The anthelmintic agent oxfendazole inhibits cell growth in non‑small cell lung cancer by suppressing c‑Src activation

Abstract

The c-Src protein family of tyrosine kinases are important in the tumorigenesis of many types of tumors, and may be a potential target for antitumor drug discovery. In the present study, immunoblotting was performed to analyze protein expression, CCK-8 assay was carried out to assess cell viability and cell cycle was analyzed using a flow cytometer. The anthelmintic agent oxfendazole was observed to be a novel c-Src inhibitor that blocked the activation of c-Src. Oxfendazole also suppressed the cell growth of non-small cell lung cancer (NSCLC) cells, and overexpression of c-Src decreased the cytotoxicity of oxfendazole against NSCLC cells. In addition, oxfendazole induced cell cycle arrest at the G 0 /G 1 phase, and downregulated the protein levels of Cyclin-dependent kinase (CDK)-4, CDK6, retinoblastoma protein and E2 transcription factor 1, and upregulated the expression levels of p53 and p21 in NSCLC cells. Furthermore, oxfendazole enhanced the cytotoxicity of cisplatin against NSCLC cells. These results demonstrated that oxfendazole exerted its antitumor activity by suppressing c-Src signaling, and it was also indicated that the anthelmintic agent oxfendazole may be effective for anti-NSCLC therapy in the clinic as a single agent or in combination with other antitumor drugs.

The Antitumor Potentials of Benzimidazole Anthelmintics as Repurposing Drugs

“…Supplementary Table 1 ( 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 ) summarizes the antitumorigenicity of benzimidazole anthelmintics on cancer cell lines. Benzimidazole anthelmintics inhibit the progression of cancer through a variety of mechanisms.…”

“…The p53 wild-type cancer cells have a higher sensitivity to benzimidazole anthelmintics compared with the p53 mutant cells ( 38 ). Benzimidazole anthelmintics increased pp53, p53, and p21 but decreased mutant p53, mouse double minute 2 homolog (Mdm2; sometimes increased), mouse double minute 4 (MdmX), CDK4, CDK6, and pRB ( 22 23 58 59 ).…”

Anti-cancer effects of fenbendazole on 5-fluorouracil-resistant colorectal cancer cells

“…Benzimidazole is known to activate p53 and p21 but decrease mutant p53 expression [ 30 , 46 ]. Cancer cells with wild-type p53 showed higher sensitivity to fenbendazole compared with p53 mutant cells [ 5 , 35 ].…”

Ubiquitin‐specific protease 44 inhibits cell growth by suppressing AKT signaling in non‐small cell lung cancer

“…Lung cancer is consist of non‐small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) . Among these, NSCLC accounts for about 80% of all lung cancers, and about 75% of the patients were found to have low 5‐year survival . NSCLC mainly includes lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and large cell carcinoma .…”

“…4 Among these, NSCLC accounts for about 80% of all lung cancers, and about 75% of the patients were found to have low 5-year survival. 5,6 NSCLC mainly includes lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and large cell carcinoma. 7 Therefore, studying the pathogenesis of NSCLC will be very important for developing new therapeutic strategies in the future.…”