Thyroid cancer : honokiol could be a solution

The thyroid a part of the endocrine system

The thyroid gland is a gland in your neck and is part of the endocrine system, a series of glands that produce hormones to regulate metabolism, growth and development, tissue function, sexual function, reproduction, sleep, and mood and other functions.

The thyroid produces two hormones which are secreted into the blood: thyroxine (T4) and triiodothyronine (T3). These hormones are necessary for all the cells in your body to operate normally. The T4, or rather the T3 derived from it, and the T3 secreted directly by the thyroid gland influence the metabolism of your cells. In other words, it regulates the speed with which your body cells work.

Thyroid cancer is one of the few cancers to have increased recently

Thyroid cancer is a cancerous tumor or growth located within the thyroid gland and is the most common of the endocrine cancers. Thyroid cancer is unusual, due to it being one of the few cancers that has seen an increased incidence rate in recent years. This cancer also occurs in all age groups from children through to seniors, though as with the majority of cancers, aging is the primary risk factor.

According estimates from the American Cancer Society there will be about 56,870 new cases of thyroid cancer in the United States in 2017 and of these new cases, around 42,470 will occur in women and about 14,400 will occur in men. They estimate that around 2,010 people (1,090 women and 920 men) will die of thyroid cancer in 2017.

There are three main types of thyroid cancers: differentiated thyroid cancer (DTC – which includes FTC and PTC), poorly differentiated thyroid carcinoma (PDTC) and anaplastic (undifferentiated) thyroid carcinoma (ATC). ATC and PDTC cancers are typically rare, however, they are aggressive and are the least likely to respond to treatment with chemotherapy or radiotherapy.

Honokiol is shown to have anticancer properties

Today we are going to look at an interesting study from December 2016 where honokiol was investigated for the potential treatment of thyroid cancer (1). A team of researchers from Taiwan investigated the possibility that honokiol might be useful in treating thyroid cancers given its potential in other types of cancer as shown in a variety of other studies.

Previous studies have shown that honokiol has anticancer properties against other forms of cancers, such as, skin cancer (2-3), lung cancer (4-5), breast cancer (6-7), ovarian cancer (8-10), prostate cancer (11) and a variety of other cancers (12).

In-vitro tests on multiple human cancer cell lines

The researchers began by in-vitro testing using ARO, WRQ and SW579 human cancer cell lines. The cells were incubated with honokiol and the researchers observed that there was a distinct reduction of cell viability in ARO, WRQ and SW579 cells, this suggests that honokiol did indeed have the potential to treat human thyroid cancers.

Fig 1. Honokiol suppressed the growth of human thyroid cancer cells. Human thyroid cancer cells, (A) ARO, (B) WRO and (C) SW579 cells were treated with honokiol for various dosages and the cellular viabilities were determined after 24, 48 and 72 h post-treatment by CCK-8 analysis. Cells treated with DMSO were used as a negative control, and all of the groups were normalization with the control group. The results are expressed as mean ± SD (n = 9) of three independent experiments.

The researchers then investigated honokiol and its effect on cycle cell arrest in the same three human thyroid cancer cell lines. The control of cell cycle progression is considered an effective approach for controlling the growth of cancer and thus treating it so naturally the researchers wished to see how effective honokiol might be in this regard. Testing showed a significant increase in cell cycle arrest in both ARO and WRO cell lines but only a small increase in the SW579 line, although they do note that the SW579 cells did have an increased vulnerability to apoptosis (cell death). This increase the researchers suggest was due to honokiol inducing caspase-dependent apoptosis and autophagy via the inhibition of PI3 K/Akt (an intracellular signaling pathway important in regulating the cell cycle) and Mitogen-activated protein kinases (MAPK) pathways.

Taken together these in-vitro results suggest that honokiol has potent anticancer properties against human ATC, DTC and PDTC cell types, but there are some differences in the mechanisms of the anticancer activity between the types.

In-vivo tests on ATC thyroid cancer cell line

Next the researchers moved to in-vivo testing, using female xenograft mouse models divided into three randomized groups: A DMSO group (a control substance), 5 mg/kg honokiol group and 15 mg/kg honokiol group. The team decided to test the more aggressive and harder to treat ATC thyroid cancer cells (ARO cell line). All three mouse groups were injected with the ARO cells lines on day 0. After 10 days with the tumor size under 1mm3, the mice were given DMSO or honokiol respectively, every 3 days for 3 weeks. After this 3 week period was over the tumor sizes in the control and treatment groups were compared.

The results were astonishing, the control group average tumor weight was 700 mg, the 5 mg/kg honokiol group 400 mg and the 15 mg/kg was only 200 mg. This makes the 15 mg test group an amazing 72% less weight than the control group!

This confirms the initial in-vitro results in culture, showing that honokiol has a dose-dependent anti-proliferative action also translate to the in-vivo environment.

Conclusion

Taken together these results suggest that honokiol is a promising anticancer therapy with the ability to reduce cancer growth and increase cancer cell cycle arrest. Given the numerous studies showing anticancer, anti-inflammatory, antifibrotic and other the health benefits of honokiol, it is worth considering this supplement as part of your personal supplement plan.

 

References 

(1)Lu, C. H., Chen, S. H., Chang, Y. S., Liu, Y. W., Wu, J. Y., Lim, Y. P., … & Lee, Y. R. (2017). Honokiol, a potential therapeutic agent, induces cell cycle arrest and program cell death in vitro and in vivo in human thyroid cancer cells. Pharmacological Research, 115, 288-298.
(2)Chilampalli, S., Zhang, X., Fahmy, H., Kaushik, R. S., Zeman, D., Hildreth, M. B., & Dwivedi, C. (2010). Chemopreventive effects of honokiol on UVB-induced skin cancer development. Anticancer research, 30(3), 777-783.
(3)Mannal, P. W., Schneider, J., Tangada, A., McDonald, D., & McFadden, D. W. (2011). Honokiol produces anti‐neoplastic effects on melanoma cells in vitro. Journal of surgical oncology, 104(3), 260-264.
(4)Hu, J., Chen, L. J., Liu, L., Chen, X., Chen, P., Yang, G. L., … & Zhao, X. (2008). Liposomal honokiol, a potent anti-angiogenesis agent, in combination with radiotherapy produces a synergistic antitumor efficacy without increasing toxicity. Experimental & molecular medicine, 40(6), 617-628.
(5)Jiang, Q. Q., Fan, L. Y., Yang, G. L., Guo, W. H., Hou, W. L., Chen, L. J., & Wei, Y. Q. (2008). Improved therapeutic effectiveness by combining liposomal honokiol with cisplatin in lung cancer model. BMC cancer, 8(1), 242.
(6)Hou, W., Chen, L., Yang, G., Zhou, H., Jiang, Q., Zhong, Z., … & Tang, M. (2008). Synergistic antitumor effects of liposomal honokiol combined with adriamycin in breast cancer models. Phytotherapy Research, 22(8), 1125-1132.
(7)Wolf, I., O’Kelly, J., Wakimoto, N., Nguyen, A., Amblard, F., Karlan, B. Y., … & Koeffler, H. P. (2007). Honokiol, a natural biphenyl, inhibits in vitro and in vivo growth of breast cancer through induction of apoptosis and cell cycle arrest. International journal of oncology, 30(6), 1529-1538.
(8)Li, Z., Liu, Y., Zhao, X., Pan, X., Yin, R., Huang, C., … & Wei, Y. (2008). Honokiol, a natural therapeutic candidate, induces apoptosis and inhibits angiogenesis of ovarian tumor cells. European Journal of Obstetrics & Gynecology and Reproductive Biology, 140(1), 95-102.
(9)Luo, H., Zhong, Q., Chen, L. J., Qi, X. R., Fu, A. F., Yang, H. S., … & Zhao, X. (2008). Liposomal honokiol, a promising agent for treatment of cisplatin-resistant human ovarian cancer. Journal of cancer research and clinical oncology, 134(9), 937-945.
(10)Liu, Y., Chen, L., He, X., Fan, L., Yang, G., Chen, X., … & Mao, Y. (2008). Enhancement of therapeutic effectiveness by combining liposomal honokiol with cisplatin in ovarian carcinoma. International Journal of Gynecological Cancer, 18(4), 652-659.
(11)Hahm, E. R., Arlotti, J. A., Marynowski, S. W., & Singh, S. V. (2008). Honokiol, a constituent of oriental medicinal herb magnolia officinalis, inhibits growth of PC-3 xenografts in vivo in association with apoptosis induction. Clinical Cancer Research, 14(4), 1248-1257.
(12)Crane, C., Panner, A., Pieper, R. O., Arbiser, J., & Parsa, A. T. (2009). Honokiol mediated inhibition of PI3K/mTOR pathway: A potential strategy to overcome immunoresistance in glioma, breast and prostate carcinoma without impacting T cell function. Journal of immunotherapy (Hagerstown, Md.: 1997), 32(6), 585.