Wang Yen-Yun, Xiao Ling-Yi, Chen Yuk-Kwan, Wu Pao-Chu, Chen Yi-Hua, Hu Stephen Chu-Sung, Yuan Shyng-Shiou F
School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
ACS Omega. 2020 Mar 23;5(12):7018-7024. doi: 10.1021/acsomega.0c00640. eCollection 2020 Mar 31.
Oral potentially malignant disorder (OPMD) is associated with an increased risk of progression to oral cancer. Patients with dysplastic changes of the precancerous lesions have a higher malignant transformation rate than those without dysplastic changes. Radiotherapy and surgery are the traditionally preferred choices for OPMD treatment. However, side effects caused by radiotherapy and surgery may reduce the willingness of patients to accept therapy. Therefore, developing an Orabase-formulated drug, which can be non-invasively administered, may provide an alternative treatment choice. To find, verify, and develop a new anti-cancer drug cost a lot of time and money, while drug repurposing can shorten both time and cost. In this study, we utilized high-throughput screening library to identify clinical drugs, which may have new bioactivities. Herein, we report that benzalkonium chloride (BAK), an antimicrobial preservative for pharmaceutical products, significantly induced reactive oxygen species production and cell death in oral precancerous cells. Additionally, our results showed that phosphorylation of STAT3 (Tyr705) and Akt (Ser473) were involved in cell death caused by BAK in DOK cells. According to animal studies, the development of DMBA-induced oral precancerous lesions was inhibited by 2% BAK. In conclusion, Orabase-formulated BAK may be a potential treatment for OPMD in the future.
口腔潜在恶性疾病（OPMD）与进展为口腔癌的风险增加相关。癌前病变有发育异常改变的患者比没有发育异常改变的患者有更高的恶变率。放疗和手术是OPMD治疗传统上首选的方法。然而，放疗和手术引起的副作用可能会降低患者接受治疗的意愿。因此，开发一种可以非侵入性给药的口腔膏剂配方药物可能会提供一种替代治疗选择。寻找、验证和开发一种新的抗癌药物需要花费大量的时间和金钱，而药物重新利用可以缩短时间和成本。在本研究中，我们利用高通量筛选文库来鉴定可能具有新生物活性的临床药物。在此，我们报告苯扎氯铵（BAK），一种药品的抗菌防腐剂，在口腔癌前细胞中显著诱导活性氧生成和细胞死亡。此外，我们的结果表明STAT3（Tyr705）和Akt（Ser473）的磷酸化参与了BAK在DOK细胞中引起的细胞死亡。根据动物研究，2%的BAK抑制了DMBA诱导的口腔癌前病变的发展。总之，口腔膏剂配方的BAK未来可能是OPMD的一种潜在治疗方法。
