Curcumin in treatment of hematological cancers: Promises and challenges

Abstract

Hematological cancers include leukemia, myeloma and lymphoma and up to 178.000 new cases are diagnosed with these tumors each year. Different kinds of treatment including radiotherapy, chemotherapy, immunotherapy and stem cell transplantation have been employed in the therapy of hematological cancers. However, they are still causing death among patients. On the other hand, curcumin as an anti-cancer agent for the suppression of human cancers has been introduced. The treatment of hematological cancers using curcumin has been followed. Curcumin diminishes viability and survival rate of leukemia, myeloma and lymphoma cells. Curcumin stimulates apoptosis and G2/M arrest to impair progression of tumor. Curcumin decreases levels of matrix metalloproteinases in suppressing cancer metastasis. A number of downstream targets including VEGF, Akt and STAT3 undergo suppression by curcumin in suppressing progression of hematological cancers. Curcumin stimulates DNA damage and reduces resistance of cancer cells to irradiation. Furthermore, curcumin causes drug sensitivity of hematological tumors, especially myeloma. For targeted delivery of curcumin and improving its pharmacokinetic and anti-cancer features, nanostructures containing curcumin and other anti-cancer agents have been developed.

Keywords: Curcumin; Hematological cancers; Molecular pathway; Nanoparticles; Targeted delivery.

Graphical abstract

Fig. 1

Curcumin administration in treatment of leukemia. The apoptosis regulation by curcumin reduces tumorigenesis. Increase in cytochrome c release, upregulation of caspases and cleavage of PARP by curcumin can induce apoptosis. The curcumin derivatives have also shown potential in regulation of apoptosis and autophagy in cancer therapy. Curcumin can be employed with quercetin, canabidiol, piperine and thalidomide in treatment of leukemia. Moreover, polymeric nanoparticles and chitosan nanostructures have delivered curcumin in leukemia therapy.

Fig. 2

Curcumin use in treatment of lymphoma. The lipid-based nanoparticles are common structures for delivery of curcumin in lymphoma therapy and co-delivery with other compounds such as imatinib. Proliferation suppression and apoptosis acceleration can be obtained through application of curcumin. The upregulation of miR-98 and miR-200 and downregulation of miR-21 and miR-199 mediate the anti-cancer activity of curcumin. Upregulation of Bax and Bad, and release of cytochrome C can mediate apoptosis in tumor cells. Furthermore, cancer metastasis can be reduced due to downregulation of MMP-2 and MMP-9.

Fig. 3

Curcumin administration in treatment of myeloma. The downregulation of STAT3, Akt and Notch3 can significantly reduce the progression of tumor cells. Upregulation of p53 by curcumin induces apoptosis. Moreover, GO-Y030 and GO-Y078 s derivatives of curcumin downregulate IL-6, PI3K/Akt, STAT3 and IRF4 in suppressing tumorigenesis. Moreover, P-gp suppression by curcumin reduces chemoresistance.