To Evaluate the Role of Chenopodium album and Caralluma tuberculata extracts in Chronic Myeloid Leukemia

Abstract

Leukemia refers is the cancer of white blood cells (WBCs) in which aberrant proliferation of immature blasts is seen due to the differentiation blockage, hence affecting the production of normal WBCs, Leukemia can either be myeloid or lymphoid in origin and in either instance may be acute or chronic. Chronic Myeloid Leukemia is distinguished by an overabundance of differentiated and functional myeloid cells, with more aggressive subtypes containing the BCR-ABL fusion gene or Philadelphia Chromosome. Chenopodium album and Caralluma tuberculata are cacti species quite common in Asia and other regions of the world and have been involved in medicinal purposes for hundreds of years. Recently, the anti-proliferative role of both plant species and their individual constituents has been reported against solid tumors, though the effect of either species against liquid cancers remains unknown. The current study evaluated the anti-proliferative activity of both plant extracts and on K562, a BCR/ABL+ CML cell line. Cells were incubated at 37°C and 5% CO2 concentration before being treated with C. album and C. tuberculata extracts. Cell viability assay was performed to evaluate their anti-proliferative properties against K562 and other leukemic subtypes. Each extract’s anti-proliferative properties were also compared against that of imatinib, a tyrosine kinase inhibitor, in K562. Combined effect of each extract with imatinib was also assessed. Moreover, the effect of C. album and C. tuberculata extracts on the expression of c-Myc and Eya3, as well as tumor suppressor genes (p16, p21 and p53) in K562 cells was examined via qPCR. Lastly, DNA fragmentation assay was performed to identify potential apoptotic properties of each extract. Both C. album and C. tuberculata extracts showed anti-proliferative effects against K562 cells, which were comparable to those induced by imatinib. The extracts also Abstract 2 displayed an additive effect when given in combined treatment with imatinib. Expression analysis indicates slight downregulation of Eya3 by both the extracts, though c-Myc showed considerable downregulation in tumor cells when treated with C. album and more notably with C. tuberculata. Upregulation of p16 was observed in K562 treated with C. album, while both extracts induced upregulation in p21 and p53. Fragmentation assay yielded negative results, indicating that neither extract exhibited anti-apoptotic properties within the cells. Taken together, these results demonstrate an anti-proliferative role of C. album and C. tuberculata against BCR-ABL positive CML.