Chenguang Yao, Ting Tan, Jiangning Yan, Zijia Zhao, Romina Onintsoa Diarimalala, Junjie Wang, William Wang, Hanluo Li, Jingbiao Liu, Yanhong Wei and Kanghong Hu* Pages 1 - 11 ( 11 )
Objective: To develop new Anderson-type polyoxometalates (POMs) with high efficiency and low cytotoxicity, and investigate the effects and mechanisms against lung (A549), cervical (Hela), and breast cancer (MCF7) cell lines.
Methods: Cytotoxicity assessments on Hela, A549, and MCF-7 tumor cells were tested by MTT assay. Antitumor activities of B1 (vanadium-centered, methyl-modified) and B7 (vanadium-centered, hydroxylmodified) were detected by apoptosis, scratch, and colony formation assay. The antitumor molecular mechanisms were explored by western blotting.
Results: This study synthesized and evaluated twelve Anderson-type compounds which were centered with vanadium, chromium, iron, cobalt, nickel, and copper heteroatoms, modified with methyl and hydroxyl at the side chains. Cytotoxicity assessments revealed that compounds B1 and B7 exhibited superior efficacy, with IC50 values of approximately 7 μmol/L of three cell lines. B1 and B7 inhibited proliferation and migration in these cell lines and induced apoptosis in MCF7 and A549 cells. Mechanistic investigations indicated that B1 induces apoptosis in MCF7 cells by inhibiting the AKT signaling pathway and downregulating the expression of apoptosis-related proteins Bcl-2 and Caspase-9.
Conclusion: Novel Anderson-type POMs B1 (vanadium-centered, methyl-modified) and B7 (vanadiumcentered, hydroxyl-modified) exhibited superior efficacy against tumor cells and induced apoptosis via PI3K/ AKT pathway, which provides new theoretical avenues for developing POM-mediated antitumor chemotherapeutic medications.
Antitumor, chemotherapy, polyoxometalate, apoptosis, bioactivity, drug design.