Antitumor effect of the integrin α4 signaling inhibitor JK273 in non-small cell lung cancer NCI-H460 cells

• DOI: 10.1016/j.bbrc.2017.07.096
• Publication Date: 2017-07-17T13:30:09Z
• Authors: Thien Nhan Lu; Bogonda Ganganna; Thuy Trang Pham; Anh Van Vo; Thien Phuc Lu; Huong-Giang Thi N...; My-Nuong Thi Nguyen; Phuong Nguyen Huynh; Ngoc Tuyen Truong; Jongkook Lee
• Keywords: Aniline Compounds; Cell Survival; Integrin alpha4; Gene Expression; Antineoplastic Agents; Apoptosis; Hep G2 Cells; Phosphatidylserines; Respiratory Mucosa; S Phase; 3. Good health; Inhibitory Concentration 50; Jurkat Cells; 03 medical and health sciences; 0302 clinical medicine; Cell Movement; Organ Specificity; Cell Line, Tumor; MCF-7 Cells; Humans; Cell Proliferation; HeLa Cells; Signal Transduction

Lung cancer accounts for the highest death rate among cancers worldwide, with most patients being diagnosed with non-small cell lung cancer (NSCLC), urging more effective therapies. We report that JK273, a pyrrolo[2,3-d]pyrimidine analog, which inhibits α4 integrin signaling, showed a selective cytotoxic effect against HCI-H460 NSCLC cells, with an IC50 of 0.98 ± 0.15 μM, but showed less sensitivity to fibroblasts with a selectivity index (SI) greater than 30. This effect was attributed to cell cycle arrest at S phase by JK273 treatment, resulting in the apoptosis of NCI-H460 cells, further confirmed by exposing phosphatidylserine and morphological changes. Taken together with the previous study of JK273 inhibiting cell migration, we propose that JK273 could serve as an antitumor compound to specifically target cancer cells but not non-cancerous cells by triggering programmed cell death, in addition to anti-metastatic effects in cancer therapy.