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

Abstract

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.

Recent Advances of Curcumin Derivatives in Breast Cancer

“…It displayed significant antiproliferative activity, enhanced ROS production and a synergistic effect combined with paclitaxel in TNBC cells ( Table 10). [82] …”

“…It displayed significant antiproliferative activity, enhanced ROS production and a synergistic effect combined with paclitaxel in TNBC cells (Table 10). [82] 2.3. exhibited more efficient anticancer activity as well as higher selectivity in MBA-MD-231 and MBA-MD-468 cell lines. Further detailed research indicated that they induced apoptosis and oxidative stress selectively in cancerous cells whereas were almost inactive in normal cells.…”

In vitro Non-Small Cell Lung Cancer Inhibitory Effect by New Diphenylethane Isolated From Stems and Leaves of Dioscorea oppositifolia L. via ERβ-STAT3 Pathway

“…Their reliable source and high safety are the features, which make them the main source of new drug development. Currently, the anti-cancer preparations derived from the plant source account for approximately 32% of the total anti-cancer drugs, such as colchicine, vinblastine, paclitaxel are all isolated from natural products ( Fatima et al, 2019 ; Zhou et al, 2019 ; Modi et al, 2020 ). In the present study, a new diphenylethane compound (D1) was obtained for the first time, its effects on A549 cells were studied, and its possible mechanism of action was explored.…”

Therapeutic vulnerabilities of cancer stem cells and effects of natural products

“…193 In breast cancer, novel analogues are especially promising. [201][202][203] Dimethoxycurcumin (8, Fig. 5) is more stable and signicantly more potent than curcumin in inducing cell death and reducing the clonogenicity of malignant breast cancer cells.…”

“…[201][202][203] In one study, TNBC cells were treated with a molecule built with pharmacophores from both curcumin and chromone, a controller drug normally used as therapy as an alternative to glucocorticoids and here used to increase bioavailability. 202 This novel molecular combination decreases cell survival and colony formation, increases mitochondrial reactive oxygen species, and decreases EMT. When co-treated with paclitaxel, the treatment synergistically induces anti-proliferative action in TNBC cells.…”