Another biological activity that has been attributed to oleocanthal is the anti-cancer activity.

Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. The last decade many in vitro studies have been applied to investigate the anticancer activity of oleocanthal.

Primary investigations by LeGendre in 2015 showed that OC induced cell death in all cancer cells examined as rapidly as 30 minutes after treatment in the absence of serum. Treatment of non-transformed cells suppressed their proliferation but did not cause cell death and also induced both primary necrotic and apoptotic cell death via induction of lysosomal membrane permeabilization.

There are many possible pathways for the genesis of cancer including over expressions of proteins like mTOR and c-Met.

In 2011 Elnagar tested whether oleocanthal could inhibit the overexpression of c-Met which has an important oncogenic role in many tumors. Oleocanthal inhibited the proliferation, migration, and invasion of the epithelial human breast and prostate cancer cell lines, it demonstrated anti-angiogenic activity and it inhibited the phosphorylation of c-Met kinase.


Fig. c-Met phosphorylation inhibition by various doses of 1 using Z′-LYTE™ assay kit.

The same research team a few years later expanded their research, testing whether oleocanthal could inhibit Dysregulation of the Hepatocyte growth factor (HGF)/c-Met signaling. Results showed that oleocanthal inhibits the growth of human breast cancer cells and also caused a dose-dependent inhibition of HGF-induced cell migration, invasion and G1/S cell cycle progression.

The anticancer activity of oleocanthal in breast cancer cells without affecting nontumoral breast cells was also highlighted by Diez-Bello and his partners in 2019.

There is also well documented evidence that the anticancer activity of oleocanthal is related to the inhibition of the kinase mTor.

Khanfar and his partners examined the possibility that oleocanthal inhibits mTOR which has reported that it has an important role in cancer and Alzheimer’s disease. The authors showed that oleocanthal shared nine out of ten critical binding interactions with a potent dual PIK3-γ/mTOR natural inhibitor which leads in the inhibition of the enzymatic activity of mTOR. Oleocanthal treatment caused a marked down regulation of phosphorylated mTOR in metastatic breast cancer cell line (MDA-MB-231).

Apart from breast cancer, researchers have also investigated the anti-cancer activity in different types of cancer which have similar pathways.

In 2016 Fogli and his partners, tested oleocanthal treatment on in cutaneous malignant melanoma. The researchers investigated the selective in vitro antiproliferative activity of oleocanthal against human malignant melanoma cells. The results showed that oleocanthal had a remarkable and selective activity for human melanoma cells versus normal dermal fibroblasts in low concentration.


A few years later, in 2018 Polini and her research team evaluated the in vitro chemopreventive and anticancer action of EVOO extracts and oil-derived compounds in non-melanoma skin cancer models. Both oleocanthal and oleacein reduced nonmelanoma skin cancer cell viability and migration, prevented colony and spheroid formation, and inhibited proliferation of atypical keratinocytes stimulated with epidermal growth factor. The mechanism beyond this activity was the inhibition of two protein- kinase, Erk and Akt, which are strongly related with melanoma.

Fig. Oleocanthal inhibits MIP1- mRNA expression and protein secretion in ARH-77 cells. (A). Human MIP-1 mRNA expression in ARH77 cells after treatment with OC (10, 25 and 50 M) for 3 hours (B). ARH-77 cells were treated with OC (10, 25 and 50 M) for 3 hours.

Back in 2013, Scotece demonstrated that oleocanthal has a remarkable in vitro activity by inhibiting MIP-1 expression and secretion in multiple myeloma cells. The researcher showed that oleocanthal inhibits myeloma cells proliferation by inducing the activation of apoptosis mechanisms and by down-regulating the same kinases that was mentioned before, ERK1/2 and AKT.

The same period Cusimano and her partners evaluated the potential anticancer effects of oleocanthal in hepatocellular carcinoma (HCC) and colorectal carcinoma (CRC) models. They showed that oleocanthal induced cell growth inhibition in HCC and CRC cells, inhibited colony formation and induced apoptosis in a dose dependentmanner. At the same time oleocanthal was not toxic in primary normal human hepatocytes.

In 2020, Ünsal and his research team published their work on the anti-cancer activity of oleocanthal in neuroblastoma. Their analysis demonstrated that cells were significantly less viable after oleocanthal treatment, inhibited neurite growth in neuroblastoma and prevented growth and proliferation of neuroblastoma cells in culture by increasing oxidative stress and apoptosis.

In another research Pei showed that oleocanthal inhibits proliferation and cell cycle progression and induced apoptosis in human hepatocellular carcinoma cells in vitro. It also suppressed tumor growth in an orthotopic hepatocellular carcinoma cells. model by inhibiting STAT3, a protein which has a crucial role in the genesis of the hepatocellular cancer.