53 stimulation signals and downstream effects.

Abbreviation: UV, ultraviolet.

Figure 3 The role of curcumin in regulating p53 in BC.

Abbreviation: BC, breast cancer.

Table 1 The effects of curcumin on p53 in vitro: a sample of studies

Cell lines	Tumor inoculation	Curcumin (dose, route)	Response	Reference
MDA-MB-231, epithelial cells of mammary gland; breast, metastatic mammary	LL-15 medium; l-glutamine, 10% FBS and Abs	5 µg/mL, for 48 hours	⇩50–60% inhibition of proliferation ⇩ Cyclin D1 expression ⇧ levels of p21	^Citation126
BT-483, epithelial cells of mammary gland; breast, ductal carcinoma	Dulbecco’s Modified Eagle (DME) medium; l-glutamine, 10% FBS and Abs	5 µg/mL, for 48 hours	⇩60–70% inhibition of proliferation ⇩ CDK-4 expression
T-47D, epithelial cells of mammary gland; breast, DCIS	RPMI-1640 media; l-glutamine, nonessential amino acids, 10% FBS, and Abs	5–80 µM CUR, for 24 hours	⇩20–80 µM of CUR significantly decreases p53 protein levels	^Citation127
EAC, mammary epithelial carcinoma cells	DME or RPMI-1640 medium	10 µM of CUR, for 2 hours	⇩p65NF-κB, NF-κB ⇧p53-p300, Bax, Noxa PUMA ⇩Intrinsic cascade of death	^Citation128
MCF-7, epithelial cells of mammary gland; breast, adenocarcinoma	RPMI-1640 medium	48 hours	⇧ p21, p27 ⇩Cyclin-D1, cyclin-E, cyclin-A, CDK-2, and CDK-4 ⇧Cell cycle arrest	^Citation129
MCF-7, epithelial cells of mammary gland; breast, adenocarcinoma	DM E medium	10 µM of CUR, for 24 hours	⇧Induce apoptosis ⇧p53 levels, Bax ⇧Bcl-xl/Bax ratio ⇩Bcl-2	^Citation91
SK-BR-3 cells, malignant adenocarcinoma of the breast	McCoy’s 5A medium	30 µM of CUR, for 24 hours	⇧Phospho-p53, PPARγ	^Citation130
MCF-7, epithelial cells of mammary gland; breast, adenocarcinoma	DME medium	1 µM of CUR, for 4 days	⇩PTEN, p-AKT, p-MDM2, p53 ⇧Protective effect against bisphenol A, through modulation of miR-19/	^Citation131
MDA-MB-231, metastatic mammary adenocarcinoma	DME medium		PTEN/AKT/p53 axis
MCF-7, epithelial cells of mammary gland; breast, adenocarcinoma	DME medium	40 µM of CUR, for	⇧The number of cells in the early stages of apoptosis, total p53 levels, phospho-Bad (ser112), total Bad levels ⇩Phospho-p53 (ser15)	^Citation132

Note: Abs, antibiotics such as penicillin, streptomycin, and amphotericin B; BT-483, ER-positive BC cell line; MDA-MB-231, ER-negative BC cell line; SK-BR-3, Her-2-positive, ER-negative, PR-negative; T-47D, human BC cell line, positive for both ER and PR.

Abbreviations: Akt, protein kinase B; BC, breast cancer; Bcl-2, B cell lymphoma-2; CDK, cyclin-dependent kinase; CUR, curcumin; DCIS, ductal carcinoma in situ; EAC cells, Ehrlich ascites carcinoma, doxorubicin-resistant cells; ER, estrogen receptor; LL-15 medium, Leibovitz’s L-15 medium; PR, progesterone receptor; PTEN, phosphatase and tensin.

Table 2 The effect of curcumin on animal models bearing malignant breast tumors in vivo: a sample of studies

Animal models	Tumor inoculation	Curcumin (dose, route)	Response	Reference
Female Foxn1^nu/nu mice, 6–8 weeks old	s.c. injection of mba. mb231 cells into the right 10 side flank, 2.5× 6	Diet containing curcumin at 0.6%	⇩ Proliferation of mba.mb231 cells ⇧Apoptosis and p53 expression ⇩Expression of CD-1, PECAM-1 and p65	^Citation133
Swiss albino mice, 23–25 g	i.p. injection of EAC cells, 1 10 × 6	CUR 50 mg/kg body weight	⇩ p65NF-κB, NF-κB ⇧ p53-p300, Bax, Noxa PUMA ⇧Intrinsic cascade of death	^Citation128
Female nu/nu athymic mice, 7 weeks	i.p. of 1.7 mg of 17β -estradiol before inoculation, MCF-7 cells 1×10^7/mL	100 mg/kg of CUR, for 28 days	⇧p21, p27 ⇩Cyclin-D1, cyclin-E, cyclin-A, CDK-2, and CDK-4 ⇧Cell cycle arrest	^Citation129
Female athymic nude mice, orthotopic model	Injection of 2×10^6 of MDA-MB-435LVB cells	Fed with powdered diet containing 2% w/w curcumin	⇧NF-kB, COX-2, and MMP-9	^134
Female BALB/c nude mice, 35–40 days old, 20–22 g, xenograft tumor	s.c. with 2×10^6 MDA-MB-231 cells into the dorsa of each mouse	i.p., 50 µg/kg and 200 µg/kg every other day for 28 days	⇧Apoptosis in a dose-dependent manner, Bax protein levels ⇩Bcl-2 protein levels	^135
Female BALB/c mice weighing about 18–23 g	i.p. of EAT cells, 1×10^5/ animal	i.p. injection, 9.9 µg/mL daily, 10 days	⇧Apoptosis, apoptotic bodies, phosphorylated caspase-3	^136
nu/nu mice, xenografts	s.c. of BT-474, in the flank	8.7 mM/kg of body weight/day, dietary supplementation	⇩Release of cytochrome c by mitochondria, chemotherapy-induced apoptosis, ROS formation, JNK activation	^137
Female BALB/c, 8-week- old mice	100 µL of 4T1 cell suspension	2,000 µg/kg body weight of CUR-encapsulated microspheres, for 30 days	⇩Downregulate p-AKT ⇧ Apoptosis, upregulate p27, upregulate cleaved capspase-3	^138

Note: MDA.MB231, ER-negative BC cell line; MDA-MB-435LVB cells, human BC cells; Noxa, promotes activation of caspases and apoptosis; 4T1, triple-negative BC cells; nu/nu, nude mice.

Abbreviations: BC, breast cancer; Bcl-2, B cell lymphoma-2; COX-2, cyclooxygenase; CUR, curcumin; EAT, Ehrlich ascitic tumor cells; murine mammary adenocarcinoma; i.p., intraperitoneal; JNK, c-Jun NH2-terminal kinase; MMP-9, matrix metalloproteinases 9; NF-kB, nuclear factor kappa B protein; PECAM-1, platelet and endothelial cell adhesion molecule-1; PUMA, p53 upregulated modulator of apoptosis; s.c., subcutaneously; EAC cells, Ehrlich ascites carcinoma, doxorubicinresistant cells.

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