Curcumin and EGCG Suppress Apurinic/Apyrimidinic Endonuclease 1 and Induce Complete Remission in B-cell Non-Hodgkin's lymphoma Patients
Funct Food Health Dis. 2011; 1(12):525-44.
Non-Hodgkin’s Lymphoma (NHL) is a cancer that originates in the lymphatic system and can spread rapidly throughout the body. In NHL, tumors develop from lymphocytes—a type of white blood cells. There are many different types of NHL. These types can be divided into aggressive (fast-growing) and indolent (slow-growing) types and they can be formed from either B-cells or T-cells. Follicular lymphoma accounts for 20% of cases of lymphoma in the US, affecting the B cells and considered as a slow-growing lymphoma. Though often people with follicular lymphoma (FL) may show no apparent symptoms when diagnosed, 30–40% of patients with lymphoma may eventually develop into aggressive lymphoma and require chemotherapy. Although treatment of symptoms is an acceptable approach for FL but has limitations including relapses. Hence, oxidation-reduction (REDOX) signaling systems have been suggested as important targets in cancer. One of the proteins in this REDOX signaling system, AP Endonuclease 1 (APE1)/ redox factor-1 (Ref-1) is of great interest in B-cell follicular lymphoma. It is a key enzyme in base excision repair pathway, thus helping the DNA repair and survival of cells. However, in cancer cells such activity may lead to increased therapeutic resistance of cancer cells against DNA damage caused by regular chemotherapeutic/ionization treatments. This might negatively affect the outcome of such therapeutic pathways in cancer treatments. Elevated levels of APE1 are indicators of chemotherapeutic resistance, which are also known to induce COX-2 expression through the activation of NF-кB.
To examine the role of human APE1 in resistance and prognosis in FL patients and to evaluate safety and efficacy of combination of curcumin and epigallocatechin gallate (EGCG) therapy in non-Hodgkin follicular lymphoma patients and their peripheral blood mononuclear cells (PBMCs).
In this 9-month cohort trial a total of 40 subjects (10 healthy and 30 subjects with NHL) were treated with a combination of Curcumin C3 Complex® and EGCG containing green tea extract as an adjuvant to Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone (CHOP) therapy. The dosage of the green tea was kept at 9.0 g/day; provided in 1000 mg capsules, each containing 200 mg EGCG. Curcumin C3 Complex® capsules from America’s Finest Inc were given at doses between 0.9–5.4 g/day for 9 months. These 30 subjects with NHL were divided in 3 groups to receive either CHOP or CHOP-based chemotherapy with either Curcumin C3 Complex® or Curcumin C3 Complex®–EGCG combination.
The parameters evaluated during the trial (i.e. at baseline and at the end of the study) included fasting glucose level and lipid profile (total cholesterol, LDL-C, HDL-C and Triglycerides) along with liver and kidney function tests.
Blood samples were withdrawn from the patients at baseline and at specific intervals of 3, 6, 9 and 12 months of the treatment. The effect of Curcumin C3 Complex®-EGCG combination in reducing the drug resistance in NHL patients was estimated by determination of glutathione s-transferase activities, which plays a central role in the defense against free radicals.
- Results showed that Curcumin C3 Complex® alone or in combination with EGCG was able to inhibit the NF-кB activity and also sensitized lymphoma patients to CHOP therapy.
- There was a significant reduction in serum vascular endothelial growth factor (VEGF) in subjects receiving the combination of Curcumin C3 Complex® and EGCG.
- In Curcumin C3 Complex®-EGCG combination group GST level was found to be reduced.
- It has been known that GST is usually increased in most of human tumors and its high concentration increases the drug resistance. Hence, by lowering GST, combination of Curcumin C3 Complex®-EGCG was able to overcome chemotherapy resistance in NHL subjects
- It was also observed that patients on this combination remained disease-free for a mean of 8.6 years (range=7.9–9.2 years) after this combination therapy
Finally, authors concluded that combination of Curcumin C3 Complex®-EGCG can be helpful in decreasing the drug resistance and be a part of palliative regimen in NHL patients. Lost-lasting remission can be expected in such patients when CHOP therapy is supplemented with Curcumin C3 Complex®-EGCG combination.