The Effect of NF-κB Deactivation on Cancer Cell Response to ALA Mediated Photodynamic Therapy.

OBJECTIVE: Breast cancer is one of the most widespread tumors among women worldwide, which is difficult to treat due to the presence of chemoresistance and the risk of tumor recurrence and metastasis. There is a pressing necessity to develop efficient treatments to improve response for treatment and increase prolong survival of breast cancer patients. Photodynamic therapy (PDT) has attracted interest for its features as a noninvasive and relatively selective cancer treatment. This method relies on light-activated photosensitizers that, upon absorbing light, generate reactive oxygen species (ROS) with powerful cell-killing outcomes. Nuclear factor kappa B (NF-κB), a transcription factor, plays a key role in cancer development by regulating cell proliferation, differentiation, and survival. Inhibiting NF-κB can sensitize tumor cells to chemotherapeutic agents. Dimethyl fumarate (DMF), an NF-κB inhibitor approved by the FDA for multiple sclerosis treatment, has further shown promise in suppressing breast cancer cell growth in vitro. We hypothesized that combining PDT with Dimethyl fumarate (DMF) could further enhance therapeutic efficacy for both treatment modalities. METHODS: In the current study, we explored the PDT effect of 1 and 2 mM aminolaevulinic acid (ALA) and low-power He-Ne laser irradiation combined with different concentrations of DMF (2.5, 1.25, or 0.652 µg/ml) against hormone nonresponsive AMJ13 breast cancer cell line that is derived from Iraqi patient. RESULTS: Our results demonstrated that co-administration with all tested DMF concentrations significantly enhanced the cytotoxicity of PDT antitumor effect. The combination index analysis showed presence of synergism in combining PDT with DMF. CONCLUSION: This finding suggests that the combination of PDT with DMF could be a promising novel strategy against triple negative breast cancer that could be applied clinically due to the fact that both of these treatments are already clinically approved therapies.

3-Dimensional coculture of breast cancer cell lines with adipose tissue-Derived stem cells reveals the efficiency of oncolytic Newcastle disease virus infection via labeling technology.

Oncolytic virotherapy is one of the emerging biological therapeutics that needs a more efficient in vitro tumor model to overcome the two-dimensional (2D) monolayer tumor cell culture model's inability to maintain tissue-specific structure. This is to offer significant prognostic preclinical assessment findings. One of the best models that can mimic the in vivo model in vitro are the three-dimensional (3D) tumor-normal cell coculture systems, which can be employed in preclinical oncolytic virus therapeutics. Thus, we developed our 3D coculture system in vitro using two types of breast cancer cell lines showing different receptor statuses cocultured with adipose tissue-derived mesenchymal stem cells. The cells were cultured in a floater tissue culture plate to allow spheroids formation, and then the spheroids were collected and transferred to a scaffold spheroids dish. These 3D culture systems were used to evaluate oncolytic Newcastle disease virus AMHA1 strain infectivity and antitumor activity using a tracking system of the Newcastle disease virus (NDV) labeled with fluorescent PKH67 linker to follow the virus entry into target cells. This provides evidence that the NDV AMHA1 strain is an efficient oncolytic agent. The fluorescently detected virus particles showed high intensity in both coculture spheres. Strategies for chemically introducing fluorescent dyes into NDV particles extract quantitative information from the infected cancer models. In conclusion, the results indicate that the NDV AMHA1 strain efficiently replicates and induces an antitumor effect in cancer-normal 3D coculture systems, indicating efficient clinical outcomes.