Apoptotic tumor cells

Kotera Y, Shimizu K, Mule JJ (2001) Comparative analysis of necrotic and apoptotic tumor cells as a source of antigen(s) in dendritic cell-based immunization. Cancer Res 61 8105 8109... 

A substantial amount of indirect evidence supports the contention that the induction of apoptosis in tumor cells is critical to successful therapy. Cancer therapy might therefore be viewed as an attempt to induce apoptosis in a population of cells that have undergone selection for apoptotic defects. If correct, this hypothesis would suggest why cancer therapy is in many cases unsuccessful. However, recent studies indicate that this fundamental problem can be circumvented. Progress in the identification of molecules key to the cell death pathways has led to a growing understanding of how apoptosis occurs [3]. It has become clear that pathways to apoptosis are numerous and often interconnected. A solution to the clinical problem of therapeutic resistance, then, may lie in the fact that there appears to be multiple ways that a cell death program can be implemented. 

Burton PBJ, Raff MC, Kerr P, Yacoub MH, Barton PJR 1999 An intrinsic timer that controls cell-cycle withdrawal in cultured cardiac myocytes. Dev Biol 216 659—670 Chen X, Ko LJ, Jayaraman L, Prives C 1996 p53 levels, functional domains, and DNA damage determine the extent of the apoptotic response of tumor cells. Genes Dev 10 2438—2451 Duesbery NS, Choi T, Brown KD et al 1997 CENP-E is an essential kinetochore motor in maturing oocytes and is masked during mos-dependent cell cycle arrest at metaphase II. Proc Natl Acad Sci USA 94 9165-9170... 

The involvement of mitochondria in the pro-apoptotic effects of carotenoids has been clearly demonstrated by the fact that P-carotene induces the release of cytochrome c from mitochondria and alters the mitochondrial membrane potential (Aym) in different tumor cells (Palozza et al., 2003a). Moreover, the highly polar xanthophyll neoxanthin has been reported to induce apoptosis in colon cancer cells by a mechanism that involves its accumulation into the mitochondria and a consequent loss of mitochondrial transmembrane potential and releas of cytochrome c and apoptosis-inducing factor (Terasaki et al., 2007). 

As described in several monographs [4], bryostatin 1 exhibits significant in vitro and in vivo antineoplastic activity against a range of tumor cell lines including murine leukemia, B-cell lymphoma, reticulum cell sarcoma, ovarian carcinoma, and melanoma. It is also effective in the modulation of apoptotic function [5], the reversal of multidrug resistance [6], and stimulation of the immune system [7]. These unique features displayed by bryostatin 1 are attributed to its high affinity for protein kinase C (PKC) isozymes and its ability to selectively modulate their functions [8]. PKCs are a type of intracellular serine and threonine kinase that... 

Inhibition of IGF-IR autophosphorylation by NVP-ADW742 results in a plethora of pro-apoptotic molecular events that may account for its effectiveness as a single agent and in enhancing the antitumor activity of a broad spectrum of chemotherapeutic and anticancer targeted agents. Initial in vivo proof-of-concept of the potential therapeutic benefit of blocking IGF-IR kinase activity in tumor cells was obtained in an orthotopic multiple myeloma (MM) model of bone and bone marrow disease. In this mice model, MM... 

Although taxanes bind to p-tubulin promoting microtubule polymerization and stabilization of the spindle complex, they serve to cause a sustained mitotic block at the metaphase/anaphase boundary. This block will occur at a lower concentration than that which is required to increase the microtubule mass (10). However, it is not completely clear how this interaction with microtubules translates into cell death. Morphologic features and the characteristic DNA fragmentation patterns seen in the setting of apoptosis have been documented in tumor cells after therapy with taxanes (10). These observations are accompanied by the phosphorylation of Bcl-2, an anti-apoptotic protein, changing the cellular balance between Bax and Bcl-2 to a status that favors apoptosis (11). 

Massive loss of tumor cells though the apoptotic pathway was restricted to the perivascular region. 

These same authors also report a dose-dependent increase in the apoptotic rate after the administration of gemcitabine (33), which they believe correlates with the elimination of the more radioresistant S phase population of cells and redistribution of the remaining cells into more radiosensitive compartments of the cell cycle. They also report in another study that reoxygenation of the resistant hypoxic fraction of tumor cells is also a mechanism for the action of gemcitabine (34). Therefore, elimination of these S phase tumor cells may aid the radiation response by not only causing cell cycle synchronization but also by leading to reoxygenation of hypoxic cells. 

---