Cytotoxic Activity of Oleocanthal Isolated from Virgin Olive Oil on Human Melanoma Cells

Abstract

Oleocanthal is one of the phenolic compounds of extra virgin olive oil with important anti-inflammatory properties. Although its potential anticancer activity has been reported, only limited evidence has been provided in cutaneous malignant melanoma. The present study is aimed at investigating the selective in vitro antiproliferative activity of oleocanthal against human malignant melanoma cells. Since oleocanthal is not commercially available, it was obtained as a pure standard by direct extraction and purification from extra virgin olive oil. Cell viability experiments carried out by WST-1 assay demonstrated that oleocanthal had a remarkable and selective activity for human melanoma cells versus normal dermal fibroblasts with IC50s in the low micromolar range of concentrations. Such an effect was paralleled by a significant inhibition of ERK1/2 and AKT phosphorylation and downregulation of Bcl-2 expression. These findings may suggest that extra virgin olive oil phenolic extract enriched in oleocanthal deserves further investigation in skin cancer.

The olive oil phenolic (-)-oleocanthal modulates estrogen receptor expression in luminal breast cancer in vitro and in vivo and synergizes with tamoxifen treatment

“…In this regard, (−)-oleocanthal can be an appealing option to improve sensitivity to endocrine treatments in luminal breast cancer and reduce the emergence of resistance to hormonal therapies. This is particularly interesting taking into consideration that the antiproliferative effects of (−)-oleocanthal in cancer cell lines are achieved at concentrations that have no or little effect on the viability of non-tumorigenic cells and its exceptionally potent in vivo activities as indicated by multiple previous studies (Akl et al, 2014; Fogli et al, 2016; Pei et al, 2016). …”

“…Earlier studies indicated that (−)-oleocanthal is a potential inhibitor of the hepatocyte growth factor receptor (c-Met) pathway in breast cancer cells (Akl et al, 2014; Elnagar et al, 2011; Mohyeldin et al, 2016b). The antiproliferative effects of (−)-oleocanthal are mediated by inhibiting multiple c-Met downstream signaling molecules including protein kinase B (Akt), mitogen-activated protein kinase (MAPK), signal transducers and activators of transcription-3 (STAT-3), and mammalian target of rapamycin (mTOR) in multiple cancer cells (Akl et al, 2014; Fogli et al, 2016; Khanal et al, 2011; Khanfar et al, 2015; Pei et al, 2016; Scotece et al, 2013). In addition, (−)-oleocanthal induced cancer cell arrest by modulating the expression of cyclins, cyclin-dependent kinases, and arrest proteins (Akl et al, 2014).…”

“…In addition, (−)-oleocanthal induced cancer cell arrest by modulating the expression of cyclins, cyclin-dependent kinases, and arrest proteins (Akl et al, 2014). (−)-Oleocanthal also induced programmed cell death resulting in cytotoxic activity in breast cancer cells characterized by activation of caspases-8 and -3, elevation in cleaved poly (ADP-ribose) polymerase (PARP) levels, and downregulation of Bcl-2 expression (Akl et al, 2014; Fogli et al, 2016; Pei et al, 2016; Scotece et al, 2013). Interestingly, LeGendre et al .…”

“…1) from extra-virgin olive oil (EVOO) known for its anticancer effects both in vitro and in vivo (Akl et al, 2014; Mohyeldin et al, 2016a; Pei et al, 2016). Anticancer activity of (−)-oleocanthal has been demonstrated in different tumor types including breast carcinoma, prostate carcinoma, hepatocellular carcinoma, colon cancer, melanoma, and multiple myeloma (Akl et al, 2014; Elnagar et al, 2011; Fini et al, 2008; Fogli et al, 2016; Pei et al, 2016; Scotece et al, 2013). (−)-Oleocanthal possesses a wide range of anticancer activities including anti-proliferative, anti-migratory, anti-invasive, and anti-angiogenic effects reported among multiple cancer types (Akl et al, 2014; Elnagar et al, 2011; Fini et al, 2008; Fogli et al, 2016; Pei et al, 2016; Scotece et al, 2013).…”

Oleocanthal and oleocanthal-rich olive oils induce lysosomal membrane permeabilization in cancer cells

“…Although several groups have demonstrated oleocanthal’s ability to inhibit key proteins that promote cell growth and survival (12, 14-17, 40), a unifying mechanism for the specific and irreversible cellular death-inducing properties of oleocanthal has not been established. In this report, we observed that a transient exposure of cancer cells to oleocanthal for one hour resulted in the loss of cell viability after 24 hours.…”