Curcumin Sensitizes Chemotherapeutic Drugs Via Modulation of PKC, telomerase, NF-κB and HDAC in Breast Cancer

Abstract

Background: Several tumor markers are overexpressed in breast cancer. Chemotherapy in breast cancer fails due to resistance to chemotherapeutic drugs. A phytochemical such as curcumin can be used in a therapeutic modality as it elicits anti-tumor effects. Methods: Action of curcumin on the expression of several tumor markers, such as protein kinase C, telomerase, NF-κB and histone deacetylase in MCF-7 (ER positive), MDA-MB-231 (ER negative), MCF-12F (control) and also in mice mammary tumors were investigated. Results: Curcumin downregulated the expression of tumor markers both in vitro and in vivo and sensitized tumor cells to the chemotherapeutic drugs cyclophosphamide and paclitaxel. Discussion: Curcumin may be of considerable value in synergistic therapy of cancer such that the drug dose level could be minimized reducing the associated toxicity.

Reversal of Resistance towards Cisplatin by Curcumin in Cervical Cancer Cells

“…Cytotoxic efficacy of cisplatin was determined by the MTT assay (Roy et al, 2011). Cells at a density of 104 were seeded in each of the 96 well plates and exponentially growing cells were treated with curcumin along with cisplatin of different concentrations (indicated in the Figure Legends) for 24 h. Cells treated with TSA (1 µM), a HDAC inhibitor along with cisplatin was considered as positive controls.…”

“…Expressions of HDAC (1 and 2) using specific antibodies were determined in curcumin treated cells by western blot analysis and HDAC activity was measured using assay kit (Roy et al, 2011). Briefly, treated cells were harvested, washed in wash buffer pH 7.5 (HEPES.…”

“…Immunodetection was done by incubating the membrane with primary antibodies overnight at 4 o C with constant shaking followed by washing in TBST and then incubated with alkaline phosphatase conjugated anti-mouse IgG (1:1000 dilutions in TBS) at 4 o C. Protein bands were visualized by treating the membrane with the substrate BCIP/NBT. E6/E7 proteins,acetylated p53,p53,pRb,p21,p27,p73,Cyclin D1,CDK4,MRP1 and Pgp1 Cells cultured in presence and absence of curcumin for 24h were fractionated into nuclear and cytosolic fraction or total cell lysates were prepared following the method of Roy et al, 2011. Total cell lysates or the particulate fractions were separated by SDS-PAGE, transferred to nitrocellulose membranes following the method as described for HDACs.…”

Dietary Phytochemicals as Cancer Preventive Agents: Efficacy and Mechanisms

“…Moreover, curcumin has also been identified as an inhibitor of RTKs. Curcumin inhibits EGF-stimulated tyrosine phosphorylation of EGFR [6,[70][71][72] and decreases the activation of down-stream signaling in cell lines [6,[70][71][72]. A recent report has indicated that curcumin exhibits its anti-tumor effect by regulating miRNAs and the expressions of their target genes [73].…”

“…Numerous studies have reported that curcumin can inhibit NF-κB pathway in various cancer cells, including breast, ovary, prostate, colorectum, and pancreas [65][66][67][68][69]. Curcumin also inhibits the expressions of COX-2 and cyclin D1 [70,71]. Moreover, curcumin has also been identified as an inhibitor of RTKs.…”