Insights into Mechanisms and Promising Triple Negative Breast Cancer Therapeutic Potential for a Water-Soluble...

Area of Science:

• Oncology
• Medicinal Chemistry
• Molecular Biology

Background:

• Triple-negative breast cancer (TNBC) lacks expression of ER, PR, and HER2, limiting therapeutic options and leading to poor outcomes.
• Existing treatments for TNBC are insufficient, highlighting the need for novel therapeutic strategies.
• Previous studies showed the efficacy of the organometallic compound Ru-IM in a TNBC mouse model.

Purpose of the Study:

• To investigate the mitochondrial alterations induced by Ru-IM in TNBC cells.
• To elucidate the inhibitory effects of Ru-IM on the PI3K/AKT/mTOR pathway.
• To evaluate the in vivo efficacy of Ru-IM, alone and in combination with Olaparib, in a TNBC xenograft model.

Main Methods:

• Treatment of MDA-MB-231 cells and a TNBC mouse xenograft model with Ru-IM.
• Analysis of mitochondrial alterations and PI3K/AKT/mTOR pathway activity.
• Assessment of tumor volume, histopathology, and immunohistochemical markers (CD31, cleaved caspase 3, p-mTOR).

Main Results:

• Ru-IM treatment led to significant tumor shrinkage (59%) in the TNBC xenograft model, with combination therapy showing 65% shrinkage.
• Histopathological analysis revealed no treatment-related toxicity.
• Immunohistochemistry confirmed inhibition of angiogenesis (CD31), increased apoptosis (cleaved caspase 3), and partial inhibition of p-mTOR.

Conclusions:

• Ru-IM demonstrates significant anti-cancer effects in vitro and in vivo by targeting key cancer hallmarks and the PI3K/AKT/mTOR pathway.
• Ru-IM exhibits substantial tumor reduction efficacy in TNBC models with a favorable safety profile.
• The findings underscore the therapeutic potential of Ru-IM for treating triple-negative breast cancer.