A combined DNA-affinic molecule and N-mustard alkylating agent has an anti-cancer effect and induces autophagy in oral cancer cells

Wen Liang Lo*, Pen Yuan Chu, Tsung Heng Lee, Tsann Long Su, Yueh Chien, Yi Wei Chen, Pin I. Huang, Ling Ming Tseng, Pang Hsien Tu, Shou Yen Kao, Jeng Fan Lo

*此作品的通信作者

研究成果: Article同行評審

5 引文 斯高帕斯(Scopus)

摘要

Although surgery or the combination of chemotherapy and radiation are reported to improve the quality of life and reduce symptoms in patients with oral cancer, the prognosis of oral cancer remains generally poor. DNA alkylating agents, such as N-mustard, play an important role in cancer drug development. BO-1051 is a new 9-anilinoacridine N-mustard-derivative anti-cancer drug that can effectively target a variety of cancer cell lines and inhibit tumorigenesis in vivo. However, the underlying mechanism of BO-1051-mediated tumor suppression remains undetermined. In the present study, BO-1051 suppressed cell viability with a low IC50 in oral cancer cells, but not in normal gingival fibroblasts. Cell cycle analysis revealed that the tumor suppression by BO-1051 was accompanied by cell cycle arrest and downregulation of stemness genes. The enhanced conversion of LC3-I to LC3-II and the formation of acidic vesicular organelles indicated that BO-1501 induced autophagy. The expression of checkpoint kinases was upregulated as demonstrated with Western blot analysis, showing that BO-1051 could induce DNA damage and participate in DNA repair mechanisms. Furthermore, BO-1051 treatment alone exhibited a moderate tumor suppressive effect against xenograft tumor growth in immunocompromised mice. Importantly, the combination of BO-1051 and radiation led to a potent inhibition on xenograft tumorigenesis. Collectively, our findings demonstrated that BO-1051 exhibited a cytotoxic effect via cell cycle arrest and the induction of autophagy. Thus, the combination of BO-1051 and radiotherapy may be a feasible therapeutic strategy against oral cancer in the future.

原文English
頁(從 - 到)3277-3290
頁數14
期刊International Journal Of Molecular Sciences
13
發行號3
DOIs
出版狀態Published - 3月 2012

指紋

深入研究「A combined DNA-affinic molecule and N-mustard alkylating agent has an anti-cancer effect and induces autophagy in oral cancer cells」主題。共同形成了獨特的指紋。

引用此