Folate-Appended Hydroxypropyl-β-Cyclodextrin Induces Autophagic Cell Death in Acute Myeloid Leukemia Cells

drug development, , ,

More and more uses of cyclodextrin as anticancer therapy agents come to light these days. The most recent is the research of Kumamoto University (who else) showing how Folate-Appended Hydroxypropyl-β-Cyclodextrin (FA-HP-β-CyD) Induces Autophagic Cell Death in Acute Myeloid Leukemia (AML) Cells.

As reported the cytotoxic activity of FA-HP-β-CyD against AML cells was stronger than that of HP-β-CyD. Also, FA-HP-CyD induced the formation of autophagosomes in AML cell lines. FA-HP-β-CyD increased the inhibitory effects of cytarabine and a BCL-2-selective inhibitor, Venetoclax, which are commonly used treat elderly AML patients. Notably, FA-HP-β-CyD suppressed the proliferation of AML cells in BALB/c nude recombinase-activating gene-2 (Rag-2)/Janus kinase 3 (Jak3) double-deficient mice with AML. These results suggest that FA-HP-β-CyD acts as a potent anticancer agent for AML chemotherapy by regulating.

IJMS | Free Full-Text | Folate-Appended Hydroxypropyl-β-Cyclodextrin Induces Autophagic Cell Death in Acute Myeloid Leukemia Cells (mdpi.com)

Figure 2
FA-HP-β-CyD induces apoptosis in HL-60, THP1, SKM1, and Kasumi1 cells. (A) HL-60, THP1, SKM1, and Kasumi1 cells were treated with 0 (medium only), 0.5, 1.0, and 1.5 mM of FA-HP-β-CyD for 72 h. After 72 h, cells were stained with Annexin V and PI. Representative FCM plots are shown (n = 3). (B–E) Percentage of Annexin V-positive PI-negative cells after exposure to FA-HP-β-CyD for 72 h. (B) HL-60, (C) THP1, (D) Kasumi1, (E) SKM1 cells. Data represent the mean ± SEM of three independent experiments. * p < 0.05.

Differences in the Intracellular Localization of Methylated β-Cyclodextrins-Threaded Polyrotaxanes Lead to Different Cellular States

Today's cyclodextrin, ,

Today’s cyclodextrin is an essential paper on understanding differences in internalization and cellular location of various polyrotaxanes by Hokkaido University, Japan Science and Technology Agency (JST) and Tokyo Medical and Dental University

Activation of autophagy represents a potential therapeutic strategy for the treatment of diseases that are caused by the accumulation of defective proteins and the formation of abnormal organelles. Methylated β-cyclodextrins-threaded polyrotaxane (Me-PRX), a supramolecular structured polymer, induces autophagy by interacting with the endoplasmic reticulum. The same level of autophagy induction was achieved at one-twentieth the dosage for the mitochondria-targeted nanocarrier (Me-PRX) compared to the naked Me-PRX. The quantitative evaluation of the intracellular organelle localization of both naked Me-PRX and the MITO-Porter (Me-PRX) are reported here. Mitochondria, endoplasmic reticulum and lysosomes were selected as target organelles because they would be involved in autophagy induction. In addition, organelle injury and cell viability assays were performed. The results showed that the naked Me-PRX and the MITO-Porter (Me-PRX) were localized in different intracellular organelles, and organelle injury was different, depending on the route of administration, indicating that different organelles contribute to autophagy induction. These findings indicate that the organelle to which the autophagy-inducing molecules are delivered plays an important role in the level of induction of autophagy.

Biomolecules | Free Full-Text | Differences in the Intracellular Localization of Methylated &beta;-Cyclodextrins-Threaded Polyrotaxanes Lead to Different Cellular States (mdpi.com)