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Alert Number 92

Honokiol: Miracle Herb or Feel Happy Pill?

Date: May 8, 2005

The latest edition of Blood has two articles from Dana Farber on a natural compound called Honokiol.

Honokiol is obtained from the bark of the magnolia tree, I believe it is a member of a family of compounds called lignans. It has received press among alternate medicine folks. Typing "honokiol" into PubMed search engine gets close to a hundred hits. It has interesting chemistry: NF-kB inhibition, anti-angiogenesis, p53 independent cytotoxicity, caspace activation, high therapeutic index, synergy with chemotherapy drugs, etc., etc. But this is the first time I have seen it addressed by researchers of this caliber, or specifically referring to CLL.

There is some muted concern that honokiol may have physical dependence issues, as well as barbiturate type psychological effects. It has been compared to valium, and indeed there are indications that it has similar anxiety suppressing effects. One paper also said it is the herbal equivalent of Viagra! (Let's see: it kills CLL cells, makes you happy, and it lets you give "Enzyte Bob" a run for his money? Wow. Now if only it cured male pattern baldness as well …)

I am trying to check this out, see if there are serious toxicity issues associated with CLL patients taking this herbal product over long periods of time. So, pretty please, will you hold off rushing to the health food store and getting yourself into a happy state by swallowing a fistful of this herbal product? As a first pass I looked it up on a reputable supplement watch site (link below), and it looks pretty good thus far. But the devil is in the details, so hold your horses for just a little while, I promise I will get back to you on this ASAP.

Link: Entry for Honokiol on Supplementwatch.

Be well, stay smart.

Chaya
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Abstract

Blood. 2005 Mar 31

The natural product Honokiol induces caspase-dependent apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells.

Battle TE, Arbiser J, Frank DA.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; Departments of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

B-CLL remains an incurable disease that requires innovative new approaches to improve therapeutic outcome. Honokiol is a natural product known to possess potent anti-neoplastic and anti-angiogenic properties. We examined whether honokiol can overcome apoptotic resistance in primary tumor cells derived from B-CLL patients. Honokiol induced caspase-dependent cell death in all of the B-CLL cells examined and was more toxic toward B-CLL cells than to normal mononuclear cells, suggesting greater susceptibility of the malignant cells. Honokiol-induced apoptosis was characterized by the activation of caspases 3, 8, and 9 and cleavage of PARP. Exposure of B-CLL cells to honokiol resulted in up-regulation of bax and down-regulation of the expression of the key survival protein Mcl-1, which is associated with response to treatment in B-CLL patients. In addition, B-CLL cells pre-treated with IL-4, a cytokine known to support B-CLL survival, underwent apoptosis when subsequently incubated with honokiol, indicating that honokiol could also overcome the pro-survival effects of IL-4. Furthermore, honokiol enhanced cytotoxicity induced by fludarabine, cladribine, or chlorambucil. These data indicate that honokiol is a potent inducer of apoptosis in B-CLL cells and should be examined for further clinical application either as a single agent or in combination with other anticancer agents.

PMID: 15802533
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Blood. 2005 May 3;

Honokiol overcomes conventional drug resistance in human multiple myeloma by induction of caspase-dependent and independent apoptosis.

Ishitsuka K, Hideshima T, Hamasaki M, Raje N, Kumar S, Hideshima H, Shiraishi N, Yasui H, Roccaro AM, Richardson P, Podar K, Le Gouill S, Chauhan D, Tamura K, Arbiser J, Anderson KC.

Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.

Honokiol (HNK) is an active component purified from Magnolia, a plant used in traditional Chinese and Japanese medicine. Here we show that HNK significantly induces cytotoxicity in human multiple myeloma (MM) cell lines and tumor cells from patients with relapsed refractory MM. Neither co-culture with bone marrow stromal cells nor cytokines (interleukin-6 and insulin-like growth factor-1) protect against HNK-induced cytotoxicity. Although, activation of caspases 3, 7, 8 and 9 is triggered by HNK, the pan-caspase inhibitor z-VAD-fmk does not abrogate HNK-induced apoptosis. Importantly, release of an executioner of caspase-independent apoptosis, apoptosis-inducing factor (AIF) from mitochondria is induced by HNK treatment. HNK induces apoptosis in SU-DHL4 cell line, which has low levels of caspase-3 and -8 associated with resistance to both conventional and novel drugs. These results suggest that HNK induces apoptosis via both caspase-dependent and -independent pathways. Furthermore, HNK enhances MM cell cytotoxicity and apoptosis induced by bortezomib. In addition to its direct cytotoxicity to MM cells, HNK also represses tube formation by endothelial cells, suggesting that HNK inhibits neovascurization in the bone marrow microenvironment. Taken together, our results provide the preclinical rationale for clinical protocols of HNK to improve patient outcome in MM.

PMID: 15870175
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