Honokiol slows malignant brain tumor growth by killing tumor cells in preclinical testing

The symptoms, prognosis, and treatment of a malignant glioma depends on the person’s age, the exact type of tumor and the location of the brain tumor within the brain. These tumors tend to grow and infiltrate into the normal brain tissue, which makes surgical removal very difficult — or sometimes impossible — and complicates treatment. Other treatments include radiation and chemo therapy. The prognosis for these fast-growing tumors is poor.

Better standalone and complementary therapies are therefore required. In this study, the researchers evaluated the preclinical effects of honokiol on the development of malignant glioma. They examined this in-vitro and in an in-vivo mouse model.

In-vitro treatment of tumor cells with the lowest test concentration of 10 μM honokiol for 72h did not affect the tumor cell viability. However when the administered concentrations reached 20, 40, 80, and 100 μM, honokiol caused significant 23%, 34%, 83% and 91% decreases in cell viability. In addition, exposure to 40 μM honokiol for different time periods 24, 48 and 72h showed reduction of cell viability by 18%, 31% and 42%. The exposure to 20, 40, 80, and 100 μM honokiol induced 5%, 33%, 60%, and 77% cell apoptosis. Honokiol did not trigger cell necrosis. Treatment of tumor cells with 40 μM honokiol for 48h and 72h respectively induced 16% and 32% cell apoptosis again without influencing cell necrosis. In depth analyses showed that honokiol achieved the observed apoptosis and cell cycle arrest in tumor cells through activating a p53/cyclin D1/CDK6/CDK4/E2F1-dependent pathway.

The research also tested the in vivo efficacy of honokiol in a mouse brain tumor model. These mice were injected with 20 mg/kg honokiol two times per week for 2 weeks. At the end of the experiment, the survival rate of the mice was analyzed. Median survival times of mice treated with placebo and honokiol were 30 and 36 days respectively, for the type of tumor this is a significant increase in the survival rate of mice. The exposure to honokiol induced G0/G1 cell cycle arrest and apoptosis which suppressed the growth of glioma cells and prolonged the survival of tumor bearing mice. As to the mechanisms it was found that administration of honokiol decreased levels of pro-caspase-3 and increased the level of cleaved caspase-3 in the brain tumors. In addition, administration of honokiol increased protein levels of p-p53, p53, and p21. The expression levels of cell cycle-related proteins CDK6, CDK4, cyclin D1, p-RB, and E2F1 all decreased with treatment, whereas the level of the RB protein increased. The RB protein is a key regulator of cell cycle progression. The activity of the RB protein is reported to alter the response of chemotherapeutics against human non-small cell lung cancer cell lines. Loss of the RB protein’s function leads to deregulation of cell cycle control and chemo sensitivity.

Overall this study showed that honokiol decreased the viability of brain tumor cells through inducing cell cycle arrest and apoptosis. In the in-vivo brain tumor model, honokiol prolonged the survival rate of mice with brain tumors. Taken together, this study showed that honokiol possesses anticancer effects against brain tumor cells and has potential to be part of a patient treatment strategy.

One thought on “Honokiol slows malignant brain tumor growth by killing tumor cells in preclinical testing

  • March 28, 2017 at 10:38 pm
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    With The lowest test concentration of 10uM honokiol for 72h did not affect the tumor cell viability. However, when the administered concentration reached 20, 40, 80, and 100 uM, honokiol caused significant 23%, 34%, 83%, and 91% decreases in cell viability. In addition, exposure to 40 uM honokiol for 24, 48 and 72h showed reduction of cell viability by 18%, 31%, and 42%. The exposure to 20, 40, 80, and 100 uM honokiol induced 5%, 33%, 60%, and 77% cell apoptosis. Treatment of tumor cells with 40 uM honokiol for 48h and 72h reszpectively induced 16% and 32% cell apoptosis without influencing cell necrosis. Honokiol did not trigger cell necrosis. Honokil achieved the observed apoptosis and cell cycle arrest in tumor cells through activating a p53/cyclin D1/CDK6/CDK4/E2F1 – dependant pathway.

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