Intravenous

Curcumin Therapy
Mark McCarty and Francisco Contreras, MD

While many cancers are initially responsive to chemotherapy, there is a well-known tendency
for cancers to develop resistance to chemotherapy over time. It is characteristic of most
cancers that their genetic material is highly prone to mutation and other types of heritable
changes known as “epigenetic shifts.” While most of these changes do not benefit cancer cells,
some types can confer resistance to chemotherapy. Clearly, cells that have developed such
changes in their DNA structure will be more likely to survive a cycle of chemotherapy, and then
proliferate to generate tumors that don’t respond to subsequent chemotherapy.

One the most common ways in which these changes can promote chemoresistance is to
induce continual activation of a protein complex known as “NF-kappaB.”1-6 This protein
complex is a “transcription factor,” which means that it interacts with DNA to either promote
or represses the synthesis of a number of proteins. The proteins produced in response to NF-
kappaB tend to protect cancers from chemo by blocking a process known as “apoptosis”,
which is the chief way that chemo kills cancer cells.7-11 Other proteins produced in response to
NF-kappaB, such as “mdr1,” act to expel chemo drugs from the cell.12, 13 NF-kappaB also
induces proteins that increase the rate of cancer cell proliferation, and that augment its
capacity to invade tissues and metastasize to distant sites.14-25 In short, elevated NF-kappaB
activation in cancers tends to render them resistant to chemo, while promoting their
proliferation and spread. For these reasons, scientists hold inhibition of cancer’s NF-kappaB
activity as a key goal in cancer therapy.

The increased activation of NF-kappaB in most cancers is usually caused by increased

activation of the enzyme IKKbeta. Fortunately, there are various phytochemicals and drugs
that can suppress the activity of IKKbeta. One of these is salicylic acid, a natural anti-
inflammatory agent long employed at Oasis of Hope Hospital.26-29 In its delivery form known as
“salsalate,” we administer it both as an adjuvant to chemotherapy and an aid for controlling
cancer spread. Unfortunately, salicylic acid dosing is limited as it can produce an annoying
auditory side effect. Therefore, salicylate alone often fails to achieve an optimal inhibition of
IKK-beta and NF-kappaB.

Another phytochemical which can inhibit IKKbeta, by direct binding, is the

compound curcumin, the compound that gives the spice turmeric its yellow color.30-32 In
rodent studies, high oral doses of curcumin exert cancer-chemosensitizing, cancer-retardant,
and anti-inflammatory effects that have been attributed to inhibition of NF-kappaB activity.
33-43 In rodent studies, high oral doses of curcumin exert cancer-chemosensitizing, cancer-

retardant, and anti-inflammatory effects that have been attributed to inhibition of NF-kappaB
activity. Naturally, cancer physicians have been eager to employ curcumin as an adjuvant in
human cancer therapy – but there is a significant obstacle to its effective use. The efficacy of
oral curcumin in humans, even in very high doses, has proven to be quite limited. In part, this is
because curcumin is an insoluble compound whose absorption is particularly inefficient in
humans. This difficulty can be surmounted, to a degree, by administering curcumin in
particulate forms that have better absorption. But the more fundamental problem with oral
curcumin is that, in humans, once curcumin is taken into the absorptive cells lining the
intestine, these cells immediately metabolize it to “reduced” forms that are incapable of
inhibiting NF-kappaB activity. Hence, owing both to poor absorbability and rapid metabolism,
oral curcumin has not realized the clinical potential that cancer scientists had hoped to see.

Oasis of Hope has been working diligently to overcome this limitation. Biochemists working
with Oasis of Hope have developed a “nanoparticulate” form of curcumin (very tiny particles)
that can safely be administered intravenously. This route of administration can render the poor
absorption of oral curcumin irrelevant because I.V. curcumin does not pass through the cells of
the intestinal lining to get to the cancer. The problem of rapid metabolism is also substantially
alleviated. Studies in rodent cancer models have shown that I.V. administration of curcumin is
quite effective for improving the chemosensitivity of many cancers. Oasis of Hope’s strategy is
to administer its I.V. curcumin just prior to oxidative therapies, so that NF-kappaB activity will
be repressed, decreasing the cancer’s expression of proteins that protect them from apoptosis.
In patients who tolerate salsalate adequately, the combination of oral salsalate and I.V.
curcumin can work synergistically to suppress NF-kappaB and lower cancer’s resistance against
treatment. Fortunately, I.V. curcumin is well tolerated, and does not cause the auditory side
effects that salicylic acid can.

Although NF-kappaB activation is not the only way in which cancers can evolve
chemoresistance, it is a common and prominent one. So Oasis of Hope’s cutting-edge
protocols for suppressing NF-kappaB activity have the potential both to boost and sustain the
responsiveness of many cancers to oxidative therapies including High Dose I.V. Vitamin C or, in
some cases, low dose chemotherapy.

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