Involvement of AMPK Signaling Cascade in Capsaicin‐Induced Apoptosis of HT‐29 Colon Cancer Cells

Abstract

Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is activated during ATP-depleting metabolic states, such as hypoxia, heat shock, oxidative stress, and exercise. As a highly conserved heterotrimeric kinase that functions as a major metabolic switch to maintain energy homeostasis, AMPK has been shown to exert as an intrinsic regulator of mammalian cell cycle. Moreover, AMPK cascade has emerged as an important pathway implicated in cancer control. In this article, we have investigated the effects of capsaicin on apoptosis in relation to AMPK activation in colon cancer cell. Capsaicin-induced apoptosis was revealed by the presence of nucleobodies in the capsaicin-treated HT-29 colon cancer cells. Concomitantly, the activation of AMPK and the increased expression of the inactive form of acetyl-CoA carboxylase (ACC) were detected in capsaicin-treated colon cancer cells. We showed that both capsaicin and 5'-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR), an AMPK activator possess the AMPK-activating capacity as well as apoptosis-inducing properties. Evidence of the association between AMPK activation and the increased apoptosis in HT-29 colon cancer cells by capsaicin treatment, and further findings of the correlation of the activated AMPK and the elevated apoptosis by cotreatment of AICAR and capsaicin support AMPK as an important component of apoptosis, as well as a possible target of cancer control.

A Comprehensive Review of the Carcinogenic and Anticarcinogenic Potential of Capsaicin

“…When incubated for 48 hr, !10 mM induced apoptosis through caspase-3 pathway activation and increased intracellular ceramide levels Kim et al 2007 Human colon cancer HT-29 Table 5. Human 5637 urothelial Induced more invasive and aggressive phenotype in TRPV1-null 5637 cells Up-regulated pro-angiogenetic and down-regulated apoptotic genes Pramanik et al 2011 Human BxPC-3 and AsPC-1 pancreatic 150 mM generated 4-to 6-fold more ROS but not in normal HPDE-6 cells; generation ROS was inhibited by catalase…”

Natural Polyphenols that Display Anticancer Properties through Inhibition of Kinase Activity

“…Due to their structural similarity with these acid derivatives, several others phenolic analogues are reviewed here even if they do not contain acid function ( Table 1). The polyphenols which exert anticancer activity by targeting specific kinases include capsaicinoid derivatives (8 and 9, vanilloid derivatives of branched-chain fatty acids), found in some peppers of the Capsicum plant family [19,20], [6]gingerol (10) and [6]-paradol (11), two phenols structurally related to the vanilloid moiety with 16 carbon atoms (C6-C10) [21,22], tyrosol derivatives (12 and 13, phenylethanol compounds with 8 carbon atoms (C6-C2)), present in a variety of natural sources [23,24], rosmarinic acid (14, phenolic derivative of caffeic acid with 18 carbon atoms (C6-C6-C6)), found in many Lamiaceae herbs [25], and curcumin (15, diferuloyl derivative containing 19 carbon atoms (C6-C7-C6)), isolated from the ginger family (Zingiberaceae) [26,27]. Curcumin has a highly conjugated structure, and it is a major pigment in mustard and turmeric.…”

“…The chemical name of the flavone backbone is 2-phenylchromen-4-one or 2-phenyl-1,4-benzopyrone ( Table 3). Flavones believed to exert anticancer properties through the inhibition of kinase activity include for example baicalein (18), baicalin (19), luteolin (20) and apigenin (21, Table 3) [46][47][48]. Natural flavonoids can be found either in free or conjugated forms ( Table 3).…”

“…Capsiate (8) interfered with angiogenesis and vascular permeability in HUVEC endothelial cells by direct inhibition of Src kinase, a tyrosine kinase (Table 1) [20]. Capsaicin (9), an analogue of capsiate (8), is known to activate, at a concentration of 25 M, adenosine monophosphate (AMP)-activated protein kinase (AMPK) and it induces apoptosis of HT-29 colon cancer cells [19]. [6]-Gingerol (10) was described as an inducer of apoptosis and cell growth arrest in human colorectal cancer cells (for example HCT-116) [22].…”

High dose of extracellular ATP switched autophagy to apoptosis in anchorage-dependent and anchorage-independent hepatoma cells

“…Activated AMPK is regarded as an efficient growth inhibitor and apoptosis inducer, even though the exact signaling transduced from AMPK has not been elucidated [18,19]. To determine whether the AMPK pathway was involved in the effect of eATP on anchorage-dependent hepatoma cells, we analyzed the activation of the AMPK pathway by using a specific antibody against the phosphorylated form of AMPK (Thr172).…”