ABSTRACT
OBJECTIVE: Lindqvist-type polyoxometalates (POMs) exhibit potential antitumor activities. This study aimed to examine the effects of Lindqvist-type POMs against breast cancer and the underlying mechanism. METHODS: Using different cancer cell lines, the present study evaluated the antitumor activities of POM analogues that were modified at the body skeleton based on molybdenum-vanadium-centered negative oxygen ion polycondensations with different side strains. Cell colony formation assay, autophagy detection, mitochondrial observation, qRT-PCR, Western blotting, and animal model were used to evaluate the antitumor activities of POMs against breast cancer cells and the related mechanism. RESULTS: MO-4, a Lindqvist-type POM linking a proline at its side strain, was selected for subsequent experiments due to its low half maximal inhibitory concentration in the inhibition of proliferation of breast cancer cells. It was found that MO-4 induced the apoptosis of multiple types of breast cancer cells. Mechanistically, MO-4 activated intracellular mitophagy by elevating mitochondrial reactive oxygen species (ROS) levels and resulting in apoptosis. In vivo, breast tumor growth and distant metastasis were significantly reduced following MO-4 treatment. CONCLUSION: Collectively, the results of the present study demonstrated that the novel Lindqvist-type POM MO-4 may exhibit potential in the treatment of breast cancer.
Subject(s)
Antineoplastic Agents , Apoptosis , Breast Neoplasms , Mitophagy , Reactive Oxygen Species , Tungsten Compounds , Humans , Mitophagy/drug effects , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Breast Neoplasms/genetics , Apoptosis/drug effects , Tungsten Compounds/pharmacology , Animals , Mice , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Reactive Oxygen Species/metabolism , Cell Proliferation/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Xenograft Model Antitumor Assays , Molybdenum/pharmacology , Polyelectrolytes , AnionsABSTRACT
OBJECTIVE: To determine the content of flavonoids in huangqi guizhi wuwu tang (HQGZWWT) of different dosages by uniform design method and analyze their difference for clinical application. METHODS: The uniform design set five factors and 11 levels to explore the content of flavonoids. The results were analyzed by computer with the method of multiple regression analysis. RESULTS: The contribution of each medicinal material to the content of total flavonoids was Radix Astragali (51.8%), Rhizoma Zingiberis (0.967%), Rhizoma Zingiberis (0.689%), Ramulus Cinnamomi (0.381%) and Raidix Paenoiae alba (0.185%), respectively. CONCLUSION: The extraction rate of flavonoids is not directly relative to the total amount of medicines, instead, there is an optimum dosage matching for it.