Amygdalin-Nano Enhanced Chemo‑ and Radiosensitivity by Targeting P38/MAPK/ immunemodulators Signaling in Breast Cancer Cells

Full text follows: Breast cancer (BC) is among the main risks to women's health worldwide is breast cancer (BC). Breast cancer (BC) cells often develop multiple mechanisms of chemo- and radio-resistance during tumor progression, which is the primary reason for the failure of breast cancer therapy. Doxorubicin, an anthracycline antibiotic, is one of the commonly prescribed chemotherapeutic agents against a broad spectrum of cancers, including breast cancer. However, the clinical efficacy and usefulness of doxorubicin-based treatment regimens are still limited because of dose-limiting toxicity and induction of drug resistance. Therefore, there is an urgent need to develop new sensitizing agents that enhance the efficacy of Doxorubicin and circumvent chemoresistance. Targeted nanomedicines have tremendous therapeutic potential in BC treatment over their free drug counterparts. This study aims to evaluate and compare the chemo- and radio-sensitizers efficacy of amygdalin-folic acid-nanoparticles (AFA) on MCF-7 and MDA-MB-231 cells. The effects of AFA on MCF-7 and MDA-MB-231 cell proliferation and IC50 were assessed using MTT. The expression of proteins involved in several mechanisms induced by AFA in MCF-7 and MDA-MB-231 cells, including growth inhibition, apoptosis, tumor growth regulators, immune-modulators, and chemo‑ and radio‑sensitizing activities of AFA on MCF-7 and MDA-MB-231 cells were evaluated via and flow cytometry and Elisa. The results indicated that AFA inhibited proliferation, promoted apoptosis cell cycle arrest, and suppressed tumor promotion in MCF-7 and MDA-MB-231 cells in a dose‑dependent manner. AFA treatment also induced the mitogen-activated protein kinases-downregulation protein kinase (MAPK/P38) with a concomitant reduction in the expression of tumor promoters signaling, including CD4, CD80, TGF-β, and Fe. In addition, AFA enhanced the chemosensitivity of MCF-7 and MDA-MB-231 cells to Doxorubicin. A combination of AFA and radiation enhanced apoptosis and increased the expression of two radiations‑induced DNA damage markers, CD8 and ROS. In conclusion, the present results demonstrated that AFA, a targeted compound, could suppress the proliferation of breast cancer cells, reduce the expression of tumor promotion‑related proteins, and enhance the chemo‑ and radio‑sensitivity of MCF-7 and MDA-MB-231 cells by targeting P38/MAPK/immunomodulators signaling.