Dou Jie, Wang Zhou, Ma Leon, Peng Bo, Mao Ke, Li Chengqin, Su Mengqi, Zhou Changlin, Peng Guangyong
State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, P. R. China.
Division of Infectious Diseases, Allergy and Immunology and Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA.
Oncotarget. 2018 Jan 8;9(28):20089-20102. doi: 10.18632/oncotarget.24015. eCollection 2018 Apr 13.
Baicalein and baicalin are active components of the Georgi and both have broad anti-tumor activity. However, how and whether baicalein and baicalin inhibit colon cancer is unclear. Here we demonstrate that baicalein and baicalin can significantly inhibit human colon cancer cell growth and proliferation. Furthermore, both can induce cell cycle arrest, and suppress cancer cell colony formation and migration. The suppressive effects are mechanistically due to the induction of colon cancer cell apoptosis and senescence mediated by baicalein and baicalin, respectively. Furthermore, we revealed that baicalin-induced senescence in tumor cells is due to its inhibition of telomerase reverse transcriptase expression in tumor cells, and that MAPK ERK and p38 signaling pathways are causatively involved in the regulation of colon cancer cell apoptosis and senescence mediated by baicalein and baicalin. In addition, our studies using human colon cancer cells in humanized mouse xenograft models, further demonstrated that baicalein and baicalin can induce tumor cell apoptosis and senescence, resulting in inhibition of tumorigenesis and growth of colon cancer . These data clearly suggest that baicalein and baicalin have potent anti-cancer effects against human colon cancer and could be potential novel and effective target drugs for cancer therapy.
黄芩素和黄芩苷是黄芩的活性成分,二者均具有广泛的抗肿瘤活性。然而,黄芩素和黄芩苷如何以及是否能抑制结肠癌尚不清楚。在此我们证明,黄芩素和黄芩苷可显著抑制人结肠癌细胞的生长和增殖。此外,二者均可诱导细胞周期停滞,并抑制癌细胞集落形成和迁移。这些抑制作用在机制上分别是由于黄芩素和黄芩苷介导的结肠癌细胞凋亡和衰老。此外,我们发现黄芩苷诱导肿瘤细胞衰老的原因是其抑制肿瘤细胞中的端粒酶逆转录酶表达,并且丝裂原活化蛋白激酶(MAPK)细胞外信号调节激酶(ERK)和p38信号通路分别参与了黄芩素和黄芩苷介导的结肠癌细胞凋亡和衰老的调控。此外,我们使用人源化小鼠异种移植模型中的人结肠癌细胞进行的研究进一步证明,黄芩素和黄芩苷可诱导肿瘤细胞凋亡和衰老,从而抑制结肠癌的发生和生长。这些数据清楚地表明,黄芩素和黄芩苷对人结肠癌具有强大的抗癌作用,可能是癌症治疗中潜在的新型有效靶向药物。