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Isolinderalactone Induces Apoptosis, Autophagy, Cell Cycle Arrest and MAPK Activation through ROS-Mediated Signaling in Colorectal Cancer Cell Lines

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Isolinderalactone (ILL), a sesquiterpene isolated from the root extract of Lindera aggregata, has been reported to exhibit anti-proliferative and anti-metastatic activities in various cancer cell lines. However, the mechanisms associated with its antitumor effects on CRC cells remain unclear. ILL treatment significantly suppressed proliferation and induced cell cycle G2/M arrest in CRC cells by inhibiting the expression of cyclin B, p-cdc2, and p-cdc25c and up-regulating the expression of p21. In addition, ILL induced mitochondria-associated apoptosis through the up-regulation of cleaved -caspase-9 and -3 expression. ILL induced autophagy by increasing the levels of LC3B in CRC cells, which was partially rescued by treatment with an autophagy inhibitor (chloroquine). Furthermore, ILL increases the accumulation of reactive oxygen species (ROS) and activates the MAPK pathway. Application of the ROS scavenger, N-acetyl cysteine (NAC), effectively inhibited ILL toxicity and reversed ILL-induced apoptosis, cell cycle arrest, autophagy, and ERK activation. Taken together, these results suggest that ILL induces G2/M phase arrest, apoptosis, and autophagy and activates the MAPK pathway via ROS-mediated signaling in human CRC cells.

 

Comments:

The findings regarding Isolinderalactone (ILL) and its impact on colorectal cancer (CRC) cells seem quite promising. ILL appears to exert multiple effects on CRC cells, affecting various pathways crucial for cell proliferation and survival.

The study indicates that ILL treatment leads to:

1. **Suppression of Proliferation**: ILL significantly inhibits the proliferation of CRC cells.

2. **Cell Cycle Regulation**: It induces G2/M phase arrest by affecting the expression of cell cycle regulators such as cyclin B, p-cdc2, p-cdc25c, and up-regulating p21, which is known to halt cell cycle progression.

3. **Apoptosis Induction**: ILL triggers mitochondria-associated apoptosis by up-regulating cleaved-caspase-9 and -3 expression, which are key markers of the apoptotic pathway.

4. **Autophagy Activation**: ILL induces autophagy, as evidenced by increased levels of LC3B. This effect can be partially inhibited by an autophagy inhibitor like chloroquine.

5. **ROS Accumulation and MAPK Pathway Activation**: ILL increases the accumulation of reactive oxygen species (ROS) and activates the MAPK pathway. ROS scavengers like N-acetyl cysteine (NAC) effectively counteract ILL-induced toxicity and reverse its effects on apoptosis, cell cycle arrest, autophagy, and ERK activation.

These results suggest that ILL's mechanism of action in CRC cells involves a complex interplay of multiple pathways. Its ability to induce cell cycle arrest, trigger apoptosis, activate autophagy, and modulate ROS levels, all of which are critical in controlling cancer cell growth and survival, makes it a potentially valuable candidate for further investigation as a therapeutic agent for colorectal cancer.

However, further studies, including in vivo experiments and clinical trials, would be essential to validate these findings and assess the safety and efficacy of ILL as a potential treatment for colorectal cancer.

Related Products

Cat.No. Product Name Information
E0011 Linderalactone Linderalactone inhibits human lung cancer growth by modulating the expression of apoptosis-related proteins (Bax and Bcl-2) with an IC50 of 15 µM in A-549 cells. Linderalactone induces G2/M cell cycle arrest and could also suppress the JAK/STAT signalling pathway. Linderalactone can be isolated from Radix linderae.

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JAK STAT Bcl-2