Different concentrations of shikonin induce either apoptosis or necroptosis, and necroptosis converts to apoptosis during the presence of Nec 1 in HL 60 and K562 cells. The growth inhibition and apoptosis induced by shikonin in some cancer cells can be attribu ted to the inactivation of NF B action or raising Annexin V signal and CD95 expression. Shikonin also induces apoptosis through ROS professional duction in osteosarcoma and Bcr/Abl favourable CML cells. A number of diverse mechanisms contribute on the anti cancer pursuits of shikonin. Such as, shikonin sup presses proteasomal pursuits thereby inhibiting tumor development in both H22 allografts and Computer three xenografts. Shikonin also inhibits topoisomerase II and down regulates ER2 and activates NFE2 relevant element 2 as an anti estrogen agent in human breast cancer.
Shikonin modulates an estrogen enzyme by down regulating the expression of steroid sulfatase that is crucial for estrogen biosynthesis. Shi konin inhibits tumor invasion by way of the NF B signaling pathway in human higher metastatic adenoid cystic carci noma cells. Therefore, shikonin may directly or selleck inhibitor indirectly inhibit or modulate disorder linked cellular targets in cancer. Emodin Emodin is usually a all-natural anthraquinone deriva tive isolated from Rheum palmatum L, with its dry raw herb consisting of up to 0. 20 mg/100 mg of emodin. Emodin exerts anti tumor activity towards various human cancers. Emodin induces cell cycle arrest and apoptosis in cancer cells as well as oxidative damage acts upstream of anti proliferation.
Emodin inhibits IL 6 induced Janus acti vated kinase 2/STAT3 pathways and induces selleck chemicals apoptosis in myeloma cells by way of the down regulation of Mcl one. Emodin down regulates androgen receptors and inhibits prostate cancer cell growth. Furthermore, emodin stabilizes topoisomerase II DNA cleavage com plexes, therefore inducing DNA double strand breaks. The suppression of excision fix cross comple mentation 1 and Rad51 expression by means of ERK1/2 inactivation is important in emodin induced cytotoxi city in human NSCLC cells. Emodin inhibits essential fibroblast growth component induced proliferation and migration in HUVEC and VEGF A induced tube formation. Emodin inhibits tumor cell migration as a result of suppression in the phos phatidylinositol 3 kinase Cdc42/Rac1 pathway. The disruption in the membrane lipid raft associated integrin signaling pathway by emodin may inhibit cell adhesion and spreading.
Emodin sensitizes chemotherapy connected with ROS production. In combined use with cisplatin, emodin elevates ROS generation and enhances chemo sensitivity in DU 145 cells, accompanied by the down regulation of MDR1 expression and suppression of HIF 1a transactivation. Emodin enhances the sensitiv ity of gallbladder cancer SGC996 cells to platinum medication through glutathione depletion and multidrug resistance related protein 1 down regulation.