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modulate leptin release from 3T3L1cells (4, 5). Different mechanisms for
physiological and pathological apoptosis processes have been investigated,
including suppressing signal transduction pathways to stimulate apoptosis (6).
Cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA)
functions as both a suppressor and activator of apoptosis. In arterial smooth
muscle cells adenosine-mediating apoptotic pathways are activated (7); however,
Zhang et al, (8) reported that the cAMP signalling pathway has been found to
either support or inhibit apoptosis, depending on cellular situation. The adipokine
leptin inhibits growth via apoptosis caused by adenylate cyclase/cAMP/PKA-
elevating agents in some cancer cells (9). Increase in weight is resulted due to the
growth and enlargement of adipose tissue, and AMPK is a major controller of
energy metabolism that increases fatty acid oxidation and suppresses lipid
accumulation (10,11). Mihaylova and Shaw (12) reported that in addition to
physiological AMP/ADP elevation stresses, AMPK can be stimulated by many
pharmacological agents and factors, including leptin, and AMPK in turn can
suppress cell growth by acting as a metabolic check point. AMPK also directly
phosphorylates some regulatory associated proteins and reduces expression of
cAMP response element-binding protein (CREB) targets, which is important since
CREB activation stimulates the expression of multiple transcription factors
required for adipogenesis (13). Reactive oxygen species (ROS) and mitochondria
play a prominent role in apoptosis as described by Simon et al. (14). Recently, it
was found that apoptosis is regulated by ROS through a variety mechanisms
depending on cell and conditioned media types (15). Adipose tissue growth is
sensitive to angiogenesis and adipogenesis inhibitors (16), as well as adipokines
(2) and these may serve as effective tools for controlling adipocytes growth.
Curcumin was reported as a potent inducer for apoptosis characteristics,
including cell fading, chromatin retraction, DNA fragmentation, and cell membrane
blebbing (6). The anti-angiogenic effect of curcumin in vivo was supported by its
action at the level of gene expression in modified media of cells treated with
different doses of curcumin (1 μM–1 mM) for various time durations (0–24 h) (17)
. Curcumin has been studied for its potential effect in antiangiogenic activity in
tumor (18) and in preventing obesity in C57BL mice and inhibiting adipogenesis in
3T3-L1 adipocytes (16) as well as cancers (19- 21). In contrast, Kim et al (22)
found that low concentration of curcumin activated proliferation, improved
stemness and migration of 3T3-L1 preadipocytes. Cellular survival required
Protein Kinase B (PKB or Akt1) through its inhibiting effect on apoptosis so it is
involved as principal factor in multiple cancers (23). But curcumin was able to
induce cell cycle arrest in different phases, including human osteosarcoma cells in
successive G(1)/S and G(2)/M phases (19) and on colorectal carcinoma cells in the
S phase (24). Recent studies described an inhibiting growth action of curcumin by
stimulation of adenosine 5'-monophosphate (AMP, also called activated protein
