Apoptosis‐inducing effect of garcinol is mediated by NF‐κB signaling in breast cancer cells

Abstract

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.

Garcinol, a Polyisoprenylated Benzophenone Modulates Multiple Proinflammatory Signaling Cascades Leading to the Suppression of Growth and Survival of Head and Neck Carcinoma

“…Although garcinol has been shown to inhibit the constitutive NF-kB activation in different tumor cell lines (14,37), but its effect on NF-kB signaling in HNSCC cell lines remains largely unexplored. We first found that NF-kB is constitutively active in HNSCC cells, but the exact reason, why it is persistently active in CAL27 cells is still not clear.…”

“…Garcinol has gained much attention in the field of cancer research in recent years, and several reports have shown the antineoplastic and chemopreventive role of garcinol in different cancers, such as leukemia, colorectal, gastrointestinal, and breast cancers (12)(13)(14)(15)(16). Although there is a prior evidence showing that garcinol can inhibit 4-nitroquinoloine 1-oxide-induced tongue carcinogenesis (17), mechanisms through which garcinol elicits its antitumor activity, specifically in HNSCC, is unknown till date.…”

Therapeutic nanomedicine surmounts the limitations of pharmacotherapy

“…Common anti-cancer agents have a poor biodistribution, and poor pharmacokinetics, creating adverse effects on healthy tissues [82]. By identifying disease biomarkers such as a protein, mutant gene, lipid, carbohydrate RNA, or small metabolites, targeted treatments can be designed using multifunctional nanoparticles that are able to detect and image tumours [83]. Some of the nanobased anti-cancer drugs currently used to treat various forms of cancer are reported in table 5.…”

“…The first sets of nanoparticles used for cancer treatment were biodegradable and biocompatible liposomes capable of carrying both hydrophobic and hydrophilic molecules [86]. They consist of a lipid bilayer surrounding an aqueous core, encapsulating the drug [83], highly endowed with the ability to permeate cell membranes easily to bind to DNA or RNA for transfection [86]. Dendrimers are also used for a range of therapeutics and diagnostics by carrying drugs either by encapsulation or conjugation in cancer, and in photodynamic therapy and hyperthermia therapies using AuNPs.…”

Isolation and biological activity of compounds fromGarcinia preussii

“…In Ivory Coast, the leaves are taken as a decoction to relieve tooth pain (Visser, 1975). Previous phytochemical studies indicated that mostly xanthones (Kuete et al, 2007a), benzophenones (Ahmad et al, 2010), triterpenes (Chung et al, 1998), flavonoids, and biflavonoids (Iwu & Igboko, 1982) were found in the genus Garcinia and they exhibited antioxidant, antimicrobial, antiinflammatory, and antitumor activities (Hay et al, 2004).…”