A Novel Thymic Immunomodulatory Pentapeptide (TIP-5) Exhibits Anticancer Activity by Targeting the Grb2-Mediated MAPK Pathway in Breast Cancer
Muhammad Ijaz, Muhammad Shahbaz, Muhammad Inam, Fouzia Latif, Muhammad Hayat, Hizar SubthainIntroduction:
Breast cancer is the most frequently diagnosed cancer and remains one of the primary causes of cancer-related deaths among women across the globe. Grb2 plays a key role in oncogenic signaling and is frequently overexpressed in breast cancer, making it a promising therapeutic target.
Methods:
In this study, the anticancer potential of a novel thymic immunomodulatory pentapeptide (TIP-5) in breast cancer models was evaluated.
Results:
In vitro analyses demonstrated that TIP-5 markedly suppressed the proliferation of Grb2- overexpressing MCF-7 breast cancer cells in a dose- and time-dependent manner, while exerting minimal effects on Grb2-downregulated MCF10A normal breast epithelial cells. A time-dependent reduction in IC₅₀ values, accompanied by an increasing selectivity index, indicated enhanced preferential cytotoxicity toward cancer cells. In vivo experiments further confirmed the antitumor efficacy of TIP-5, with a 54% reduction in tumor growth at a dose of 25 mg/kg and no observable toxicity in major organs.
Discussion:
Mechanistic investigations revealed that TIP-5 markedly downregulated ERK expression, suggesting inhibition of the Grb2-mediated ERK/MAPK signaling pathway.
Conclusion:
Collectively, these findings suggest that TIP-5 is a potent and selective anticancer agent with promising therapeutic potential for breast cancer treatment.