Anticancer Effects of Cucurbitacin B and Meleagrin Associated with TYRO3 Downregulation in Colorectal Cancer Cells

Area of Science:

• Oncology
• Molecular Biology
• Natural Products Chemistry

Background:

• Colorectal cancer (CRC) is a leading cause of cancer mortality globally.
• There is a critical need for novel molecular targets and therapeutic strategies for CRC.
• TYRO3, a TAM receptor tyrosine kinase, is implicated in CRC progression and poor prognosis.

Purpose of the Study:

• To investigate the effects of natural compounds Meleagrin and Cucurbitacin B on TYRO3 expression.
• To evaluate the impact of these compounds on colorectal cancer cell behavior, including proliferation, apoptosis, and migration.
• To assess the potential therapeutic utility of these compounds in CRC treatment.

Main Methods:

• Utilized HCT-116 and HT-29 colorectal cancer cell lines.
• Assessed cell proliferation, apoptosis, and migration using functional assays.
• Quantified TYRO3 expression levels through expression-based analyses.
• Included normal colon epithelial cells (CCD 841 CoN) for selectivity assessment.

Main Results:

• Both Meleagrin and Cucurbitacin B modulated TYRO3 expression in CRC cells.
• Both compounds significantly suppressed CRC cell proliferation and wound closure (migration).
• Cucurbitacin B demonstrated stronger antiproliferative and pro-apoptotic effects.
• Meleagrin exhibited antiproliferative activity with notable selectivity, showing lesser effects on normal colon cells.

Conclusions:

• Meleagrin and Cucurbitacin B show promise as agents targeting TYRO3 in colorectal cancer.
• Meleagrin's potential selectivity profile warrants further investigation for therapeutic applications.
• These natural compounds represent potential candidates for further mechanistic studies and development in CRC therapy.