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Honokiol Extract and Integrative Cancer Treatment

Honokiol Extract and Integrative Cancer Treatment

2016 - 08 - 17 | Author: Susan Silberstein PhD

magnolia honokiolMedicinal plants are known to be the source of many common pharmaceuticals. Drugs derived from the plant kingdom include aspirin from white willow, digitalis from foxglove, morphine from poppy, and chemotherapy agents like vincristine from periwinkle and taxol from the yew. Many herbs and plants also play a supportive role in conjunction with conventional cancer therapy. One such natural compound is honokiol, extracted from the magnolia tree. Traditionally used in Japanese and Chinese herbal medicines, honokiol has been found to be a powerful, versatile tool in integrative cancer treatment.

A highly active compound derived from magnolia bark, honokiol has been used in Traditional Chinese Medicine (TCM) for treating digestive disorders, anxiety and other chronic conditions. Over the last decade or so, honokiol has been the subject of extensive research as an adjuvant cancer treatment, demonstrating remarkable benefits through diverse mechanisms of action. The compound shows promise for a number of solid tumors and hematological cancers and appears to be particularly effective in reversing multi-drug resistance and synergizing with other treatments.

Mechanisms of Action

A growing body of data demonstrates honokiol’s multiple mechanisms of action against cancer. Honokiol appears to be particularly active in regulating cell cycle arrest and promoting apoptosis (programmed cancer cell death) by inhibiting a number of cancer signaling pathways.

A July 14, 2008 article in Science Daily reported on research from Emory University in Atlanta showing that this natural magnolia compound interferes with a critical pathway for cancer growth that was previously considered "undruggable." Specifically, it blocks survival signals from a difficult-to-target family of genes in breast, lung and bladder cancer cells.1

A comprehensive 2011 review highlights the multiple pathways by which honokiol influences apoptosis and inhibits multiple cancer cell types including breast, prostate, colon, liver, lung and others.2 In non-small cell lung cancer, honokiol inhibited cancer growth and induced apoptosis.3 In leukemia, honokiol promoted cell cycle arrest and apoptosis by blocking cancer survival signals.4 A 2012 study showed honokiol halted growth and metastasis of melanoma.5 Another study demonstrated that honokiol-induced cell cycle arrest irrespective of the hormone sensitivity of prostate cancer cells.6

Honokiol can also inhibit tumor angiogenesis by modulating various signaling pathways that promote cancer cell growth. Honokiol has been shown to inhibit the spread of cancer cells through the lymph system by inhibiting one of the primary pathways involved in growth stimulation related to VEGF (vascular endothelial growth factor).7 A 2012 study showed that honokiol inhibited angiogenic pathways to slow the spread of gastric cancer.8

Another 2012 study showed honokiol’s direct cytotoxic activity, showing the compound attacked metastatic bone cancer cells directly.9 Honokiol is highly bioavailable and its small molecular size allows it to reach target tissues and cross the blood-brain and blood-cerebrospinal fluid barriers, making it an excellent adjunct for brain tumors like gliomas and neuroblastomas.10, 11

Synergistic with Cancer Treatments

One of honokiol’s most important attributes is its ability to act synergistically with conventional cancer treatments. Numerous studies show the remarkable ability of honokiol to enhance the effectiveness of radiation and certain chemotherapy drugs in a number of cancers, including the following studies conducted between 2005 and 2013 which demonstrated that honokiol:

  • Synergized with chemotherapy drugs in multidrug resistant breast cancer12
  • Sensitized treatment-resistant colon cancer cells to radiation therapy13
  • Enhanced the action of cisplatin against colon cancer14
  • Re-sensitized cancer cells to doxorubicin in multidrug resistant uterine cancer15
  • Performed synergistically with the drug imatinib against human leukemia cells16
  • Sensitized cancer cells to radiation treatments17
  • Potentiated the activity of cisplatin in animal models of ovarian cancer18
  • Enhanced the cytotoxicity of drugs used for B-cell chronic lymphocytic leukemia19

Anti-inflammatory and Antioxidant Protection

In addition to its direct anticancer actions, honokiol is also shown to offer other valuable anti-inflammatory and anti-oxidative effects that relate to its mechanisms against cancer. Honokiol offers powerful free radical scavenging benefits against reactive oxygen species.20,21 Its inhibition of reactive oxygen was actually shown to be 1,000 times that of α-tocopherol (vitamin E).22 (Interestingly, honokiol is also a selective pro-oxidant, generating reactive oxygen against certain cancer cells. The ability of honokiol to function either as an antioxidant or a pro-oxidant depending on the need is one of its most remarkable features.) A 2005 study suggested honokiol can protect the brain against amyloid plaque neurotoxicity in the formation of Alzheimer’s disease23 by reducing inflammation and oxidation in the brain.

Source and Dosages

The most concentrated and purest source of honokiol is HonoPure by EcoNugenics, offering 98% pure honokiol extract for multiple indications. The company has agreed to offerBeatCancer.org clients a 15% discount on honokiol, as well as their entire line of products for prostate health, breast health, immune support, hormonal support, and heavy metal detoxification, among others. Just enter the coupon code BCO15 when you place your order. (For orders of $200 or more, use the code BCO20 and get 20% off).

Below are suggested dosages according to clinical use guidelines:

  • Active cancer: 1 g x 3/day (starting at lower dosage and building up to full dose)
  • Cancer prevention/post cancer therapy: 1 g/day
  • Inflammatory conditions: 250-500mg x 2/day
  • Anxiety: 250 mg x 2/day

Honokiol’s in vivo toxicity record thus far shows it to be extremely safe.

Conclusion

The research on this remarkable compound continues to show beneficial effects for numerous serious and difficult-to-treat conditions, including protection against neurological conditions like Alzheimer’s disease23 and stroke damage,24 viral and bacterial infections like hepatitis C, 25-26 and multiple drug resistant cancer. It is currently used clinically by a growing number of integrative and naturopathic physicians.

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References:

[1] Magnolia compound hits elusive target in cancer cells. Science Daily July 14, 2008. https://www.sciencedaily.com/releases/2008/07/080711214125.htm
[2] Xu HL, Tang W, Du GH, Kokudo N. Targeting apoptosis pathways in cancer with magnolol and honokiol, bioactive constituents of the bark of Magnolia officinalis. Drug Discov Ther. 2011 Oct;5(5):202-10.
[3] Singh T, Prasad R, Katiyar SK. Inhibition of class 1 histone deacetylases in non-small cell lung cancer by honokiol leads to suppression of cancer cell growth and induction of cell death in vitro and in vivo. Epigenetics. 2013 Jan1;8(1):54-65.
[4] Ishikawa C, Arbiser JL, Mori N. Honokiol induces cell cycle arrest and apoptosis via inhibition of survival signals in adult T-cell leukemia. Biochim Biophys Acta. 2012 Jul;1820(7):879-87.
[5] Kaushik G, Ramalingam S, Subramanium D, Rangarajan P, Protti P, Rammamoorthy P, Anant S, Mammen JM. Honokiol induces cytotoxic and cytostatic effects in malignant melanoma cancer cells. Am J Surg. 2012 Dec;204(6):868-73.
[6] Hahm ER, Singh SV. Honokiol causes G0-G1 phase cell cycle arrest in human prostate cancer cells in association with suppression of retinoblastoma protein level/phosphorylation and inhibition of E2F1 transcriptional activity. Mol Cancer Ther. 2007 Oct;6(10):2686-95.
[7] Wen J, Fu AF, Chen LJ, Xie XJ, Yang GL, Chen XC, Wang YS, Li J, Chen P, Tang MH, Shao XM, Lu Y, Zhao X, Wei YQ. Liposomal honokiol inhibits VEGF-D-induced lymphangiogenesis and metastasis in xenograft tumor model. Int J Cancer. 2009 Jun 1;124(11):2709-18.
[8] Liu SH, Wang KB, Lan KH, Lee WJ, Pan HC, Wu SM, Peng YC, Chen YC, Shen CC, Cheng HC, Liao KK, Sheu ML. Calpain/SHP-1 interaction by honokiol dampening peritoneal dissemination of gastric cancer in nu/nu mice. PLoS One. 2012;7(8):e43711.
[9] Steinmann P, Walters DK, Arlt MJ, Banke IJ, Ziegler U, Langsam B, Arbiser J, Muff R, Born W, Fuchs B. Antimetastatic activity of honokiol in osteosarcoma. Cancer. 2012 Apr 15;118(8): 2117-27.
[10] Lin JW, Chen JT, Hong CY, et al. Honokiol traverses the blood-brain barrier and induces apoptosis of neuroblastoma cells via an intrinsic bax-mitochondrion-cytochrome c-caspase protease pathway. Neuro Oncol. 2012 Mar;14(3):302-14.
[11] Wang X, Duan X, Yang G, et al. Honokiol crosses BBB and BCSFB, and inhibits brain tumor growth in rat 9L intracerebral gliosarcoma model and human U251 xenograft glioma model. PLoS One. 2011 Apr 29;6(4):e18490. doi: 10.1371/journal.pone.0018490.
[12] Tian W, Deng Y, Li L, He H, Sun J, Xu D. Honokiol synergizes chemotherapy drugs in multidrug resistant breast cancer cells via enhanced apoptosis and additional programmed necrotic death. Int J Oncol. 2013 Feb;42(2):721-32.
[13] He Z, Subramaniam D, Ramalingam S, Dhar A, Postier RG, Umar S, Zhang Y, Anant S.Honokiol radiosensitizes colorectal cancer cells: enhanced activity in cells with mismatch repair defects. Am J Physiol Gastrointest Liver Physiol. 2011 Nov;301(5):G929-37.
[14] Cheng N, Xia T, Han Y, He QJ, Zhao R, Ma JR. Synergistic antitumor effects of liposomal honokiol combined with cisplatin in colon cancer models. Oncol Lett. 2011 Sep 1;2(5):957-962.
[15] Angelini A, Di Ilio C, Castellani ML, Conti P, Cuccurullo F. Modulation of multidrug resistance p-glycoprotein activity by flavonoids and honokiol in human doxorubicin-resistant sarcoma cells (MES-SA/DX-5): implications for natural sedatives as chemosensitizing agents in cancer therapy. J Biol Regul Homeost Agents. 2010 Apr-Jun;24(2):197-205.
[16] Wang Y, Yang Z, Zhao Z. Honokiol induces parapoptosis and apoptosis and exhibits schedule-dependent synergy in combination with imatinib in human leukemia cells. Toxicol Mech Methods. 2010 Jun;20(5):234-41.
[17] Ponnurangam S, Mammen JM, Ramalingam S, He Z, Zhang Y, Umar S, Subramaniam D, Anant S. Honokiol in combination with radiation targets notch signaling to inhibit colon cancer stem cells. Mol Cancer Ther. 2012 Apr;11(4):963-72.
[18] Liu Y, Chen L, He X, Fan L, Yang G, Chen X, Lin X, DU L, Li Z, Ye H, Mao Y, Zhao X, Wei Y. Enhancement of therapeutic effectiveness by combining liposomal honokiol with cisplatin in ovarian carcinoma. Int J Gynecol Cancer. 2008 Jul-Aug;18(4):652-9.
[19] Battle TE, Arbiser J, Frank DA. The natural product honokiol induces caspase-dependent apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells. Blood. 2005 Jul 15;106(2):690-7.
[20] Liou KT, Shen YC, Chen CF, Tsao CM, Tsai SK. The anti-inflammatory effect of honokiol on neutrophils: mechanisms in the inhibition of reactive oxygen species production. Eur J Pharmacol. 2003 Aug 15;475(1-3):19-27.
[21] Zhao C, Liu ZQ. Comparison of antioxidant abilities of magnolol and honokiol to scavenge radicals and to protect DNA. Biochimie. 2011 Oct;93(10):1755-60. Epub 2011 Jun 23.
[22] Tsai SK, Huang SS, Hong CY. Myocardial protective effect of honokiol: an active component in Magnolia officinalis. Planta Med. 1996 Dec;62(6):503-6.
[23] Liu B, Hattori N, Zhang NY, Wu B, Yang L, Kitagawa K, Xiong ZM, Irie T, Inagaki C. Anxiolytic agent, dihydrohonokiol-B, recovers amyloid beta protein-induced neurotoxicity in cultured rat hippocampal neurons. Neurosci Lett. 2005 Aug 12-19;384(1-2):44-7.
[24] Chen C M, Liu S H, Lin-Shiau SY. Honokiol, a neuroprotectant against mouse cerebral ischemia, mediated by preserving Na+, K+-ATPase activity and mitochondrial functions. Basic Clin Pharmacol Toxicol. 2007 Aug;101(2);108-16.
[25] Park J, Lee J, Jung E, Park Y, Kim K, Park B, Jung K, Park E, Kim J, Park D. In vitro antibacterial and anti-inflammatory effects of honokiol and magnolol against Propionibacterium sp. Eur J Pharmacol. 2004 Aug 2;496(1-3):189-95.
[26] Lan KH, Wang YW, Lee WP, Lan KL, Tseng SH, Hung LR, Yen SH, Lin HC, Lee SD. Multiple effects of Ho nokiol on the life cycle of hepatitis C virus. Liver Int. 2012 Jul;32(6):989-97.

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