World Journal of
Pharmaceutical and Life Sciences

REPURPOSING BIGUANIDE DRUG METFORMIN FOR TARGETING TNF α INDUCED EPITHELIAL MESENCHYMAL TRANSITION IN HUMAN COLORECTAL CARCINOMA

Ashwini and Rayanna

ABSTRACT

According to Global cancer statistics by world region for the year 2024 based on IA RS, Colorectal
carcinoma (CRC) is the 3 rd most prevalent cancer worldwide comprising approximately 9.6%. Various factors
influence CRC progression, including genetic mutations in the microenvironment, angiogenesis, epithelial
mesenchymal transition (EMT), and lymphatic spread. EMT is particularly significantly regulated by signaling
pathways including TNF β. TNF α, an inflammatory cytokine, has been shown to disrupt anticancer mechanisms
by promoting EMT, which remains underexplored. This study aims to inve stigate the effects of TNF α induction on
EMT in CRC and to evaluate the potential of metformin, a biguanide drug traditionally used for type 2 diabetes, as
a repurposed treatment with anticancer properties. The capacity of the HCT116 cell line, which is f requently
employed in cancer studies to express characteristics of mature intestinal studies, hence HCT116 has been used for
all our assays. Primarily, the antiproliferative effect of metformin on HCT 116 was studied by NRU assay. To
examine the impact of metformin on metastasis, TNF α was introduced to HCT116, and NRU assay was
performed. Further, cell migration, cell aggregation, clonogenic, and ROS assays were carried out for validation. In
addition to studying anti inflammatory and antimetastatic activity, ELISA and to study the tu mor pathway, qPCR
was done. Metformin showed dose dependent antiproliferative effects, inhibiting cell migration and upregulating
E cadherin. It also enhanced apoptosis Via ROS induction. Metformin also showed anti inflammatory effects,
reducing IL 1β leve ls and restoring SMAD4 expression, suppressing tumors.

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