Apoptosis-based therapies for hematologic malignancies

Abstract

Apoptosis is an intrinsic cell death program that plays critical roles in tissue homeostasis, especially in organs where high rates of daily cell production are offset by rapid cell turnover. The hematopoietic system provides numerous examples attesting to the importance of cell death mechanisms for achieving homeostatic control. Much has been learned about the mechanisms of apoptosis of lymphoid and hematopoietic cells since the seminal observation in 1980 that glucocorticoids induce DNA fragmentation and apoptosis of thymocytes and the demonstration in 1990 that depriving colony-stimulating factors from factordependent hematopoietic cells causes programmed cell death. From an understanding of the core components of the apoptosis machinery at the molecular and structural levels, many potential new therapies for leukemia and lymphoma are emerging. In this review, we introduce some of the drug discovery targets thus far identified within the core apoptotic machinery and describe some of the progress to date toward translating our growing knowledge about these targets into new therapies for cancer and leukemia. (Blood. 2005;106:408-418)

Cytotoxicity of methanol extracts of Elaeis guineensis on MCF-7 and Vero cell lines

“…Moreover, plant derived drugs like vinblastine, vincristine, taxol, and camptothecin had lead to greatest extend within the vicinity of antitumor upon where, the drugs were reported to improvise the chemotherapy of some cancers [6] . Plants contain almost unlimited capacity to generate compounds that fascinates researchers in the quest for new and novel chemotherapeutics [7] . The persistency search for new anticancer compounds in plant medicines and traditional foods is a realistic and promising strategy for its prevention [8] .…”

BCL-2 in the crosshairs: tipping the balance of life and death

“…More than a dozen small molecules and peptidic compounds are currently in preclinical and clinical development for targeting the structurally defined multidomain antiapoptotic groove 113,142 (Table 1). Preclinical development of small molecule and peptide inhibitors of proapoptotic BCL-2 family proteins is also underway.…”

Sodium arsenite accelerates TRAIL-mediated apoptosis in melanoma cells through upregulation of TRAIL-R1/R2 surface levels and downregulation of cFLIP expression

“…The impairment of apoptosis is one of the key characteristics of cancer development, which renders tumors resistant to cytotoxic therapy [2]. Consequently, anti-cancer drug discovery strategies have focused on core components of the apoptosis machinery in the cell, as main targets, in order to restore sensitivity of cancer cells to apoptosis [3]. In this respect, the use of arsenic trioxide (or sodium arsenite) as a regulator of gene expression and a stimulator of oxidative stress, which was followed by induction of programmed cell death, has been shown to be effective in the treatment of acute promyelocytic leukemia (APL) [4] and of some cases of prostate cancer [5].…”