CurCumin in multiple myeloma
Myeloma Today in conversation with Dr. Bharat Aggarwal
Please tell us about the use of natural products in
cancer therapy.
The use of natural products in cancer therapy is noth-
ing new. Between the years 1981 and 2002 almost
74% of all drugs approved by the US Food and Drug
Administration (FDA) were either natural products,
were based thereon, or mimicked them in one form or
another. Many of the active chemical entities in these
natural products have already been identified. So it is
a matter of course for our research group at the MD
Anderson Cancer Center to look for the treatment for
multiple myeloma in natural sources.
How are your studies related to myeloma?
We are studying the potential of natural products in
prevention and treatment of myeloma. The natural
product that my research group chose to focus on is
curcumin, which is the main biologically active phy-
tochemical derived from a plant called turmeric. In the
Western world, curcumin is sometimes referred to as
curry powder.
What does curcumin do in myeloma?
Curcumin has been described as an anti-inflammatory agent. Inflammation
is an ideal target to discover therapeutics for prevention and treatment
of cancer. Numerous genes that control tumorigenesis, the formation
of tumors in the body, also control inflammation. Curcumin is a very
potent blocker of a
pro-inflammatory
transcription fac-
tor called NF-κB
(nuclear factor-kap-
pa B). Several labo-
ratories, including
ours, have shown
that NF-κB plays a
very important role
in cancer. In myelo-
ma, it has been
shown that NF-κB
is active in promot-
ing myeloma cell proliferation. Curcumin suppresses the activation of
NF-κB. Our lab demonstrated in vitro that curcumin downregulates the
activation of NF-κB, which leads to inhibition of proliferation of myeloma
cell lines.
How did you proceed from that discovery?
We isolated myeloma cells that had been collected from patients and
exposed them to curcumin ex vivo, and this was very effective. Our next
step was a Phase I/II clinical trial in patients with myeloma, using 500 mg
capsules of curcumin. The objective of the trial was to evaluate the safety,
clinical tolerance, and biological effects of curcimin in myeloma patients
with asymptomatic, relapsed, or plateau-phase disease. Curcumin was
administered either alone orally at 2, 4, 6, 8, or 12 gms/day in two divided
doses, or in combination with Bioperine® (a standardized extract from
black pepper or long pepper) at 10 mg in two divided
doses for 12 weeks. Blood was collected before and
after treatment with curcumin and examined for
expression of NF-κB, cyclooxygenase (COX)-2 (an
enzyme that is regulated by NF-κB and controls
inflammation and proliferation), and phospho-STAT3
(signal transducer and activator of transcription) as
surrogate biomarkers.
What results did you obtain?
The results were quite interesting. We showed that
treatment with curcumin in combination with a
fixed dose of Bioperine was well tolerated. There
were no significant adverse events. Of the 29 evalu-
able myeloma patients treated so far, no objective
responses were noted.* However, 12 patients have
continued treatment for more than 12 weeks and five
of them have completed a full one year of treatment
with stable disease. Peripheral Blood Mononuclear
Cell (PBMC) examination of 28 of the evaluable 29
patients showed that oral administration of curcumin
significantly downregulated the constitutive activation
of NF-κB and STAT3, and suppressed COX2 expression. This study suc-
cessfully demonstrated, for the first time ever, that curcumin is a highly
safe agent that is bioavailable and can downregulate NF-κB, STAT3, and
COX2 in myeloma patients. This suggests a potential therapeutic role for
curcumin in myeloma that should be further investigated.
How do you view
the disconnect
between the
encouraging data
on curcumin
in the lab
with its lesser
effectiveness in
the patient?
Overall, cancer
treatment requires
suppression of
multiple cell-sig-
naling or survival pathways. Inhibition of single pathways is not adequate.
Curcumin is an ideal agent to investigate for the treatment and prevention
of myeloma, as it adapts multiple cell-signaling pathways, and is safe to
administer.
What about further investigations of curcumin for myeloma?
Our lab has already used curcumin in vivo and in vitro with Revlimid® and
with VELCADE®, and we have demonstrated that Revlimid and VELCADE
work better when combined with curcumin.
*No complete or partial responses were seen.
Editor’s Note: Dr. Aggarwal is Professor of Cancer Research and
Experimental Therapeutics, Division of Cancer Medicine, and Chief of
Cytokine Research Laboratory at the University of Texas MD Anderson
Cancer Center.
Bharat B. Aggarwal, PhD
University of Texas 
MD Anderson Cancer Center
Houston, TX