The improve in phospho-AMPK. A further nutraceutical, capsaicin, has been reported to activate AMPK and raise apoptosis in HT-29 colon cancer cells (182). Bcr-abl–The Bcr-abl oncoproteins are translocation-specific gene items in the Philadelphia chromosome which might be detectable in most CML. Bcr-abl regulates proliferation, survival, differentiation, and trafficking of hematopoietic cells by transcriptional and posttranscriptional mechanisms that demand tyrosine kinase activity and formation of multiprotein complexes whereby signaling molecules are assembled and activated within the cytoplasm and within the nucleus (183). The expression of Bcr-abl induces resistance of CML to apoptosis induced by chemotherapeutic drugs (184). Overexpression of Bcr-abl also protect against apoptotic cell death by inducing a Bcl-2 expression pathway in leukemia cells (185). Moreover, Bcr-abl has been shown to regulate c-jun gene expression, activation of c-Jun N-terminal kinase, as well as the ras pathway, which might also contribute to suppression of apoptosis, transformation, and tumorigenesis (186). Downstream mediators of Bcr-abl are known to regulate by the proteasome degradation. Various proteasome inhibitors which include bortezomib could suppress Bcr-abl signaling (187). Curcumin inhibits the proliferation of K562 cells and the impact is correlated with downregulation of p210bcr/abl (188). The underlying mechanism of curcumin in downregulating p210bcr/abl was identified later: It dissociates the binding of p210bcr/abl with Hsp90/p23 complex (189). A study carried out by William (190) showed that cur-cumin inhibits proliferation and induces apoptosis of leukemic cells expressing wild-type or T315I-BCRABL and prolongs survival of mice with acute lymphoblastic leukemia. Xhantho-humol was also reported to suppress Bcr-abl signaling. Mon-teghirofo et al. (191) showed that xanthohumol strongly inhibited Bcr-abl expression at both mRNA and protein levels. Hence, xanthohumol could induce apoptosis in all of Bcr-abl+ cells, CML cells, and clinical samples and retain its cytotoxicity in imatinib mesylate-resistant K562 cells (191). Raf/Ras–Raf is often a member of a serine/threonine certain protein kinase SR-PSOX/CXCL16 Proteins Storage & Stability family members and is an quick downstream target of Ras, that is implicated in the transduction of signals in the cell surface for the nucleus (192). In the resting cell, Ras is tightly bound to GDP. It is activated by binding of P-Selectin Proteins medchemexpress extracellular stimuli like development variables, RTKs, T-cell receptors, and phorbol-12 myristate-13 acetate (PMA) to cell membrane receptors. Activated Ras interacts especially with effector proteins, thereby initiating cascades of protein rotein interactions that may finally bring about regulation of cell proliferation, apoptosis, migration, fate specification, and differentiation (193). Ras also can activate numerous signaling pathways, which include Raf/MEK/ERK (extracellular signal-regulated kinases) pathway, the MEKK/SEK/JNK pathway, a PI3K/Akt/NF-B pathway, a p120-GAP/p190-B/Rac/NF-B pathway, and a Raf/MEKK1/inhibitor-B kinase (IKK)/NF-B pathway (194). Amongst the spicy nutraceuticals, curcumin showed sturdy inhibition on Ras and Ras-related pathways. Curcumin modulates the Ras signal transduction pathway and inhibits the proliferation of K562 cells (188). Limtrakul et al. (195) showed that orally consumedNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptNutr Cancer. Author manuscript; accessible in PMC 2013 Could 06.Sung et al.Pagecurcumin (0.