Physician Scientist - American Association of Physicians of Indian ...

FEATURE
AAPI Journal • June 2009
Turmeric and Breast Cancer
by Hari Sharma, M.D.
Hari Sharma, M.D.
Columbus, Ohio
Breast cancer continues to be a
leading cause of cancer-related
death among women worldwide. An
estimated 182,460 new cases of
invasive breast cancer occurred in
the United States alone in 2008.
Turmeric (Curcuma longa), a spice
that is widely used in South Asian
cooking, has long been utilized in
Ayurveda for the treatment of a wide
variety of disorders and diseases
involving the skin, liver, pulmonary
and gastrointestinal systems, as well
as wounds, sprains, aches and pains.
Curcumin, the pigment that gives
turmeric its orange-yellow color, has
been referred to as an ‘age-old
NSAID’ (nonsteroidal antiinflammatory
drug). The antiinflammatory
properties of turmeric
and curcumin have been extensively
researched over the last 20 years in
relation to a multitude of disease
processes including neurodegenerative,
cardiovascular,
pulmonary, metabolic, autoimmune,
and neoplastic. Curcumin modulates
multiple cell-signaling pathways
known to be involved in the
pathogenesis of various chronic
diseases. It downregulates
inflammatory transcription factors
such as nuclear factor kappa B (NF-
_B), enzymes such as
cyclooxygenase-2 (COX-2), and
inflammatory cytokines.
Curcumin’s inhibition of multiple
proinflammatory pathways has been
heavily researched in relation to
cancer. More than 800 studies have
been published to date
demonstrating the anticancer
potential of curcumin. With regard
to breast cancer, curcumin exerts
multiple suppressive effects on
human breast tumor cell lines,
including hormone-dependent,
hormone-independent, and multidrug
resistant lines. Effects of
curcumin include the inhibition of
growth, as well as inhibition of
invasion and angiogenesis.
Curcumin induces apoptosis in
breast cancer cells by regulating
multiple signaling pathways. In an
animal study, curcumin inhibited
7,12-dimethylbenz[a]anthracene
(DMBA)-induced mammary
tumorigenesis. This inhibition was
associated with a significant
decrease in formation of DMBA-
DNA adducts in the animals
administered curcumin.
Curcumin suppresses activation of
the transcription factor NF-_B,
which is involved in inflammation,
tumor promotion and progression,
angiogenesis, invasion, and
metastasis. NF-_B is constitutively
activated in breast cancer cells and
correlates with the metastatic
potential of breast tumors. It has
been proposed as both a prognostic
marker and a molecular target in
breast cancer therapy. In an animal
model, curcumin reduced NF-_B
activity resulting in the prevention of
hematogenous breast cancer
metastases. There was a significantly
lower number of lung metastases in
the animals treated with curcumin;
68% of curcumin-treated animals vs.
17% of untreated animals had no or
very few lung metastases. A study
utilizing curcumin and paclitaxel
(Taxol) showed that curcumin
improves the therapeutic outcome of
paclitaxel treatment. Paclitaxel has
been used as a front-line
chemotherapeutic agent for breast
cancer; however, it can induce drug
resistance, possibly through the
activation of NF-_B, and therefore is
not useful in treating advanced
breast cancer. In breast cancer cells,
curcumin blocked paclitaxelinduced
NF-_B activation. In an
animal model used in this study,
curcumin inhibited human breast
cancer metastasis to the lung.
Treatment with paclitaxel modestly
reduced the incidence of metastasis,
however curcumin alone and
curcumin plus paclitaxel
significantly reduced the incidence
and number of lung metastases.
To further elucidate the
mechanism of action for curcumin’s
strong antimetastatic effect, an
analysis was carried out on the
complete range of curcumin’s effects
on gene transcription in a metastatic
breast cancer cell line. It was
discovered that curcumin alters the
expression of multiple genes,
including downregulating two
inflammatory cytokines known as
CXCL1 and CXCL2. The genes for
these cytokines are regulated by
NF-_B. CXCL1 and 2 are both
associated with tumor progression,
and CXCL1 is overexpressed by
breast cancer cells with an
increased potential to metastasize to
the lung. The downregulation of
these cytokines in turn leads to
downregulation of several
metastasis-promoting genes,
including the cytokine receptor
CXCR4, which has been implicated
in the promotion of metastasis in
breast cancer.
Continued on page 18
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