Curcumin enhances the cytotoxic and chemo-sensitising effects of lenalidomide in human multiple myeloma cells

Abstract

Background: Curcumin, the active component of the Curcuma longa plant, has been shown to potentiate the effect of the immunomodulatory drugs (IMiDs) thalidomide and Bortezomib against human myeloma cell lines and a nude mice model. Its effect on the other IMid, lenalidomide, has not been evaluated. This study aims to investigate the mechanism of action of curcumin and its potential ability to positively interact with lenalidomide.Method: we designed an in-vitro study to investigate the cytotoxic and chemo-sensitising effects of curcumin alone and in combination with lenalidomide on the human myeloma H929 cell line. Results:Incubation of H929 cells with curcumin (30M) or lenalidomide (2.5 mM) for 3 days resulted in 26.35% (±1.06) and 30.81%(±2.98) apoptotic cells respectively. When 30 M curcumin was combined with 2.5 mM lenalidomide, 50.4% (±3.37) apoptotic cells were detected by flow cytometry and the increase was significant compared to either curcumin alone or lenalidomide alone (anova p = 0.0026). Furthermore, gene analysis studies show that curcumin enhances the cytotoxic effect of lenalidomide via suppression of the cereblon and multi-drug resistant genes. Conclusion:Curcumin exerts a cytotoxic effect additive to that of lenalidomide on H929 myeloma cells, and it also enhances the chemo-sensitizing effects of this agent.

Use of Curcumin in Multiple Myeloma patients intolerant of steroid therapy

“…Previous studies carried out in our clinics have demonstrated that oral administration of curcumin, even at high doses (up to 8 g daily), is well tolerated and can decrease the paraprotein load, free light chains, bone turnover, and % plasma cell dyscrasia in a selected group of patients with multiple myeloma precursor disease that is monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). [20][21][22][23] The multitude of published studies, including an in vitro study carried out in our laboratory, 16 suggest that curcumin can potentiate not only the cytotoxic effect of multiple agents used in the treatment of MM, but also enhance the chemo-sensitizing effects of these agents. The implications arising from these observations may be of important clinical benefit: i) curcumin studies can be designed to assess the additive antimyeloma effects of curcumin to the current treatment protocols and ii) curcumin may be used as an alternative to corticosteroids in such protocols.…”

“…The multitude of published studies, including an in vitro study carried out in our laboratory, suggest that curcumin can potentiate not only the cytotoxic effect of multiple agents used in the treatment of MM, but also enhance the chemo‐sensitizing effects of these agents. The implications arising from these observations may be of important clinical benefit: i) curcumin studies can be designed to assess the additive antimyeloma effects of curcumin to the current treatment protocols and ii) curcumin may be used as an alternative to corticosteroids in such protocols.…”

“…10,11 Curcumin has a demonstrated cytotoxic effect on myeloma activity 12,13 as well as a synergistic effect when used in combination with an IMiD or PI. 14,15 In a study by Wong et al, 16 curcumin was shown to enhance the cytotoxic and chemo-sensitizing effects of lenalidomide by suppressing the expression of the cereblon (CRBN) gene, which is a primary target for IMiD drugs like thalidomide and lenalidomide. 17 The same study also reported an enhanced reduction in the expression of the MRP gene, which encodes the multidrug resistant protein, when lenalidomide and curcumin are used together on H929 myeloma cell line.…”

Intense Uptake of Liposomal Curcumin by Multiple Myeloma Cell Lines: Comparison to Normal Lymphocytes, Red Blood Cells and Chronic Lymphocytic Leukemia Cells

“…Curcumin (diferuloylmethane) (Figure 1) is being investigated for its anticancer properties in a number of blood-borne cancer types, most notably, chronic lymphocyte leukemia (CLL) and myeloma, with several studies indicating its potential for therapeutic benefit (1)(2)(3)(4)(5)(6)(7)(8). The therapeutic benefits of curcumin in CLL have been extensively reviewed and a role in maintenance therapy proposed (1)(2)(3).…”

“…Curcumin has also been reported to play an immunomodulatory role in CLL in treatment of patients with CLL with Meriva ® , a nanocurcumin formulation of curcumin, resulted in an increase of CD4, CD8 and natural killer (NK) cells (6). In the multiple myeloma cell line NCI-H929, curcumin enhanced the cytotoxic and chemosensitizing effects of lenalidomide (7), while in U266 and RPMI-8226 cells, curcumin synergistically interacted with bortezomib to induce apoptosis (8). Curcumin has also been particularly of interest in the treatment of multiple myeloma because, unlike chemotherapy, it is toxic to cancer stem cells (9).…”