Home
Resources
Publications
Spautin-1, a Novel Autophagy Inhibitor, Enhances Imatinib-Induced Apoptosis in Chronic Myeloid Leukemia

Spautin-1, a Novel Autophagy Inhibitor, Enhances Imatinib-Induced Apoptosis in Chronic Myeloid Leukemia

Shan Shao, Su Li, Youwen Qin, Xiaorui Wang, Yining Yang, Haitao Bai, Lili Zhou, Chuxian Zhao, Chun Wang

Int J Oncol. 2014 May;44(5):1661-8.

PMID: 24585095

Abstract:

Imatinib mesylate (IM), a targeted competitive inhibitor of the BCR-ABL tyrosine kinase, has revolutionized the clinical treatment of chronic myeloid leukemia (CML). However, resistance and intolerance are still a challenge in the treatment of CML. Autophagy has been proposed to play a role in IM resistance. To investigate the anti-leukemic activity of specific and potent autophagy inhibitor-1 (spautin-1) in CML, we detected its synergistic effect with IM in K562 and CML cells. Our results showed that spautin-1 markedly inhibited IM-induced autophagy in CML cells by downregulating Beclin-1. Spautin-1 enhanced IM-induced CML cell apoptosis by reducing the expression of the anti-apoptotic proteins Mcl-1 and Bcl-2. We further demonstrated that the pro-apoptotic activity of spautin-1 was associated with activation of GSK3β, an important downstream effector of PI3K/AKT. The findings indicate that the autophagy inhibitor spautin-1 enhances IM-induced apoptosis by inactivating PI3K/AKT and activating downstream GSK3β, leading to downregulation of Mcl-1 and Bcl-2, which represents a promising approach to improve the efficacy of IM in the treatment of patients with CML.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1262888287	Spautin-1		1262888-28-7	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: