Oral supplementation with honokiol effective against human thyroid cancer in xenograft mouse model

In the United States it is estimated that in 2016 approximately 64,000 new patients will be diagnosed with thyroid cancer (for perspective – that compares to 240,000 patients with breast cancer and 135,000 patients with colon cancer). Approximately 2000 patients die of thyroid cancer each year. Approximately 600,000 patients were living with thyroid cancer in the United States in 2013. Thyroid cancer is often treatable and cured with surgery and radioactive iodine.

Three clinical pathological types of thyroid cancers have been identified: differentiated thyroid cancer (DTC), poorly differentiated thyroid cancer (PDTC) and andanaplastic thyroid cancer (ATC). Follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC) are also classified as within DTCs. Patients with DTC typically become disease-free after treatment. However 10%–15% of them have recurrent disease. Cases of ATC and PDTC are rare, but are aggressive and the least likely to respond to current available chemotherapeutic agents or radiotherapy with possible lethal outcome.

With this as background a team of researchers from Taiwan turned to honokiol which has demonstrated anti-cancer properties against various cancers. Honokiol is a lignan isolated from the bark, seed cones, and leaves of trees belonging to the genus Magnolia. Its widely cultivated in Asian countries such as China, Japan, and Korea.

The researchers carried out in-vitro tests with cultures of human ATC (ARO), FTC (WRO) cell lines and PDTC cell lines (SW579). After incubation with honokiol, reduction of cell viability was found in the ARO, WRO, and SW579 cells, suggesting that honokiol may be effective against human thyroid cancers. Detailed further testing found significantly increased G0/G1 cell cycle arrest in the ARO and WRO cells but only marginally increased G0/G1 cell cycle arrest in the SW579 cells (the control of cell cycle progression in cancer cells is considered an effective strategy for controlling cancer growth). The honokiol-treated SW579 cells did however show increased susceptibility to cell death. The researchers in addition concluded that honokiol induces caspase-dependent apoptosis and autophagy with the underlying mechanism mediated, at least partially, by the downregulation of PI3 K/Akt and MAPK pathways. The in-vitro testing results together indicate that honokiol is an anticancer agent for human ATC, FTC, and PDTC cells but that the underlying mechanisms of anticancer activity differ in each.

For the xenograft mouse model in vivo experiment six-week old female mice were randomized into three groups. The aggressive and poorly treatable anaplastic thyroid carcinoma cells (ARO cell line), were injected into the mice at day 0. Ten days after injection, when the tumor size was still less 1mm3, the mice were treated with either DMSO (control substance) or honokiol (supplementation at 5 or 15 mg/kg) every 3 days for 3 weeks. At the end of the three weeks the tumors in the control group and the honokiol treatment group were compared. In the control group the average tumor weight was 700mg, in the 5mg/kg honokiol treatment group 400mg and in the 15mg/kg honokiol treatment group the tumor weight was 200mg (=72% less than the control group).

Using FDA specified guidelines we can calculate the Human Equivalent Dose (HED). The higher 15mg/kg/day dosing given to the mice translates in approx. 1,2mg/kg/day for humans. Or approximately a 84mg daily honokiol dose for a person weighing 70kg. Typical supplements on the market have serving sizes of 200mg magnolia bark extract out of which 90% honokiol (180mg). Toxicity studies indicate honokiol is likely safe till gram level.

These results, combined with the realistic dosing levels, indicate that honokiol clearly has potential for development into a therapeutic option for thyroid cancer. Combined with the other anti-cancer and health properties it also strengthens the case of honokiol being part of a cancer preventative supplementation stack. The author of the article takes it on daily basis. You can find the study here.

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