Shikonin overcomes drug resistance and induces necroptosis by regulating the miR-92a-1-5p/MLKL axis in chronic myeloid leukemia.

ABSTRACT: Development of resistance to tyrosine kinase inhibitors (TKIs) targeting the BCR/ABL fusion protein represents a major challenge in the treatment of chronic myeloid leukemia (CML). Since apoptosis resistance is the fundamental mechanism impeding TKIs' therapeutic effects, alternative approaches that induce nonapoptotic cell death are being pursued to treat TKI-resistant CML. Induction of necroptosis, a distinct, caspase-independent form of programmed cell death, may be a valuable strategy in this respect. The present study shows that shikonin, an herbal compound used in traditional Chinese medicine, overcomes TKI resistance in BCR/ABL-positive CML cells by inducing necroptosis via activation of RIPK1/RIPK3/MLKL signaling. This effect occurs both in vitro and in vivo and involves downregula

SUBMITTER: Huang X 

PROVIDER: S-EPMC7521527 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature