Resveratrol Is a Natural Prevention and Treatment Option for Leukemia

Research suggests that resveratrol may be able to prevent certain types of leukemia, including those caused from radiation exposure (i.e., acute myeloid, chronic myeloid, and acute lymphocytic leukemias).^206-207 Resveratrol may also be a viable treatment option for the most common form of leukemia in adults (chronic lymphocytic leukemia, by itself or in combination with conventional chemotherapy drugs.²⁰⁸

This may be especially useful in older leukemia patients who cannot tolerate aggressive treatment regimens. Since resveratrol increases the effectiveness of these chemotherapy drugs lower dosages can be used, limiting the adverse side effects associated with conventional purine drugs for leukemia (e.g., suppressed immune system, infections, nausea, and vomiting).²⁰⁸

Understanding Leukemia

Leukemia is cancer of the blood and bone marrow where blood cells are generated from stem cells. In leukemia, the bone marrow makes abnormal white blood cells that have a negative impact on the functioning of other blood cells.²⁰⁹

The type of leukemia is dependent upon two factors:²¹⁰

• How quickly the number of leukemia cells increases.
• Type of stem cell the white blood cell develops from.

Acute leukemias develop and symptoms worsen rapidly. Chronic leukemias, on the other hand, sometimes develop so slowly that there may be no symptoms at all when the disease is discovered during a routine medical exam. Even when symptoms appear the course of the disease is gradual.

The risk factors for leukemia include:²⁰⁷

• Radiation exposure
• Smoking
• Exposure to benzene, a widely used chemical in many industries.
• Chemotherapy
• Heredity and genetic disorders (e.g., Down’s syndrome)

Evidence of Benefit

When tested on untreated cancer cells extracted from patients newly diagnosed with the most common form of leukemia in adults (chronic lymphocytic leukemia), resveratrol killed the cancer cells with no adverse effects on normal healthy cells. Resveratrol also increased the effectiveness of two conventional leukemia drugs (fludarabine and cladribine).²⁰⁸

However, recently published lab study data suggests that resveratrol could decrease the effectiveness of proteasome inhibitors, a type of chemotherapy drug (e.g., bortezomib). It appears to do so by causing the cancer cells to stop moving through the cell cycle before they begin to replicate, arresting them so they are considered nonproliferating, quiescent cells which are resistant to chemotherapy-induced cell death.²¹¹

Interestingly this same study on chronic myelogenous leukemia (K562) cells showed that resveratrol by itself could kill the cancer cells, at concentrations of 50-100 μM—although at lower levels than the chemotherapy drugs.²¹¹ In addition, other lab studies not only showed that resveratrol killed K562 leukemia cells at significant levels, but also helped overcome treatment resistance to a different type of chemotherapy drug. The researchers in this study indicated that this was likely due to resveratrol lowering levels of Hsp70, a heat shock protein associated with chemoresistance.²¹² The researchers in the proteasome inhibitor study suggested that the higher levels of cancer cell death found with resveratrol in this earlier study could be due to a measurements taken at 48 hours (rather than their 24 hours) and different methodology.²¹¹

New forms of resveratrol, such as the M8 analog, have been shown to be far more potent in lab studies on leukemia cell lines. Adding OH (hydroxy) groups to the base resveratrol form increases antioxidant power. In addition, M8 also targets and significantly inhibits the ribonucleotide reductase enzyme, which chemotherapy drugs (e.g., Ciclopirox olamine) for leukemia also target.^57,213

Animal Studies

Although resveratrol kills leukemia cancer cells (cell line 32Dp210) in lab experiments, one study published in 2002 showed that in mice were injected with chronic myeloid leukemia cells to induce the condition, resveratrol appeared to only exert weak anti-leukemia benefits. At the highest dosage of 80 mg/kg resveratrol showed limited effectiveness with only a 14% cure rate.²¹⁴

In one controlled animal study, oral doses of resveratrol significantly reduced DNA damage from radiation exposure (a known risk factor for leukemia). Both pre-treatment and treatment administered within hours of exposure showed the same benefit, both of which showed better protective results than doses administered two days after radiation exposure. The study author noted that resveratrol’s protective effect was a lot more effective when combined with muscadine grape extract.²⁰⁶

Another metabolite of resveratrol, piceatannol (PCA), significantly enhanced the therapeutic effects of the conventional chemotherapy agent cytosine arabinoside (Ara-C) under laboratory conditions by increasing the formation of its active form, Ara-CTP.²¹⁵ Ara-CTP is a nucleotide that the leukemia cancer cell incorporates into its own DNA which then inhibits DNA synthesis within the cell. This leads to cell death, with the number of cancer cells terminated is directly linked to the amount of Ara-CTP created.²¹⁶

Resveratrol has been shown in both lab and animal studies to help protect the heart from toxic side effects of the effective chemotherapy drug (arsenic trioxide) for cancers of the blood. Its antioxidant properties inhibit production of free radicals and irregular heart rhythms caused by the drug, decreasing injury to the heart muscle.²¹⁷