Advanced Prostate Cancer
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Foods/Supplements-Vitamins: Magnolia - magnolol - honokiol - obovatol - Relora

Timing of this post is due to Gus, who recently posted enthusiastically about honokiol & time to Lupron failure.

[1] The following deals with three constituents of the magnolia that have been shown to have anti-tumor effects in PCa: magnolol, honokiol & obovatol.

Mention should be made of Relora:

"Relora® is a proprietary blend of Magnolia officinalis bark extract and Phellodendron amurense bark extract. Relora® is supported by three peer-reviewed, randomized, double-blind, placebo-controlled publications that demonstrate Relora®'s positive effects on mood state scores and weight maintenance in stress eaters." [1a]

A wide range of brands repackage Relora - sometimes with added ingredients. It seems to be popular. I admire the audacity of the marketers. Relora is proven to reduce overnight levels of the stress hormone cortisol. Therefore, it keeps stress eaters out of the kitchen - & they lose weight.

There was a time when I badly needed to tackle the bad thoughts one has, due to PCa, at 3 a.m. This is a time when cortisol is naturally on the rise. Relora before bed neatly lowers 3 a.m. cortisol without druggy side effects. (Raiding the fridge was not my response to stress, so I did not lose weight.)

No mention as to the breakdown of the "proprietary ... Magnolia officinalis bark extract". Surely there must be some Magnolol & Honokiol in there?

A cheap Honokiol product from Swanson [1b] claims:

"Standardized to minimum 90% honokiol"

The high-end NutriCology brand they sell [1c] states "Honokiol + Magnolol 90%". Do the two isomers have synergy?

The very expensive ecoNugenics brand at Vitacost promises 98% Honokiol [1d].

No luck at iHerb.

I seem to recall that there was some hype associated with honokiol a dozen years ago, & that interest quickly waned. I suppose that most men were looking for a quick drop in PSA as monotherapy. Perhaps it has more value as part of a therapy. Certainly, the observation by Gus can't be ignored.

[2] Magnolol.

"Magnolol is an organic compound that is classified as lignan. It is a bioactive compound found in the bark of the Houpu magnolia (Magnolia officinalis) or in M. grandiflora. The compound exists at the level of a few percent in the bark of species of magnolia, the extracts of which have been used in traditional Chinese and Japanese medicine."

[2a] (2009 - U.S.)

"We observed that treatment of prostate cancer cells for 24 h with magnolol, a phenolic component extracted from the root and stem bark of the oriental herb Magnolia officinalis, induced apoptotic cell death in a dose- and time-dependent manner."

"Interestingly, at similar concentrations (60 microM), magnolol treatment did not affect the viability of normal human prostate epithelial cell (PrEC) line."

[2b] (2010 - Korea)

"Magnolol, a hydroxylated biphenyl compound isolated from the root and stem bark of Magnolia officinalis, has been reported to have anticancer activity, but little is known about its molecular mechanisms of action. Increased expression of cyclooxygenase-2 (COX-2), a key enzyme in arachidonic acid metabolism, has been identified in many cancer types. Matrix metalloproteinases (MMPs) are enzymes involved in various steps of metastasis development. The objective of this study was to study the effects of magnolol on cancer invasion and metastasis using PC-3 human prostate carcinoma cells. Cellular proliferation was determined by MTT colorimetric assay. Magnolol inhibited cell growth in a dose-dependent manner. In an invasion assay conducted in Transwell chambers, magnolol showed 33 and 98% inhibition of cancer cell at 10 microM and 20 microM concentrations, respectively, compared to the control. The expression of MMP-2/-9 and COX-1/-2 was assessed ... The protein and mRNA levels of both MMP-2 and MMP-9 were down-regulated by magnolol treatment in a dose-dependent manner. These results demonstrate the antimetastatic properties of magnolol in inhibiting the adhesion, invasion, and migration of PC-3 human prostate cancer cells."

[2c] (2014 - Canada)

"This study investigated the effects of magnolol, a compound found in the roots and bark of the magnolia tree Magnolia officinalis, on the behavior of 2 androgen insensitive human prostate cancer cell lines, DU145 and PC3, in vitro. Magnolol, in a 24-h exposure at 40 and 80 μM, was found to be cytotoxic to cells. Magnolol also affected cell cycle progression of DU145 and PC3 cells, resulting in alterations to the cell cycle and subsequently decreasing the proportion of cells entering the G2/M-phase of the cell cycle."

"This study has demonstrated that magnolol can alter the behavior of androgen insensitive human prostate cancer cells in vitro ..."

[2d] (2014 - Canada)

"Magnolol, (80 μM, 6 hour exposure) was found to affect the expression of insulin-like growth factor-1 (IGF-1) and associated proteins. In both cell lines, protein expression of IGF-1 and insulin-like growth factor binding protein-5 (IGFBP-5) were significantly decreased, while protein expression of IGFBP-3 was significantly increased. Additionally, protein expression of insulin-like growth factor-1 receptor (IGF-1R) was significantly increased ... in PC3 cells, while IGFBP-4 protein expression was significantly increased in LNCaP cells."

[3] Honokiol

"Honokiol is a plant lignan isolated from the bark and seed cones of the magnolia tree"

"honokiol ... is an isomer of magnolol"

"Honokiol has been extracted from a number of species of Magnolia native to many regions of the globe. Magnolia grandiflora, which is native to the American South, as well as Mexican species like Magnolia dealbata have been found to be sources of honokiol. Traditionally in Asian medicine, the Magnolia biondii, Magnolia obovata, and Magnolia officinalis are commonly used."

[3a] (2007 - U.S.)

Odd perhaps that this earliest Honokiol-PCa study should have looked at the effect of it & docetaxel in the bones of mice "inoculated in vivo with androgen-independent PCa, C4-2 cells ..."

"Honokiol induced apoptosis in all cell lines tested. In PCa cells honokiol induced apoptosis via the activation of caspases 3, 8, and 9 and the cleavage of poly-adenosine diphosphate ribose polymerase in a dose- and time-dependent manner. Honokiol was shown to inhibit the growth and depress serum PSA in mice harboring C4-2 xenografts in the skeleton and the combination with docetaxel showed additive effects that inhibited further growth without evidence of systemic toxicity. Immunohistochemical staining confirmed honokiol exhibited growth-inhibitory, apoptotic, and antiangiogenic effects on PCa xenografts."

[3b] (2007 - U.S.)

"The present study was undertaken to gain insights into the mechanism of cell cycle arrest caused by honokiol, a constituent of oriental herb Magnolia officinalis. The honokiol treatment decreased the viability of PC-3 and LNCaP human prostate cancer cells in a concentration- and time-dependent manner, which correlated with G0-G1 phase cell cycle arrest."

"The honokiol treatment caused the generation of reactive oxygen species (ROS), and the cell cycle arrest caused by honokiol was partially but significantly attenuated in the presence of antioxidant N-acetylcysteine."

(Another reminder to stay away from NAC when using polyphenols.)

[3c] (2008 - U.S.)

"Exposure of human prostate cancer cells (PC-3, LNCaP, and C4-2) to honokiol resulted in apoptotic DNA fragmentation in a concentration- and time-dependent manner irrespective of their androgen responsiveness or p53 status."

"Oral gavage of 2 mg honokiol/mouse (thrice a week) significantly retarded growth of PC-3 xenografts without causing weight loss. Tumors from honokiol-treated mice exhibited markedly higher count of apoptotic bodies and reduced proliferation index and neovascularization compared with control tumors."

[3d] (2009 - U.S.)

"Honokiol mediated inhibition of PI3K/mTOR pathway: A potential strategy to overcome immunoresistance in ... prostate carcinoma without impacting T cell function"

"Inhibition of the ... (PI3K)/... (mTOR) pathway is an appealing method for decreasing the immunoresistance and augmenting T cell-mediated immunotherapy. A major impediment to this strategy is the impact of conventional PI3K/mTOR pathway inhibitors on T cell function. In particular, rapamycin, is a well-known immunosuppressant that can decrease the activity of the PI3K/mTOR pathway in tumor cells, but also has a profound inhibitory effect on T cells. Here we show that Honokiol, a natural dietary product isolated from an extract of seed cones from Magnolia grandiflora, can decrease PI3K/mTOR pathway-mediated immunoresistance of glioma, breast and prostate cancer cell lines, without affecting critical proinflammatory T cell functions."

[3e] (2014 -U.S.)

"We have shown previously that honokiol (HNK), a bioactive component of the medicinal plant Magnolia officinalis, inhibits growth of human prostate cancer cells in vitro and in vivo. However, the effect of HNK on androgen receptor (AR) signaling has not been studied."

"Nuclear translocation of AR stimulated by a synthetic androgen (R1881) was markedly suppressed in the presence of HNK. Downregulation of AR protein resulting from HNK exposure was attributable to transcriptional repression as well as proteasomal degradation. HNK-mediated suppression of AR protein was maintained in LNCaP cells after knockdown of p53 protein. "

[3f] (2014 - U.S.)

"... the present study demonstrates, for the first time, that HNK induces ROS-mediated cytoprotective autophagy in prostate cancer cells."

[3g] (2016 - U.S.)

"The present study indicates that c-Myc, which is often overexpressed in early and late stages of human prostate cancer, is a novel target of prostate cancer growth inhibition by HNK."

[4] Obovatol

"Obovatol is a biphenolic anti-inflammatory, anxiolytic, and nootropic isolated from the bark of Magnolia obovata." (which is also a source of magnolol and honokiol)

[4a] (2008 - S. Korea)

"Treatment of obovatol (10, 15, 20, 25 microM) inhibits {prostate} cancer cell {LNCaP and PC-3} growth in the absence or the presence of tumor necrosis factor-alpha (TNF-alpha , 10 ng/ml) and tetradecanoyl phorbol acetate (TPA 10 or 50 nM) in a concentration-dependent manner through induction of apoptotic cell death."

"Cytotoxic activity was not observed in normal cells with up to 50 muM obovatol."

[4b] (2008 - S. Korea)

"Nuclear transcription factor-kappaB (NF-kappaB) is constitutively activated in prostate ... cancer and is related with the resistance of cancer cells against chemotherapeutics. Previously, we found that obovatol, an active compound isolated from Magnolia obovata, inhibited cancer cell growth through inhibition of NF-kappaB activity. We investigated here whether obovatol could sensitize cancer cells against docetaxel through inhibition of NF-kappaB activity in prostate cancer (LNCaP and PC-3) ... cells."

"The combination treatment with each drug at one half the respective IC(50) dose (5 microM obovatol + 5 nM docetaxel) was more effective and significant (60%-70%) in the inhibition of cancer cell growth than single treatment by each drug (20%-40%); inhibition was exerted through a significant increase of apoptosis induction (60%-80%) by the combination treatment compared to the single treatment (10%-30%)."

"Similar combination effects of obovatol with other chemotherapeutic agents (paclitaxel, cisplatin, and doxorubicin) on the inhibition of cell growth and NF-kappaB activity were also found. These results indicate that obovatol augments cell growth inhibition by chemotherapeutics through inactivation of NF-kappaB and suggest that obovatol may have therapeutic advantages in the combination treatment with other chemotherapeutics."














[3c] clincancerres.aacrjournals....








3 Replies

I can't help but read this and wonder what, if anything, is happening with clinical trials of these substances. A number of the studies quoted were done 8 or 9 years ago. All reports seem to believe the toxicity of the substances are very low or zero. The in vitro results seem promising and yet as far as I know, there seems to be very little follow through with drug development. What am I missing....? Is there more going on than I am aware of or a concern about being able to patent natural ingredients? It's frustrating when you have been diagnosed with advanced, incurable PCa.


I am grateful for any study of the more obscure botanicals.

Funding in the U.S. for studies mostly come from BigPharma, of course, so I was surprised by the number of U.S. studies for honokiol. The souce of the funds:

National Institute for Health/National Cancer Institute

Interestingly, here is the (3d) "Financial Disclosure: JA has filed for international patent rights for Honokiol. Emory University has filed for US rights." That's very cheeky!

But it does show confidence in the product.




Thanks for the research on Honokiol. Another property of Honokiol is unlike many supplements (curcumin), honokiol is very bioavailable even being able to cross the blood brain barrier which is highly unusual for a supplement.



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