| Compound/ Reagents Name |
Regulatory mechanism |
References |
| Bryostatin-1 |
It is immune modulator have ability to enhanced expression of CD20 at both mRNA and protein levels in human tumor B-cells. Moreover, the enhanced expression of CD20 was dependent of phosphorylation of MAPK kinase/ERK signal transduction pathway in association with protein kinase C, but was independent of p38MAPK and insensitive to dexamethasone. |
[111] |
| Interleukin-4 |
Interleukin-4 (IL-4) has ability to increased CD20 promoter activity and CD20 expression but modestly improved rituximab activity in RRCL and in primary B-cell lymphoma cells suggesting the existence of a defect in CD20 protein transport in RRCL. |
[106] |
| GMCSF |
Granulocyte-macrophage colony stimulating factor (GM-CSF) has been shown to enhance CD20 antigen expression, augment antibody-dependent cell-mediated cytotoxicity, and stimulate immune cell proliferation. This may lead to an improved anti-tumor effect of rituximab while reducing the severity of chemotherapy-induced myelosuppression |
[114] |
| Tumor necrosis factor-α |
TNF-α showed enhanced CD20 expression on cells from patients with B-CLLin vitro. |
[108] |
| Statins |
Statins are inhibitors of cholesterol synthesis and decreases the production of prenyltransferase groups (farnesyl and geranylgeranyl pyrophosphates) have ability to induce conformational changes in CD20 molecules and impair rituximab mediated complement dependent cytotoxicity |
[115] |
| Interferon-α |
Interferon-α has ability to directly upregulatingCD20 levels and priming may augment the effectiveness of antibody therapy. |
[116] |
| L-744,832 |
L-744,832 is most potent inhibitor of farnesyltransferase and has ability to up-regulation of CD20 levels and improved antitumor activity of anti-CD20mAbs. Moreover, it induced binding of PU.1 and Oct-2 with the CD20 promoter sequences |
[117] |
| Bortezomib |
Bortezomib is a proteasome inhibitor has ability to induced expression of COOH-terminal region but not the whole CD20 molecule. One more report revealed that prolonged (48 hours) incubation with bortezomib lead to a significant decrease in levels of CD20 on cell surface as well as R-CDC. Moreover, these effects may be partly reversed by bafilomycin A1, an inhibitor of lysosomal/autophagosomal pathway of protein degradation. |
[118,119] |
| 5-azacytidine |
5-azacytidine is inhibitor of DNA methyltransferase has ability to induced changes CD20 expression in primary B-cell lymphoma cells |
[120] |
| Trichostatin-A |
It is an inhibitor of the class I and II mammalian histone deacetylase (HDAC) families of enzymes. It has potential to regulate of both CD20 mRNA and protein levels by epigenetically in B-cell lymphoma. |
[121,122] |
| Valproic acid (VPA) and Romidepsin |
Valproic acid (VPA) and romidepsin are HDAC inhibitors have ability to increased CD20 expression mediated through hyper-acetylation and recruitment of Sp1 |
[123] |
| Radiation-induced |
Cells exposed to radiation, CD20 expression were found to be significantly higher at mRNA and protein levels in B-cell lymphoma. The levels of CD20 on cell surface associated with generation of free radicals and changes oxidative stress in cellular milieu and associated in changes Oct 1, Oct 2, PU.1, and Bob 1. Moreover, it was found that the overexpression of Bcl-2 is not inhibiting CD20 expression. |
[112,124-127] |
