Can anthocyanins improve maintenance therapy of Ph⁺ acute lymphoblastic leukaemia?

Abstract

Chemotherapy and tyrosine kinase inhibitors provide high remission rates. However, prognosis of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph(+) ALL) still remains poor. Because most adults eventually relapse without allogeneic stem cell transplantation, which is not available for all patients, novel strategies are required for relapse prevention. As the integrity of the immune system is essential for the control of remaining leukaemia cells, we compared the efficacy of anthocyanins, imatinib and a DNA-based vaccine as non-immunosuppressant components with 6-mercaptopurine (6-MP) to control minimal residual disease in vitro and in vivo using different leukaemia cell lines and syngeneic mice. Proliferation of Ph(+) ALL was significantly better inhibited by anthocyanin-rich berry extract or imatinib compared with 6-MP. Although anthocyanins induced apoptosis in some leukaemia cell lines, the level of caspase-3, caspase-8 and caspase-9 was significantly lower compared with imatinib and 6-MP. When used as single components, anthocyanins and imatinib mesylate failed to eradicate pre-existing Ph(+) ALL in syngeneic mice, while 6-MP led to 10% and DNA vaccination to 56% survival. Intriguingly, only the combination of DNA vaccination with berry extract but not with the isolated anthocyanin, cyanidin-3-rutinoside or imatinib further increased leukaemia-free and overall survival, and 90% of lethally challenged mice survived. We suggest that induction and enhancement of a leukaemia-specific immunity by DNA vaccination and anthocyanin-rich berry extract can also decrease the relapse rate in patients with Ph(+) ALL. Furthermore, this approach may serve as strategy for maintenance therapy of other malignancies.

An Anthocyanin-Rich Extract from Hibiscus sabdariffa Linnaeus Inhibits N-Nitrosomethylurea-Induced Leukemia in Rats

“…Our data demonstrate that an anthocyanin-rich diet (HAs) in fact is sufficient to enhance the antileukemia response, which is consistent with other studies. For instance, anthocyanin-rich berry extract significantly inhibits leukemia cell proliferation at 10−100 μg/mL, which corresponds to anthocyanin concentrations between 10 −6 and 10 −5 M. 45 There is some controversy about its bioavailabilty, but recent evidence indicates that despite low bioavailability, plasma concentrations of anthocyanins appear sufficient to induce changes in gene expression and signal transduction in vivo 46 in a manner suggesting a positive role in physiological functions and health outcomes. Several in vivo studies have provided evidence that plant foods have a notable impact on the absorption and metabolism of anthocyanins.…”

Anthocyanins as Immunomodulatory Dietary Supplements: A Nutraceutical Perspective and Micro-/Nano-Strategies for Enhanced Bioavailability

“…However, the most promising results were observed with DNA vaccination and the berry extract, leading to higher survival rates and reduced relapse rates. This suggests its potential to enhance leukemia-specific immunity and be a maintenance therapy for other malignancies [83]. Two polyphenol-rich juices were investigated in a randomized crossover study involving healthy men on a low-polyphenol diet.…”