Parthenolide Induces Oxidative Stress and Impedes Cell Migration by Suppressing Wnt Pathway and Epithelial-Mesenchymal-Transition (EMT) in HCT-116 Metastatic Colorectal Cancer Cells

Abstract

Colorectal cancer (CRC) is a vital cause of cancer morbidity and mortality. 50% of CRC patients suffer from an aggressive metastatic disease which ultimately fallout in death. In metastatic cancer, tumour cells migrate, invade, and finally colonise to the distant organ by degrading their attachments with the extracellular matrix. Parthenolide (PTL) is a secondary metabolite of feverfew (Tanacetum parthenium) plant. It shows its cytotoxic effect towards cancer cells via different cellular signalling pathways like inhibition of NF-κB, STAT3, MAPK, JNK pathways, activation of p53 etc. In the present study, we have assessed anti-cancer and anti-metastatic potential of PTL against human HCT-116 metastatic colorectal cancer cells. Analysis of cellular oxidative status (GSH/GSSG) of PTL treated HCT-116 cells showed a significant decrease (p<0.05) in GSH level while GSSG level was increased significantly (p<0.05) on PTL treatment. PTL also increased the amount of intracellular reactive oxygen species. The qRT-PCR analysis revealed that PTL down-regulates c-fos, c-jun and N-cadherin expression and up-regulates E-cadherin expression indicating inhibition of cell migration and metastasis by EMT pathway. PTL inhibited the MMP-9 expression in a dose-dependent fashion and inhibited cancer cell migration by regulating Wnt/β-catenin signalling through the up-regulation of DKK-1 protein expression indicating PTL has a promising anti-cancer potential against HCT-116 metastatic colorectal carcinoma cells.

Degradable Polymer-Based Nanoassemblies for Precise Targeting and Drug Delivery to Breast Cancer Cells without Affecting Normal Healthy Cells

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“…Images were captured in an Olympus IX71 microscope at 100× magnification. Respective scratch areas were measured thrice using ImageJ software …”

“…The cell viability percentage was calculated with respect to the control. 75 2.21. Cellular Morphology Study.…”

“…Respective scratch areas were measured thrice using ImageJ software. 75 2.23. Mammosphere Inhibition Assay.…”

Poly-β-thioester-Based Cross-Linked Nanocarrier for Cancer Cell Selectivity over Normal Cells and Cellular Apoptosis by Triggered Release of Parthenolide, an Anticancer Drug

“…Here, we have used this system as a potential drug carrier for sesquiterpene lactone-based anticancer agent parthenolide (PTL). Sesquiterpene lactones are secondary metabolites isolated from plants of the Asteraceae family, Tanacetum parthenium, and have been used to treat certain ailments traditionally. , The natural ingredient parthenolide (PTL) is one of the active sesquiterpene lactones of this plant. PTL has shown cytotoxicity or induced apoptosis in various cancer cells via different cellular signaling pathways, viz., inhibition of NFκB, MAPK, JNK, and STAT3 pathways, activation of apoptosis by p53, suppression of nucleic acid biosynthesis pathway, depletion of intercellular thiols, induction of oxidative stress, promotion of mitochondrial dysfunction, interference of cellular calcium homeostasis, cell cycle arrest, depletion of HDAC1, and inhibition of tubulin carboxypeptidase activity .…”