Realizing the Potential of Blueberry as Natural Inhibitor of Metastasis and Powerful Apoptosis Inducer: Tapping the Treasure Trove for Effective Regulation of Cell Signaling Pathways

Blueberries belong to the genus Vaccinium of the family Ericaceae. Rapidly accumulating experimentally verified data is uncovering the tremendous pharmacological properties of biologically active constituents of blueberries against different diseases. Our rapidly evolving knowledge about the multifaceted nature of cancer has opened new horizons to search for different strategies to target multiple effectors of oncogenic networks to effectively inhibit cancer onset and progression. Excitingly, whole blueberry powder and various bioactive constituents (pterostilbene, malvidin-3-galactoside) of blueberries have been shown to efficiently inhibit metastasis in animal models. These results are encouraging and future studies must focus on the identification of cell signaling pathways effectively modulated by blueberries in different cancers. It seems exciting to note that researchers are focusing on metastasis inhibitory effects of blueberry; however, to reap full benefits, it is necessary to take a step back and critically re-interpret the mechanisms used by active components of blueberry to inhibit or prevent metastasis. JAK/STAT, TGF/SMAD, Notch, SHH/GLI, and Wnt/ β-Catenin have been shown to be directly involved in the regulation of metastasis. However, because of limited studies, it is difficult to critically assess the true potential of blueberry. Loss of apoptosis, metastasis and deregulation of signaling pathways are branching trajectories of molecular oncology. Accordingly, we have to emphasize on these essential facets to realistically claim blueberry as "Superfood". Different clinical trials have been conducted to gather clinical evidence about the chemopreventive role of blueberry or its bioactive components in cancer patients. But it seems clear that because of the lack of sufficient proof-of-concept studies, we cannot extract significant information about the transition of blueberry into the next phases of clinical trials. Overview of the existing scientific evidence revealed visible knowledge gaps and a better understanding of the targets of blueberry will be helpful in efficient and meaningful translation of laboratory findings to clinically effective therapeutics.