Study of growth property of complement C2 produced by THP-1 cells using the chemical agents –Histamine, Imidazole and β- Glycyrrhetinic acid

ABSTRACT:

Despite significant research on the role of inflammation and immunosurveillance in the immunologic microenvironment of cancer, little attention has been given to the oncogenic capabilities of the complement cascade. The complement system is the major branch of the humoral immune system.  Complement components C2 and factor B are essential for the classical and alternative pathways of complement activation, respectively, because they provide catalytic subunits for the C3 and C5 convertases, both of which are key enzymes for the complement system. Monocytes and macrophages synthesize complement proteins, thus providing an essential local source of these proteins in vivo which serve as a first-line host defense mechanism. The recent findings have shown that complement factor especially Factor B and C2 facilitates cellular proliferation and regeneration. We address this hypothesis using chemical agents Histamine, Imidazole and β- Glycyrrhetinic acid who individually influence the factor C2 production in THP-1 cells (human monocytic leukemia cell line). We investigated the growth property of complement C2 by studying the effect of these three chemical agents on the growth of THP-1 cells in time and concentration dependent manner. In this study, to our knowledge we have shown that the Complement C2 has a proliferating effect on monocytic leukemia cells. Additionally, the results show that these three chemical agents do have an influence on each other’s growth properties. Given that the traditionally held functions for the complement system include innate immunity and cancer defense, our study suggests a new way of thinking about the role of complement proteins in monocytes especially human monocytic leukemia. These results may give us leads for the treatment of monocytic leukaemias like AML-M5 which are difficult to treat.

Key words: Cancer, Complement C2, Factor B, Histamine, Imidazole and β- Glycyrrhetinic acid, THP-1, AML-M5.

For the whole article click on the link below:

https://docs.google.com/open?id=0BzdHWb7McaBDRG0tNmNFTGg2Tzg 

Differentiation Therapy and AML

Abstract:

Acute myelocytic leukaemia (AML) is a clonal disorder that is the consequence of acquired somatic mutations in hematopoietic progenitor cells that block normal differentiation and cell death and confer a proliferative growth advantage (Wang R. et. al., 2006). AML is basically a group of malignant bone marrow neoplasms of myeloid precursors of white blood cells.

The symptoms can be aspecific: asthenia, pallor, fever, dizziness and respiratory symptoms. Diagnostic methods include blood analysis, bone marrow aspirate for cytochemical, immunological and cytogenetical analysis, and cerebrospinal fliud (CSF) investigations. Treatment includes intensive multidrug chemotherapy and in selected cases allogenic bone marrow transplantation. Nevertheless, outcome of AML remains poor with overall survival of 35-60%. New therapeutics are required to increase the probability of cure in this serious disorder (Verschuur A. C. et. al., 2004).

Differentiation therapy has been successful as a novel treatment for APL. Several compounds including dimethyl sulfoxide, retinoic acid, phorbol ester and 1, 25-dihydroxy vitamin D3 induce AML cells to differentiate toward mature cells. Among them, retinoic acid induces AML cells to differentiate toward granulocytes, whereas 1, 25-dihydroxy vitamin D3 induces AML cells to differentiate toward monocytes (Hyun-Ock Pae a,b et. al., 2001). The following is the overview of advancement in Differentiation therapy against AML specifically AML-M5.

Key words:
AML, Hematopoietic, Symptoms, Daignostic, Therapeutics, Differentiation Therapy.

For full review click on the link below:
https://docs.google.com/open?id=0BzdHWb7McaBDM3VZMEdMS3pSdm1TSEJJbzc5UVNCUQ