The Bystander Effect

Although the bystander effect through GJPs may be a problem in metastasis of cancer and also the spread of cellular damage in ischemic conditions, the process may provide ways for therapies in suicide gene therapy, chemotherapy and radiotherapy. These treatments utilize the nature of the bystander effect to deliver either lethal genes, anticancer agents or ionizing radiation to local carcinogenic cells and the cells neighboring them. With the growing understanding of the bystander effect, lower dosages of agents can be used to spare healthy unaffected cells.

In suicide gene therapy, the main objective is to induce apoptosis in diseased cells. By utilizing GJIC, “death” gene signals will be able to be transmitted from the target cell to neighboring

IP3 may be involved in the release of Ca2+ from ER.

The surge of increased intracellular Ca2+ levels will pass through the GJC to adjacent neighboring cells. This surge of Ca2+ is one trigger for proceeding towards apoptosis.

IP3 itself can also pass through the GJP and trigger even more Ca2+ release from the adjacent Ca2+ reserves.

Apoptotic signals can also trigger the release of Cytochrome c from the mitochondria, which binds to the IP3R to prevent Ca2+-dependent inhibition of the receptor. This allows the ER to continue the release of Ca2+. During ischemia, Cytochrome c and other ROS will be increased in production. Since the release of ROS is one of many signals for apoptosis, antioxidants like MnSOD are effective in reversing the damage from the ROS.

The continuous release of Ca2+ from the reverses will provide a positive feedback to generate more cytochrome c and the spread of apoptotic signals. cAMP can be increased in production with inducing agents. The increased flux of cAMP will disrupt the cell cycle as it spreads from one cell to another through GJC. The increase of cAMP in the cell will promote the phosphorylation of PKA. Both increase in cAMP and activation of PKA will prolong and delayed cell growth, which may lead to

Its role is to convert arachidonic acid to prostaglandin H2 (PGH2). In the case of cancer, COX2 is upregulated and promotes the conversion of PGH2 to prostaglandin E2 (PGE2). PGE2 stimulates the release and accumulation of -catenin in the cytoplasm, which causes an imbalance. As -catenin accumulates and enters the nucleus, it activates different genes that promotes cell survival, proliferation, and angiogenesis. Hence, the upregulation of COX2 promotes tumor cells growth and also stimulates the progression to later stages of