AbMole丨Shikonin：从诱导细胞死亡程序到调节信号通路

Shikonin紫草素AbMoleM4240是一种从紫草根中分离的萘醌类化合物在多种研究中显示出广泛的生物活性。在细胞实验中Shikonin对HTR-8/SVneo细胞的活力表现出浓度和时间依赖性抑制其作用机制涉及诱导细胞的焦亡[1]。ShikoninCAS No.517-89-5在胃癌NCI-N87细胞中显著抑制细胞增殖并影响凋亡相关蛋白Bax和Bcl-2的表达[2]。此外Shikonin紫草素在SCLC细胞中通过抑制ERK信号通路和诱导铁死亡显著抑制细胞增殖、迁移和侵袭[3]。在乳腺癌4T1细胞中Shikonin通过诱导线粒体功能障碍和ROS产生抑制细胞增殖并在小鼠原位模型中表现出肿瘤生长抑制和免疫调节作用[4]。Shikonin在肾癌Caki-1和ACHN细胞中通过浓度依赖性方式触发细胞坏死和凋亡其作用可被N-乙酰半胱氨酸AcetylcysteineNAC一种ROS清除剂部分逆转。Shikonin紫草素在胰腺癌细胞中通过抑制PAK1激酶活性IC50为7.252 ± 0.054 μM发挥抗肿瘤作用[5]。在动物实验中Shikonin50.0 mg/kg通过调节miRNA-140-5p/TLR4信号通路在小鼠急性肺损伤模型中表现出显著的保护作用[6]。此外Shikonin在胚绒毛尿囊膜CAM模型中通过抑制细胞增殖和诱导凋亡显著减少甲状腺髓样癌细胞的生长[7]。在神经炎症研究中Shikonin通过抑制海马区炎症反应表现出抗抑郁和抗焦虑样作用[8]。这些研究揭示了Shikonin紫草素AbMoleM4240在多种细胞模型如HTR-8/SVneo、NCI-N87、HT29、4T1、Caki-1、ACHN等和动物模型如小鼠、鸡胚中的广泛作用其机制涉及焦亡、凋亡、铁死亡、ROS调节、信号通路抑制等多种途径。参考文献及鸣谢[1] Zeng, F.; Lai, Y.; Huang, Y.; et al. Shikonin from lithospermum erythrorhizon induces pyroptosis in trophoblast cells by activating the CTSB-NLRP3 inflammasome. Annals of medicine2024, 56 (1), 2394584.[2] Jia, L.; Zhu, Z.; Li, H.; et al. Shikonin inhibits proliferation, migration, invasion and promotes apoptosis in NCI-N87 cells via inhibition of PI3K/AKT signal pathway. Artificial cells, nanomedicine, and biotechnology2019, 47 (1), 2662-2669.[3] Qian, X.; Zhu, L.; Xu, M.; et al. Shikonin suppresses small cell lung cancer growth via inducing ATF3-mediated ferroptosis to promote ROS accumulation. Chemico-biological interactions2023, 382, 110588.[4] Yu, C.; Xing, H.; Fu, X.; et al. Effect and mechanisms of shikonin on breast cancer cells in vitro and in vivo. BMC complementary medicine and therapies2024, 24 (1), 389.[5] Ji, W.; Sun, X.; Gao, Y.; et al. Natural Compound Shikonin Is a Novel PAK1 Inhibitor and Enhances Efficacy of Chemotherapy against Pancreatic Cancer Cells. Molecules (Basel, Switzerland)2022, 27 (9).[6] Zhang, Y. Y.; Liu, X.; Zhang, X.; et al. Shikonin improve sepsis-induced lung injury via regulation of miRNA-140-5p/TLR4-a vitro and vivo study. Journal of cellular biochemistry2020, 121 (3), 2103-2117.[7] Hasenoehrl, C.; Schwach, G.; Ghaffari-Tabrizi-Wizsy, N.; et al. Anti-tumor effects of shikonin derivatives on human medullary thyroid carcinoma cells. Endocrine connections2017, 6 (2), 53-62.[8] Shi, C.; Qi, Z.; Yang, C.; et al. Shikonin ameliorates depressive- and anxiogenic-like behaviors in rats via the suppression of inflammation in the hippocampus. Neuroscience letters2024, 837, 137893.