On top of that, cryptotan shinone suppressed the binding of STAT3 to DNA in a dose dependent manner. Even so, cryptotan shinone also inhibited the phosphorylation of JAK2, an upstream kinase of STAT3 or five while in the cells. Apart from, cryptotanshinone led to greater expression of SHP 1, but no effect over the expression of SHP 2. three. four. Tanshinone IIA and Cryptotanshinone Induce Apoptosis in K562 Cells. JAK/STAT signaling regulates gene items concerned in many cellular processes such as survival, pro liferation, and cell cycle progression. The two tan shinone IIA and cryptotanshinone substantially attenuated the expression of STAT related survival genes for instance bcl xL, surviving, and cyclin D1 in a dose dependent manner. On the other hand, only tanshinone IIA, but not crypto tanshinone, suppressed the expression of antiapoptotic mcl 1L in K562 cells, left panel.
To confirm that tanshinone IIA or cryptotanshinone can induce apoptosis, activation of caspase 9 and three, crucial molecules in intrinsic apoptosis pathway, was evaluated by immunoblotting. As expected, the two tanshinone IIA and cryptotanshinone obviously induced the cleavages of caspase 9 and three too as PARP in the dose dependent method. Consis read review tently, cell cycle analysis showed enhanced accumulation from the sub G1 cell from 0. 22% to 17. 19% or 17. 60% by tanshinone IIA or cryptotanshinone in K562 cells, respectively. Also, we noticed that treatment of 20 M tanshi none IIA or cryptotanshinone considerably increased the apoptotic cell population by Annexin V PI double staining to 23. 96 and 18. 01%, respectively. three. 5. Tanshinone IIA and Cryptotanshinone BI6727 Synergistically Advertise Anticancer Effects with Imatinib in K562 Cells. Bcr abl is an abnormal gene formed by the reciprocal translo cation involving chromosomes 9 and 22 in CML.
We examined whether tanshinone IIA or cryptotanshinone can affect activation of bcr abl by Western blotting. As shown in Figure five, the two tanshinone IIA and cryptotanshinone diminished phosphorylation of bcr abl in the dose dependent method. Then, to test the synergy amongst tanshinone IIA or cryptotanshinone and imatinib, a aggressive tyrosine kinase inhibitor used in the remedy of CML, K562 cells had been cotreated with tanshinone IIA or cryptotanshinone during the absence or presence of imatinib for 24 h. The cell viability was appreciably decreased in combina tion of tanshinone IIA or cryptotanshinone with imatinib in the dose dependent method compared to untreated handle. Tanshinone IIA remarkably showed the syner gistic impact on the imatinib induced apoptosis with CI worth 0. 315 and 0. 628 at two. 5 and five M, respectively. In contrast, cryptotanshinone treatment method with imatinib had the synergistic effect only at 2.