Apoptosis-inducing effect of garcinol is mediated by NF-kappaB signaling in breast cancer cells.
Garcinol, obtained from Garcinia indica in tropical regions, is used for its numerous biological effects. Its anti-cancer activity has been suggested but the mechanism of action has not been studied in-detail, especially there is no report on its action against breast cancer cells. Here we tested our hypothesis that garcinol may act as an anti-proliferative and apoptosis-inducing agent against breast cancer cell lines. Using multiple techniques such as MTT, Histone-DNA ELISA, Annexin V-PI staining, Western blot for activated caspases and cleaved PARP, homogenous caspase-3/7 fluorometric assay and EMSA, we investigated the mechanism of apoptosis-inducing effect of garcinol in ER-positive MCF-7 and ER-negative MDA-MB-231 cells. We found that garcinol exhibits dose-dependent cancer cell-specific growth inhibition in both the cell lines with a concomitant induction of apoptosis, and has no effect on non-tumorigenic MCF-10A cells. Our results suggested induction of caspase-mediated apoptosis in highly metastatic MDA-MB-231 cells by garcinol. Down-regulation of NF-kappaB signaling pathway was observed to be the mechanism of apoptosis-induction. Garcinol inhibited constitutive NF-kappaB activity, which was consistent with down-regulation of NF-kappaB-regulated genes. This is the first report on anti-proliferative and apoptosis-inducing action of garcinol against human breast cancer cells and the results suggest that this natural compound merits investigation as a potential chemo-preventive/-therapeutic agent, especially against breast cancer.
Ahmad
Aamir
A
Department of Pathology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Center, Detroit, MI 48201, USA.
Wang
Zhiwei
Z
Ali
Raza
R
Maitah
Ma'in Y
MY
Kong
Dejuan
D
Banerjee
Sanjeev
S
Padhye
Subhash
S
Sarkar
Fazlul H
FH
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D013729:Terpenes / Q000494:pharmacology* / Q000627:therapeutic use*
D016328:NF-kappa B; D013729:Terpenes; C054597:garcinol