Effect of probiotics and gut microbiota on anti-cancer drugs: Mechanistic perspectives.

Bacteria present in probiotics, particularly the common Lactobacillus and Bifidobacterium microbes, have been found to induce anti-cancer action by enhancing cancer cell apoptosis and protecting against oxidative stress. Probiotics supplements also decrease the cancer-producing microorganism Fusobacterium. Studies have demonstrated that gut microbiota modifies the effect of chemo/radiation therapy. Gut microbes not only enhance the action of chemotherapy drugs but also reduce the side effects of these medications. Additionally, gut microbes reduce immunotherapy toxicity, in particular, the presence of Bacteroidetes or Bifidobacterium decreases the development of colitis by ipilimumab therapy. Probiotics supplements containing Bifidobacterium also reduce chemotherapy-induced mucositis and radiation-induced diarrhea. This review focused on elucidating the mechanism behind the anti-cancer action of Bifidobacterium species. Available studies have revealed Bifidobacterium species decrease cancer cell proliferation via the inhibition of growth factor signaling as well as inducing mitochondrial-mediated apoptosis. Moreover, Bifidobacterium species reduce the adverse effects of chemo/immuno/radiation therapy by inhibiting proinflammatory cytokines. Further clinical studies are needed to identify the powerful and suitable Bifidobacterium strain for the development of adjuvant therapy to support chemo/immuno/radiation therapy.

1-Chromonyl-5-Imidazolylpentadienone Demonstrates Anti-Cancer Action against TNBC and Exhibits Synergism with Paclitaxel.

Curcumin has been well studied for its anti-oxidant, anti-inflammatory, and anti-cancer action. Its potential as a therapy is limited due to its low bioavailability and rapid metabolism. To overcome these challenges, investigators are developing curcumin analogs, nanoparticle formulations, and combining curcumin with other compounds or dietary components. In the present study, we used a 1-chromonyl-5-imidazolylpentadienone named KY-20-22 that contains both the pharmacophore of curcumin and 1,4 benzopyrone (chromone) moiety typical for flavonoids, and also included specific moieties to enhance the bioavailability. When we tested the in vitro effect of KY-20-22 in triple-negative breast cancer (TNBC) cell lines, we found that it decreased the cell survival and colony formation of MDA-MB-231 and MDA-MB-468 cells. An increase in mitochondrial reactive oxygen species was also observed in TNBC cells exposed to KY-20-22. Furthermore, KY-20-22 decreased epithelial-mesenchymal formation (EMT) as evidenced by the modulation of the EMT markers E-cadherin and N-cadherin. Based on the fact that KY-20-22 regulates interleukin-6, a cytokine involved in chemotherapy resistance, we combined it with paclitaxel and found that it synergistically induced anti-proliferative action in TNBC cells. The results from this study suggested that 1-chromonyl-5-imidazolylpentadienone KY-20-22 exhibited anti-cancer action in MDA-MB-231 and MDA-MB-468 cells. Future studies are required to evaluate the anti-cancer ability and bioavailability of KY-20-22 in the TNBC animal model.