A major component of vitamin E, alpha-tocopherol inhibits the anti-tumor activity of crizotinib against cells transformed by EML4-ALK

作者：Uchihara Yuki; Kidokoro Takayuki; Tago Kenji; Mashino Tadahiko; Tamura Hiroomi; Funakoshi Tago Megumi^*

来源：European Journal of Pharmacology, 2018, 825: 1-9.

DOI：10.1016/j.ejphar.2018.02.012

• EML4-ALK
• Crizotinib
• NSCLC
• alpha-tocopherol
• Vitamin E

Crizotinib is an inhibitor of anaplastic lymphoma kinase (ALK) and is of significant therapeutic benefit to patients with non-small cell lung cancer (NSCLC) harboring the EML4-ALK fusion gene. In the present study, we demonstrated that alpha-tocopherol, a major component of vitamin E, attenuated the effects of crizotinib independently of its anti-oxidant properties. alpha-Tocopherol significantly inhibited crizotinib-induced apoptosis in cells transformed by EML4-ALK. It also effectively attenuated the crizotinib-induced inhibition of EML4-ALK and its downstream molecules, STAT3 and ERK, and suppressed the inhibitory effects of crizotinib on EML4-ALK-mediated transformation in the focus formation assay. On the other hand, other members of the vitamin E family, namely, beta-tocopherol, gamma-tocopherol, delta-tocopherol, and alpha-tocotrienol, and a water-soluble analog of vitamin E, Trolox had no effects on the anti-tumor activity of crizotinib in cells transformed by EML4-ALK. Collectively, these results revealed the risk of the anti-tumor activity of crizotinib being attenuated when it is administrated in combination with vitamin E supplements containing alpha-tocopherol as a major component.

• 出版日期2018-4-15