Despite advances in therapeutic approaches, the five-year survival rate for head and neck squamous cell carcinoma (HNSCC) patients is still less than fifty percent. Research has indicated that the consumption of Allium vegetables or processed garlic containing diallyl trisulfide (DATS) can lower the risk of multiple types of cancer. Nevertheless, the effectiveness and underlying mechanisms of DATS against HNSCC have not been thoroughly explored until the current study. In this research, it was found that DATS notably curtailed the growth and viability of HNSCC cells. Additionally, DATS triggered a significant G2/M cell cycle arrest in these cells, accumulating cyclin B1, Cip1/p21, and Ser-10 phospho-histone H3—this was indicative of mitotic arrest attenuated by NAC pretreatment, suggesting the role of reactive oxygen species (ROS) induction. The production of ROS induced by DATS led to DNA damage and apoptosis, a process associated with elevated levels of cleaved caspase-3 and cleaved PARP, along with reduced XIAP. When HNSCC cells were exposed to pharmacological concentrations of DATS, it resulted in the suppression of cancer stem cell (CSC) populations, as indicated by a decrease in the CD133high/CD44highcell fraction, reduced aldehyde dehydrogenase 1 (ALDH1) activity, inhibited spheroid formation and downregulatedSOX2andOct4expression. Furthermore, the administration of DATS to tumor xenografts demonstrated its in vivo capacity to hinder CSCs. Further, DATS treatment inhibited the growth of UMSCC-22B head and neck cancer tumor xenograft in immunocompromised mice. Overall, DATS inhibited cell proliferation; induced cell cycle mitotic arrest and apoptosis involving DNA damage through ROS generation; reduced the CSC fraction and spheroid formation; and downregulatedSOX2andOct4expression. More importantly, DATS inhibited HNSCC tumor growth and CSC fraction in vivo. Thus, DATS could be a potential anticancer agent that can be used against head and neck cancer.
尽管治疗方法有所进步，头颈部鳞状细胞癌患者的五年生存率仍低于50%。研究表明，食用含有二烯丙基三硫醚的葱属蔬菜或加工大蒜可降低多种癌症风险。然而，直至本研究开展前，二烯丙基三硫醚对头颈部鳞状细胞癌的作用效果及其潜在机制尚未得到充分探索。本研究发现，二烯丙基三硫醚能显著抑制头颈部鳞状细胞癌细胞的生长与活力。此外，该化合物可引发细胞周期G2/M期显著阻滞，导致细胞周期蛋白B1、Cip1/p21及丝氨酸10位点磷酸化组蛋白H3的积累——这一有丝分裂阻滞现象可被NAC预处理所减弱，提示活性氧诱导在此过程中发挥作用。二烯丙基三硫醚诱导产生的活性氧导致DNA损伤和细胞凋亡，该过程伴随裂解型caspase-3与裂解型PARP水平升高，以及XIAP表达降低。当头颈部鳞状细胞癌细胞暴露于药理学浓度的二烯丙基三硫醚时，癌症干细胞群体受到抑制，具体表现为CD133高表达/CD44高表达细胞比例下降、醛脱氢酶1活性降低、肿瘤球形成受抑以及SOX2和Oct4表达下调。此外，对肿瘤异种移植模型给予二烯丙基三硫醚的处理，证实了其在体内抑制癌症干细胞的能力。进一步实验显示，二烯丙基三硫醚治疗能抑制免疫缺陷小鼠体内UMSCC-22B头颈癌异种移植瘤的生长。总体而言，二烯丙基三硫醚通过以下机制发挥作用：抑制细胞增殖；通过活性氧生成诱导涉及DNA损伤的细胞有丝分裂阻滞与凋亡；减少癌症干细胞比例及肿瘤球形成；下调SOX2和Oct4表达。更重要的是，该化合物在体内能抑制头颈部鳞状细胞癌肿瘤生长并降低癌症干细胞比例。因此，二烯丙基三硫醚可能成为具有潜力的抗头颈癌药物。
肿瘤(癌症)患者之家