Note that this is for PH+ ALL, but we have often debated the merits of Curcumin so I thought it was worth posting.
https://ash.confex.c...Paper48422.html
3559 Curcumin Potentiates Antitumor Activity of Imatinib Via Inhibition of the AKT /mTOR Signaling Pathway and Down-Regulation of Bcr-Abl Gene in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
Session: 614. Acute Lymphoblastic Leukemia - Therapy, excluding Transplantation: Poster III
Monday, December 10, 2012, 6:00 PM-8:00 PM
Hall B1-B2, Level 1, Building B (Georgia World Congress Center)
Yuping Gong, MD, PhD*, Yong Guo, MD, PhD* and Ting Niu, MD, PhD
Department of Hemotology, West China Hospital, Sichuan University, Chengdu, China
Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) is triggered by constitutively activated BCR-ABL and SRC family tyrosine kinases. They interact each other, then activate downstream growth-signaling pathways including Raf/MEK/ERK,Akt/mTOR and STAT5 pathways. The BCR-ABL tyrosine kinase inhibitor imatinib is the standard treatment for Ph+ leukemia. However, response rate of Ph+ ALL to imatinib is low, relapse is frequent and quick. Studies have documented the potential anti-tumor activities of curcumin, a yellow colored polyphenol from the perennial herb Curcuma longa. However, whether curcumin can be used in the therapy for Ph+ALL remains obscure. Here, we reported that curcumin induced autophagic cell death by activating RAF/MEK/ERK pathway in early stage of the 24-hour exposure course, later induced apoptosis by inhibiting AKT/mTOR, ABL/STAT5 signalings, down-regulating expression of bcr/abl gene and Bcl2 anti-apoptosis protein, and up-regulating the expression of pro-apoptosis protein BAX in Ph+ALL cell line SUP-B15. Furthermore, we found curcumin exerted synergetic anti-leukemia effect with imatinib by inhibiting imatinib-mediated up-regulation of the activation of AKT/mTOR signaling and down-regulating expression of bcr/abl gene. It is worth noting that curcumin provide advantages over dexmethasone as to synergetic anti-leukemia effect with imatinib because dexmethasone improved the imatinib-mediated up-regulation of the activation of AKT/mTOR/P70S6 signaling. In primary samples from Ph+ALL patients, curcumin inhibit growth signaling not only in newly-diagnosised patient but also in imatinib-resistant patient. Moreover, curcumin effectively exhibited anti-leukemia efficacy and synergetic anti-leukemia effect with imatinib in Ph+ALL mouse models. These results demonstrate that curcumin may be a promising agent for the treatment of patients with Ph+ ALL, and curcumin might be particularly effective when used with current induction regimens consisting of imatinib with or without chemotherapy for treating Ph+ ALL. [Grant Support:National Natural Science Foundation of China (No.30770912), Foundation of the Science & Technology Department of Sichuan Province (No.2008SZ0017)]
