Table 1.
Cleavage of MLL by bioflavonoids and chemotherapeutic drugs
| Name | Origin | Group | in vivo MLL cleavage (μM) | in vitro topo II inhibition |
|---|---|---|---|---|
| Flavone | H | Flavone | 200 | +/− |
| Luteolin | C,R | Flavone | 50 | ++ |
| Apigenin | C,R | Flavone | 100 | ++ |
| Baicalein | H,T | Flavone | 100 | + |
| Rutin* | C,A | Flavone | (200 = 50%) | − |
| Acacetin† | C | Flavone | — | − |
| Fisetin | H | Flavonol | 25 | ++ |
| Kaempferol | C,B | Flavonol | 100 | + |
| Myricetin | B,T | Flavonol | 100 | ++ |
| Quercetin | B,C,A,R | Flavonol | 25 | ++ |
| Quercitrin* | B,C,A,R | Flavonol | — | − |
| Quercetin-co. | D | Flavonol etc. | 25 | ++ |
| Naringenin | C | Flavanone | — | − |
| Naringin* | C | Flavanone | — | − |
| Hesperidin* | C | Flavanone | — | +/− |
| Hesperetin† | C | Flavanone | — | − |
| Taxifolin | C | Flavanol | (200 = 50%) | +/− |
| Genistein | S | Isoflavone | 50 | ++ |
| Genistin* | S | Isoflavone | 100 | + |
| Daidzein | S | Isoflavone | (200 = 50%) | + |
| BiochaninA† | S | Isoflavone | — | − |
| Quer+Fis+Gen | 10 + 10 + 10 | ND | ||
| Quer+VP16 | 10 + 10 | ND | ||
| VP16 | Epipodophyllotoxin | 25 | ++ | |
| Doxorubicin | Anthracycline | 5 | ++ | |
| Ascorbic acid | — | − | ||
| Bromelain | — | − |
The compounds tested are grouped as bioflavonoids, chemotherapeutic (chemo) drugs, or controls. From left to right the first column represents the bioflavonoid common names (*, glycosylated; †, methylated; Que, quercetin; Fis, fisetin; Gen, genistein; Quercetin complex (co), commercially available dietary supplement), and the second column represents some of the main sources of the bioflavonoids (H, herbs; C, citrus; R, root vegetables; T, teas; A, apples; B, berries; D, dietary supplements. The third column states the bioflavonoid group name, and the fourth column represents the bioflavonoid concentration in vivo, which produces the level of MLL BCR cleavage equal to 25 μM VP16 (in bold) after exposure of BV173 cells and primary hematopoietic progenitor cells to the compounds. After hybridization with the MLL BCR cDNA probe, the MLL DNA fragments (8.3 kb germline and the two MLL cleavage products 7.0 kb and 1.3 kb) were analyzed by densitometry. The concentration of each bioflavonoid that produced MLL breakage similar (±5%) to 25 μM VP16 was determined. Note that 200 μM rutin induced only 50% MLL cleavage compared to cells treated with 25 μM VP16. The fifth column represents topo II inhibition in vitro using negative supercoiled plasmid DNA or catenated kinetoplast DNA and purified human topo II: ++, topo II-dependent cleavage activity similar to VP16 or Dox; +, 50% inhibition; +/−, 10–20% inhibition; −, no inhibition. We also defined the BV173 cell line using a FACS and determined this cell line to be a T/B-lymphoid precursor. Our FACS analysis identified 92% viable BV173 cells as: 86% CD71+/38+ and CD71+/38+/10+ but negative for CD45/45RO and CD45RA.