Calcicoptosis Induced by Purple Sweet Potato Anthocyanins through the Nonosmotic Regulation of the NFAT5/S100A4‐S100A9 Pathway in Acute Lymphoblastic Leukemia

Abstract

Purple sweet potato is considered an abundant, inexpensive, and ideal source of anthocyanins. Purple sweet potato anthocyanins (PSPAs) have been shown to possess high antimutagenicity and antitumor effects due to the abundance of acylated anthocyanins. However, the effect and underlying mechanism of PSPA effects in acute lymphoblastic leukemia (ALL), especially T-cell acute lymphoblastic leukemia (T-ALL), remain unclear. In this study, the antileukemic effects of PSPAs and the underlying molecular mechanisms were evaluated by in vitro and in silico assays. PSPAs extracted from ten cultivars were analyzed and quantified. Anthocyanins from Nanzi 018, which showed the best antileukemic effect, were selected to analyze the underlying mechanism. First, the PSPAs potently reduced cell viability and induced apoptosis. Additionally, the PSPAs sharply increased intracellular Ca 2 + levels, which resulted in calcium overload in T-ALL cells. Furthermore, on the basis of bioinformatics analyses, we focused on an osmotically regulated transcription factor, NFAT5. Molecular docking preliminarily indicated that PSPA molecules bound and interacted with the NFAT5 protein. Western blot analyses confirmed that PSPAs elicited calcium overload by nonosmotic regulation of NFAT5/S100A4-S100A9 pathway activation. Moreover, pretreatment with a NFAT5 inducer confirmed that PSPAs targeted NFAT5 and affected p38/NF-кB/Bcl-2/Caspase-3 axis activation. This study demonstrates that PSPAs exert their antileukemic effects through calcicoptosis induction by targeting NFAT5.

Integrating natural compounds and nanoparticle‐based drug delivery systems: A novel strategy for enhanced efficacy and selectivity in cancer therapy

“…31 Various research shows that anthocyanins have preventive and therapeutic properties against different cancers. In general, fruits and vegetables containing the natural pigment of anthocyanin have been accepted as preventive agents for colon cancer, 32 liver cancer, 33 breast cancer, 34 prostate cancer, 35 leukemia, 36 lung cancer, 37 and skin cancer. 38 Since anthocyanins are sensitive to environmental conditions, the biological activity of anthocyanins is significantly reduced during intestinal digestion.…”

Evaluation of the Potential of Duckweed as a Human Food, Bioethanol Production Feedstock, and Antileukaemia Drug

“…Subsequently, the membranes were incubated with the primary antibodies at 4 °C overnight. After three washes with PBST, the membranes were incubated with the secondary antibodies at RT for 1 h. Finally, the proteins were visualized by an enhanced chemiluminescence system (Beijing 4A Biotech Co. Ltd., China) [24].…”