AI Article Synopsis
- Malignant glioma is a highly lethal brain cancer with few treatment options, prompting research into new therapies like LTr1, derived from cruciferous vegetables.* -
- LTr1 showed strong anti-glioma effects in various human glioma cell lines and effectively reduced tumor growth in a mouse model.* -
- The compound works by binding to TrkA, inhibiting its activity and affecting the PI3K/AKT pathway, leading to cell cycle arrest and increased cancer cell death, while also crossing the blood-brain barrier.*
Article Abstract
Malignant glioma is the most fatal, invasive brain cancer with limited treatment options. Our previous studies show that 2-(indol-3-ylmethyl)-3,3'-diindolylmethane (LTr1), a major metabolite of indole-3-carbinol (I3C) derived from cruciferous vegetables, produces anti-tumour effect against various tumour cell lines. In this study we characterized LTr1 as a novel anti-glioma agent. Based on screening 134 natural compounds and comparing the candidates' efficacy and toxicity, LTr1 was selected as the lead compound. We showed that LTr1 potently inhibited the viability of human glioma cell lines (SHG-44, U87, and U251) with IC values of 1.97, 1.84, and 2.03 μM, respectively. Furthermore, administration of LTr1 (100,300 mg· kg ·d, i.g. for 18 days) dose-dependently suppressed the tumour growth in a U87 xenograft nude mouse model. We demonstrated that LTr1 directly bound with TrkA to inhibit its kinase activity and the downstream PI3K/AKT pathway thus inducing significant S-phase cell cycle arrest and apoptosis in SHG-44 and U87 cells by activating the mitochondrial pathway and inducing the production of reactive oxygen species (ROS). Importantly, LTr1 could cross the blood-brain barrier to achieve the therapeutic concentration in the brain. Taken together, LTr1 is a safe and promising therapeutic agent against glioma through inhibiting TrkA/PI3K/AKT pathway.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10203337 | PMC |
| http://dx.doi.org/10.1038/s41401-022-01033-y | DOI Listing |
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