The team of Motoyama in Kumamoto has recently published new results on folate-appended CDs in leukemia and ovarian cancer (1,2). FA-M-β-CD showed excellent cytotoxic activity in the reduced folate carrier (RFC) positive human ovarian cancer ES-2 cells line. It was found that the cytotoxic activity of FA-M-β-CD in ES-2 (RFC+) cells is unlikely to be a result of apoptosis triggered by a decrease in mitochondrial membrane potential. Moreover, FA-M-β-CD prolonged the survival of BALB/c nude mice bearing ES-2 (RFC+) cells. These results suggest the potential of FA-M-β-CD as an antitumor agent for treatment of metastatic ovarian cancer.
HP-β-CD has anti-leukemia activity by inducing apoptosis and cell-cycle arrest; however, the antitumor activity of HP-β-CD lacks tumor cell-selectivity. Taking advantage of the fact that folate receptors are highly expressed in many cancer cells, folate-appended HP-β-CD (FA-HP-β-CD) were synthesized to confer tumor cell-selectivity to HP-β-CD. FA-HP-β-CD inhibited the proliferation of chronic myeloid leukemia (CML) cells and the mechanism underlying the effect of FA-HP-β-CD in inducing cell death may involve autophagy. The combination of FA-HP-β-CD and ABL tyrosine kinase inhibitors (imatinib and ponatinib) had a synergistic inhibitory effect on CML cells. In a mouse model of BCR-ABL-induced leukemia, FA-HP-β-CD had a stronger inhibitory effect on leukemia progression than HP-β-CD or imatinib.
- Hoshiko, T.; Kubota, Y.; Onodera, R.; Higashi, T.; Yokoo, M.; Motoyama, K.; Kimura, S. Folic Acid-Appended Hydroxypropyl-β-Cyclodextrin Exhibits Potent Antitumor Activity in Chronic Myeloid Leukemia Cells via Autophagic Cell Death. Cancers 2021, 13, 5413. https://doi.org/10.3390/cancers13215413
- Onodera, R., Sakai, A., Tokuda, A. et al. The effect of folate-appended methyl-β-cyclodextrin increases on survival rates in a peritoneal dissemination mouse models of human ovarian cancer. J Incl Phenom Macrocycl Chem (2021). https://doi.org/10.1007/s10847-021-01109-y