Curcumin induces apoptosis via inhibition of PI3′-kinase/AKT pathway in Acute T cell Leukemias

Abstract

Curcumin has been shown to possess variety of biological functions including anti-tumor activity. The mechanism by which curcumin inhibit cell proliferation remains poorly understood. In the present report, we investigated the effect of curcumin on the activation of apoptotic pathway in T-cell acute lymphoblastic leukemia (T-ALL) malignant cells. Our data demonstrate that curcumin causes dose dependent suppression of proliferation in several T cell lines. Curcumin treatment causes the de-phosphorylation/inactivation of constitutively active AKT, FOXO transcription factor and GSK3. Curcumin also induces release of cytochrome c accompanied by activation of caspase-3 and PARP cleavage. In addition, zVAD-fmk, a universal inhibitor of caspases, prevents caspase-3 activation and abrogates cell death induced by curcumin treatment. Finally, treatment of T-ALL cells with curcumin down-regulated the expression of inhibitor of apoptosis protein (IAPs). Taken together, our finding suggest that curcumin suppresses constitutively activated targets of PI3'-kinase (AKT, FOXO and GSK3) in T cells leading to the inhibition of proliferation and induction of caspase-dependent apoptosis.

HGF/c-Met pathway has a prominent role in mediating antiapoptotic signals through AKT in epithelial ovarian carcinoma

“…28 Replicates of three wells for each dosage, including vehicle control, were analyzed for each experiment.…”

Coexpression of Activated c-Met and Death Receptor 5 Predicts Better Survival in Colorectal Carcinoma

“…Colo-320 and LOVO cells express appreciable levels of DR5, whereas HCT-15 and SW-480 cell lines express low levels of DR5. 28,34,35 For the detection of apoptosis, cells were harvested and the percentage apoptosis was measured by flow cytometry after staining with fluorescein-conjugated annexin V and propidium iodide (PI; Molecular Probes) and DNA laddering using a 1.5% agarose gel, as previously described. 36 …”

Role of pro-oxidants and antioxidants in the anti-inflammatory and apoptotic effects of curcumin (diferuloylmethane)

“…In fact, curcumin has been shown to bind to an active site in 5-LOX, and the two together have been cocrystallized [11]. This phytochemical has also been shown to suppress the proliferation of a wide variety of tumor cells by downregulating c-myc [6], cyclin D1 [12], activator protein-1 (AP-1) [13], phosphatidylinositol-3-kinase/AKT signaling [14], and epidermal growth factor receptor (EGFR) signaling [15]. Curcumin can also induce apoptosis through the modulation of antiapoptotic gene products [2,6] and BID cleavage, cytochrome c release, and caspase-9 activation, leading to caspase-3 activation [16].…”