The Therapeutic Implications Of Iron Chelator In Hepatocellular Carcinoma And Applications Of Common Dietary Flavonoids In Malaria Treatment

The study of iron chelators as cancer chemotherapeutic agents is still in its infancy. Accordingly, there is a need to optimize new chelating molecules for iron chelation therapy and cancer treatment. So, in this study, several boron-pyrazole derivatives were chosen for the examination of their effects on the proliferation of human hepatocellular carcinoma (HCC) cell lines. The results suggested that potassium tris (4-methyl-l-pyrazolyl) borohydride (KTp4-Me) exhibited the most potent anti-tumor activities among the candidates. Hence, the antiproliferative activity and the iron chelating capacity of the iron chelator KTp4-Me in HCC cell lines HepG2and Hep3B were characterized. KTp4"Me could disrupt cell iron uptake and affect signaling pathways of iron regulation in HCC cell lines and induced the expression of TfRl and HIF-1α in a concentration-dependent manner, which was a typical cell response to iron deficiency. Moreover, KTp4-Me arrested cell cycle in S phase and induced cell apoptosis in both Hep3B and HepG2cells. Overall, our results provide a promising starting point and the possibility of the future development and applications of KTp4-Me in HCC therapy.Dietary flavonoids used as antiplasmodial agents or dietary supplemental agents have several advantages, such as low toxicity to humans, high accumulating concentrations and long half-lives in human plasma. In this study, we investigated the inhibitory effects of a range of common dietary flavonoids on the cysteine protease falcipain-2and aspartic protease plasmepsin II in Plasmodium falciparum. These two proteases have long been considered as important antimalarial drug targets. From the enzyme inhibition assays, we could find that luteolin, kaempferol, myricetin, quercetin, morin and fisetin exhibited high inhibitory potencies on falcipain-2. Noteworthy, myricetin and fisetin also decreased plasmepsin II enzyme activity. Furthermore, myricetin and fisetin were also found to inhibit falcipain-2and plasmepsin II mediated native haemoglobin hydrolysis in a dose dependent manner. Inhibition kinetic investigation and in silico molecular docking studies were also carried out to elucidate structure-activity relationship. In light of these data, here the conclusion is that these compounds appear to constitute interesting chemical scaffolds for further development as antimalarials. The results also broaden the scope of use for dietary flavonoids fisetin and myricetin in the treatment of malaria.