Antiproliferative effect of an analog of curcumin bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione in human breast cancer cells.

Abstract

BACKGROUND AND OBJECTIVES:

Curcumin exhibits growth-suppressive activity against a variety of cancer cells, but low bioavailability prevents its use in chemotherapeutic applications. One strategy for circumventing this problem has been the creation of synthetic analogs. In this study we synthesized an analog of curcumin bis-1,7-2(hydroxyphenil)-hepta-1,6diene-3,5diore (BDMC-A) and investigated its anti-breast cancer property.

MATERIALS AND METHODS:

We compared the impact of bis-1,7-2(hydroxyphenil)-hepta-1,6diene-3,5diore (BDMC-A) with that of curcumin in human breast cancer cell line MCF-7. MTT [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide] cell viability assay was used to examine the cell viability/proliferation. LDH assay and cell counts were performed to assess the cytotoxicity and anti-proliferative effects of the compound respectively. Flow cytometry followed by Western blot were performed to investigate the cell cycle distribution.

RESULTS:

BDMC-A has an inhibitory effect on MCF-7 cells comparably equivalent to that of curcumin as determined by MTT assay. Cytotoxicity of the cells by both curcumin and BDMC-A were confirmed by LDH release assay and cell count assay. Flow cytometric studies showed accumulation of cells in the G2/M phase which confirms the cell cycle arrest. This was further confirmed by immunoblotting of the protein Cyclin D1, whose expression were found to be decreased in both curcumin and BDMC-A treatment.

CONCLUSIONS:

The results indicate that the curcumin analog exhibit potent inhibitory activity which is comparable to that of curcumin in human breast cancer cells. Since the solubility of BDMC-A was higher in aqueous medium, it is expected to be more bioavailable, and hence more active in vivo. Further evaluation might reveal its role on various molecular targets.

• Authors: M Kumaravel, P Sankar, R Rukkumani
• Journal: European review for medical and pharmacological sciences (Eur Rev Med Pharmacol Sci) Vol. 16 Issue 14 Pg. 1900-7 (Dec 2012) ISSN: 1128-3602 [Print] Italy
• PMID: 23242714 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Biomarkers, Tumor
• CCND1 protein, human
• bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione
• Cyclin D1
• L-Lactate Dehydrogenase
• Curcumin

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Biomarkers, Tumor (metabolism)
• Blotting, Western
• Breast Neoplasms (enzymology, pathology)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Curcumin (analogs & derivatives, pharmacology)
• Cyclin D1 (metabolism)
• Dose-Response Relationship, Drug
• Female
• Flow Cytometry
• G2 Phase Cell Cycle Checkpoints (drug effects)
• Humans
• L-Lactate Dehydrogenase (metabolism)
• MCF-7 Cells
• Time Factors