Curcumin & Psoriasis
Curcumin shows promise as powerful
skin disease (Psoriasis) treatment
In the Jan 2005 edition of Nature Medicine, researchers found a strong
linkage between psoriasis in mice and STAT3 activation. And according
to the PubMed database by the National Institute of Health, Curcumin (diferuloylmethane)
inhibits constitutive and IL-6-inducible STAT3 phosphorylation in human
multiple myeloma cells.
Curcumin (diferuloylmethane) inhibits constitutive and IL-6-inducible
STAT3 phosphorylation in human multiple myeloma cells.
Cytokine Research Section, Department of Bioimmunotherapy, Unit 143,
University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Numerous reports suggest that IL-6 promotes survival and proliferation of
multiple myeloma (MM) cells through the phosphorylation of a cell signaling
protein, STAT3. Thus, agents that suppress STAT3 phosphorylation have
potential for the treatment of MM. In the present report, we demonstrate
that curcumin (diferuloylmethane), a pharmacologically safe agent in humans,
inhibited IL-6-induced STAT3 phosphorylation and consequent STAT3 nuclear
translocation. Curcumin had no effect on STAT5 phosphorylation, but
inhibited the IFN-alpha-induced STAT1 phosphorylation. The constitutive
phosphorylation of STAT3 found in certain MM cells was also abrogated by
treatment with curcumin. Curcumin-induced inhibition of STAT3
phosphorylation was reversible. Compared with AG490, a well-characterized
Janus kinase 2 inhibitor, curcumin was a more rapid (30 min vs 8 h) and more
potent (10 micro M vs 100 micro M) inhibitor of STAT3 phosphorylation. In a
similar manner, the dose of curcumin completely suppressed proliferation of
MM cells; the same dose of AG490 had no effect. In contrast, a
cell-permeable STAT3 inhibitor peptide that can inhibit the STAT3
phosphorylation mediated by Src blocked the constitutive phosphorylation of
STAT3 and also suppressed the growth of myeloma cells. TNF-alpha and
lymphotoxin also induced the proliferation of MM cells, but through a
mechanism independent of STAT3 phosphorylation. In addition, dexamethasone-resistant
MM cells were found to be sensitive to curcumin. Overall, our results
demonstrated that curcumin was a potent inhibitor of STAT3 phosphorylation,
and this plays a role in the suppression of MM proliferation
M. D. Anderson researchers discover key protein in psoriasis
New find may be future target for medications to relieve common skin
HOUSTON - Researchers at The University of Texas M. D. Anderson Cancer
Center simultaneously have resolved a controversy over the cause of
psoriasis and developed the first mouse model that fully mimics the human
disorder. What's more, the scientists have demonstrated they can block the
signals that lead to psoriasis in their mouse model with a topical skin
treatment that can prevent new outbreaks as well as treat existing psoriatic
"We have developed a mouse model that exhibits all the major features of
human psoriatic lesions and shown we can reverse those steps," said John
DiGiovanni, Ph.D., the study's principal investigator and director of M. D.
Anderson's Department of Carcinogenesis. "We may have found an entirely new
treatment option for psoriasis."
The study, which appears in the January 2005 issue of the journal Nature
Medicine, available on-line Dec. 12, shows a protein called STAT3 is a
crucial initiator of psoriasis and must be present and activated for
psoriasis to develop in their mouse model.
Psoriasis is a chronic condition in which patches of skin become inflamed
and develop itchy red, flaky scales. Areas of the body most affected include
the scalp, elbows, knees, and lower back. Psoriasis affects about two
percent of people worldwide, with men and women equally susceptible. Current
treatment for psoriasis focuses on reducing inflammation and slowing down
the rapid growth and shedding of skin cells called keratinocytes. There is
no effective curative treatment for the underlying condition, according to
"There has been an ongoing controversy about whether the primary defect in
psoriasis is in the immune system or in the keratinocytes," says DiGiovanni.
"We may have found the link - the change in keratinocytes that cooperates
with the immune system cells necessary for development of human psoriasis."
The researchers became interested in STAT3 when they learned it was
associated with wound healing, a process that shares many of the same
molecular features with psoriasis and with cancer.
DiGiovanni's research team has recently shown that STAT3 is involved in the
development of skin cancer and began investigating its role in psoriasis,
another disease in which skin cells grow inappropriately.
STAT3 belong to a class of proteins called transcription factors, potent
proteins that can set off a cascade of events by simultaneously activating
many genes. In the case of STAT3, activation leads to the production of
growth-promoting and cell survival proteins. Activated STAT3 is essential in
normal skin to promote wound healing. When the healing process is complete,
normal STAT3 returns to its inactive form. But when it fails to turn off,
the wound healing process continues and skin cells proliferate.
The researchers first looked for activated STAT3 in the skin of psoriasis
patients and found high levels of activated STAT3 in psoriasis lesions in 19
of 21 patients. Based on this observation, the researchers decided to
develop a mouse model in which the gene that encodes STAT3 is always turned
on in the keratinocyte skin cells. When the genetically altered mice were
born they looked relatively normal, but by the time they were two weeks old,
they began to develop scaly patches on their tails that sometimes spread to
their lower back. When the scientists examined skin samples from the scaly
patches they discovered that the patches mimicked human psoriasis very
"This mouse model recapitulated all of the major epidermal and immunological
features of human psoriasis, something that other animal models fail to do,"
The researchers also noticed that if the animals suffered an abrasion, such
as when they scratch themselves, they frequently developed a scaly lesion in
the irritated area, just as many people develop psoriasis lesions after a
mild injury - a characteristic called the Koebner phenomenon. DiGiovanni
said this pattern is consistent with the idea that psoriasis is a form of
over-active wound healing response.
In another experiment, the scientists transplanted skin from their STAT3
mice to a mouse that produces no T cells, a key component of the immune
system that is believed to be necessary for development of psoriasis. The
transplanted skin did not initially develop psoriasis lesions. However, when
the scientists injected activated T cells into the skin grafts on T
cell-free mice, the mice then developed psoriasis following mild injury.
"This experiment showed it is necessary to have both activated STAT3 in
keratinocytes and infiltrating, activated T cells to develop psoriasis,"
said DiGiovanni. "Neither is sufficient alone."
The scientists then tested whether blocking STAT3 could reverse the
development of psoriasis. They applied a solution to the skin of their STAT3
mouse that contained a small piece of DNA called an oligonucleotide designed
to bind STAT3 and prevent it from activating genes. The STAT3-blocking agent
significantly halted the progress of the lesions and reversed symptoms such
as slowing cell growth, shrinking dilated blood capillaries and reducing
"This study opens the door to a whole new kind of therapy for psoriasis,"
said DiGiovanni. "This is a brand new target for treatment."
He also noted that certain aspects of psoriasis and early stages of cancer
development in skin share similarities. However, psoriasis never progresses
to cancer, he noted. "We still have much to learn about psoriasis, and this
mouse model will help us learn much more about the molecular events that
happen during the disease process," he said. In addition, it may help us
learn more about early stages of cancer and why certain changes favor one
disease versus the other."
DiGiovanni's collaborators included Shigetoshi Sano, M.D., Keith Syson Chan,
Ph.D., Steve Carbajal, Mary Peavey, and Kaoru Kiguchi, M.D., Ph.D., of M. D.
Anderson; John Clifford, Ph.D., Feist-Weiller Cancer Center and Louisiana
State University, Shreveport, La.; Brian Nickoloff, M.D., Ph.D., Loyola
University of Chicago; and Satoshi Itami, M.D., Ph.D., Osaka University
Graduate School of Medicine, Osaka, Japan.
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