Our data demonstrated that IL-24 application promoted cancer death by inducing mitochondrial stress, as manifested by mitochondrial ROS overproduction, mitochondrial potential dissipation, cellular ATP deprivation and mitochondrial death activation.
Melanoma differentiation-associated gene-7/interleukin-24 (<i>mda-7/IL-24</i>) is a multifunctional cytokine displaying broad-spectrum anticancer activity in vitro or in vivo in preclinical animal cancer models and in a phase 1/2 clinical trial in patients with advanced cancers.
Interleukin-24 (IL-24) is known for its tumor suppressive activity and the selective induction of apoptosis of numerous human cancer cells, while demonstrating little harm to normal cells.
NNK exposure to niacin-deficient cells raised the expression of eight genes including genes crucial in promoting cancer such as FGFR3 and DUSP1 and suppressed the expression of 33 genes, including genes crucial in preventing the onset and progression of cancer like RASSF2, JUP, and IL24, in comparison with the cells grown in niacin-proficient medium.
We have shown that IL-24 regulates apoptosis through phosphorylated eukaryotic initiation factor 2 alpha (eIF2α) during endoplasmic reticulum (ER) stress in cancer.
Discovered in the early 1990s, MDA-7/IL-24 has proven to be a potent, near ubiquitous cancer suppressor gene capable of inducing cancer cell death through apoptosis and toxic autophagy in cancer cells in vitro and in preclinical animal models in vivo.
Melanoma differentiation associated gene-7 (MDA-7)/IL24 is a well-studied cytokine established as a therapeutic in a wide array of cancers upon delivery as a gene therapy.
We have generated a chimeric tropism-modified type 5 and 3 adenovirus that selectively replicates in cancer cells and simultaneously produces a secreted anti-cancer toxic cytokine, melanoma differentiation associated gene-7/Interleukin-24 (mda-7/IL-24), referred to as a Cancer Terminator Virus (CTV) (Ad.5/3-CTV).
Interleukin 24 (IL-24) is a tumor-suppressing protein, which has the ability to inhibit angiogenesis, sensitize cancer cells to chemotherapy, and induce cancer cell-specific apoptosis.
Overall, this study provides useful information on the potential use of engineered MSCs for the controlled secretion of therapeutic proteins, in this case MDA-7, for targeted cancer therapy.
These findings suggest that the artificially designed recombinant fusion protein TAT-IL-24-KDEL may be highly effective in cancer therapy and worthy of further evaluation and development.
Using the MMTV-PyMT spontaneous mammary tumor model, we confirmed that exogenously introducing MDA-7/IL-24 using a Cancer Terminator Virus caused a reduction in tumor burden and also produced an antitumor "bystander" effect.
Conditionally replication competent adenoviruses (Ads) that selectively replicate in cancer cells and simultaneously express a therapeutic cytokine, such as melanoma differentiation associated gene- 7/Interleukin-24 (mda-7/IL-24), a Cancer Terminator Virus (CTV-M7), hold potential for treating human cancers.
In the present study, administration of MDA-7/IL-24 by means of tumor-selective replicating adenovirus (ZD55-IL-24) was used to investigate whether ZD55-IL-24 could attenuate Nrf2-mediated oxidative stress response in cancer cell.
As research in the field progresses, we will unravel more of the functions of MDA-7/IL-24 and define novel ways to utilize MDA-7/IL-24 in the treatment of cancer.
Subtraction hybridization combined with induction of cancer cell terminal differentiation in human melanoma cells identified melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) and SARI (suppressor of AP-1, induced by IFN) that display potent antitumor activity.
Therefore, our results indicate that cancer gene therapy combining two or more tumor suppressors, such as IL-24 and OSM, may constitute a novel and effective therapeutic strategy for treating malignant melanoma and other cancers.
These bipartite CRCAs, when armed with a transgene, are called cancer terminator viruses (CTVs), i.e., Ad.PEG-E1A-CMV-mda-7 (CTV-M7) and Ad.PEG-E1A-CMV-IFN-γ (CTV-γ), because of their universal effectiveness in cancer treatment irrespective of p53/pRb/p16 or other genetic alterations in tumor cells.
This suggests that IL-24 plays a profound role in suppressing tumour lymphangiogenesis, thereby, reducing the likelihood of cancer metastasis via the lymphatic route.