Curcumin-induced apoptosis in 3T3L1 cells
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signalling on the apoptotic action of curcumin, we examined the expression of PKA
catalytic subunits in Curcumin treated 3T3L1 adipocyte cells. We demonstrated
that Curcumin treatment blocked PKA catalytic subunit expression and inhibited
PKA relative activity (Figure 5A), especially at 24h post treatment (Figure 5B),,
which explained the gradual reduction in p-CREB levels (Figure 4). As Akt's
phosphorylation is required for its efficient activation (30), the p-Akt expression
was also examined and found that it has decreased but to a lesser extent than p-
CREB (Figure 4). This means that the apoptotic action of curcumin on 3T3L1 cells
is accompanied by decreasing p-CREB and p-Akt expression. This is consisting with
the function of CREB in mediating Akt’s action described by Wang et al.(46) and
Akt’s ability to phosphorylate CREB (47).
In contrast, these results disagree with the finding of Yeo et al (30) studying
prostaglandin-mediated anti-apoptotic action on monocytic HL-60 cells.
Adiponectin hormone concentrations are inversely correlated with body fat
% in adults (48). In transgenic mice, there was a reduction in adipocytes
differentiation following overexpression of adiponectin targeted to adipose tissue
(49) which is in agreement with other findings. Curcumin’s apoptotic effect was
accompanied by increased expression of both adiponectin and p-AMPK (Figure 4).
Adiponectin appears to be a growth antagonistic hormone in 3T3L1 adipocytes
and may promote apoptosis via the AMPK signal pathway. AMPK has a key role in
regulating cell metabolism, energy (50), cell growth, autophagy, and cell
reprogramming, (12). In the current study, AMPK was detected in 3T3L1 before
and 24-h post-curcumin treatment, a result that is supported by a previous study
of adipocytes and cancer cells, which found that curcumin plays a critical role on
cell differentiation and growth inhibition via AMPK activation (19, 12).
Upregulation of fatty acid oxidation is a physiological function of leptin and
adiponectin in skeletal muscle, and adipokines are able to carry out this function
through their effect on AMPK signalling (51, 52). Our findings demonstrated that
both adipokines and cAMP play a role in apoptosis and are supported by the study
on breast cancer cells by Naviglio et al, (9) who concluded that although leptin
inhibits adenylate cyclase/cAMP/PKA, elevating cAMP levels may be a novel
therapy for breast cancer. Furthermore, Hardie et al (53) demonstrated that
stimulators of AMPK may be of useful tools for preventing metabolic diseases.
In conclusion, curcumin modulates the phosphorylation of cellular
signalling molecules. Curcumin’s ability to inhibit the phosphorylation of
transcription factor in 3T3L1 could be attributed to the ability of AMPK to adapt to
acute changes in the metabolic enzymes via direct phosphorylation and through
decreased transcriptional response (54). In addition, AMPK reduced the
expression of CREB targets (12), and Curcumin decreased the expression of the
PKA catalytic subunit and inhibited levels of the phosphorylated protein factors p-
