Intravenuous but not oral simultaneous use of Pterostilbene and Quercetin Inhibits Melanoma

A new study aiming to improve on the results with Resveratrol found that the joint use of Pterostilbene and Quercetin inhibits metastatic melanoma growth and extends host survival when administered intravenously but not orally. It shows both the potential of the compounds as well as limitations to oral supplementation to combat a highly malignant tumor.

It should be noted here that the researchers do not rule out in general possible benefits of using oral administration because doses required to inhibit metastatic growth may depend on the cell type. Also Pterostilbene and Quercetin could be useful in other oxidative stress-related pathologies (e.g., diabetes, arteriosclerosis, neurodegenerative diseases, or ischemic heart) where doses required to obtain benefits could be similar or entirely different.

Different phenolic compounds, like resveratrol, show potent antioxidant effects and may have therapeutic applications in oxidative stress-related diseases such as cancer. The mechanisms by which resveratrol exerts its antitumor effects are suggested to be inhibition of certain enzymes for example ribonucleotide reductase, DNA polymerase, protein kinase or cyclooxygenase or then the inhibition of reactive oxygen species-mediated carcinogenesis, cell proliferation and apoptotic cell death activation. Unfortunately resveratrol has a very low bioavailability which limits its potential.

Pterostilbene and quercetin, two structurally related and also naturally occurring small polyphenols, show much longer half-life in vivo.

Pterostilbene is about 60 to 100 times stronger as an antifungal agent and shows similar anti cancer properties as Resveratrol. Similarly research in Quercetin  has confirmed that it also exhibits antitumor properties, likely due to immune stimulation, free radical scavenging, alteration of the mitotic cycle in tumor cells, gene expression modification, antiangiogenesis activity, apoptosis induction or a combination of these effects. It should also be noted that Quercitin is one of the flavonoids most potent antioxidants because it shows all of the following structural elements that cause the anti-oxidant effect: an o-diphenolic group, two to three double bonds conjugated with the 4-oxo function, and OH groups in positions 3 and 5. The reasearchers experimented in-vitro with different combinations of the phenolic compounds on cell growth and concluded the combination of Pterostilbene and quercetin works best (see the figure above the article).

Untill now the potential anticancer effect induced by natural polyphenols has however still not been proven effective by systemic administration. In this study the researchers investigated the anticancer properties of Pterostilbene and Quercetin in bioavailable concentrations.

The study showed that bioavailable concentrations of Pterostilbene and Quercetin, measured in plasma after oral administration, failed to inhibit B16M-F10 cell growth. However, bioavailable concentrations of Pterostilbene and Quercetin, measured in plasma after intravenous administration, inhibited tumor growth up to ∼ 56% (even when both polyphenols were present only for 60 minutes for each 24 hours of culture) without increasing the rate of cell death (cell viability remained > 95%, as in controls, in all cases). These experimental facts suggest that Pterostilbene and Quercetin may act as rapid molecular signals interfering, in a concentration-dependent fashion, in the mechanism of cell division.

To show that  Pterostilbene and Quercetin, inhibit in vivo metastatic growth of a highly malignant tumor leading to longer host survival, the researchers used daily intravenous administration in mice of high doses (20 mg/kg body weight administered once a day).  The result was inhibition of  (73%) metastatic growth of B16M-F10 cells in the liver, a common site for metastasis development. The findings demonstrated that the association of PTER and QUER inhibits metastatic melanoma growth and extends host survival.

You can find the study here.

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