Maspin. (& Curcumin, Luteolin, etc.)

[pjoshea13]

New study below [1].

The Maspin-PCa literature is barely 20 years old, but there have been some intriguing findings.

The name doesn't give much away - Maspin (mammary serine protease inhibitor).

Maspin is considered to be a tumor suppressor gene. In PCa, its presence is associated with improved adhesion to the cellular matrix. Loss of Maspin is associated with motility & metastasis.

Strangely, ADT seems to induce the expression of Maspin.

The new study is titled "Maspin Enhances the Anticancer Activity of Curcumin in Hormone-refractory Prostate Cancer Cells".

"Androgen ablation mediated maspin-induction has been identified in cancer patients."

"Our present study showed that PC-3 cells (with higher maspin expression) were more sensitive than DU145 cells to curcumin treatment (with lower maspin expression)."

"... maspin silencing reduced curcumin sensitivity of PC-3 cells, as evidenced by reduced apoptotic cell death."

"Conclusion: Maspin can enhance the sensitivity of HRPC cells to curcumin treatment."

For 'HRPC' read 'CRPC'.

...

Two things come to mind after reading the above:

(i) perhaps Maspin can be brought back by natural means?

(ii) perhaps Maspin can sensitize PCa to different treatments? e.g. chemo & radiation.

...

[2] (2016 - U.S.) "Maspin Expression in Prostate Tumor Cells Averts Stemness and Stratifies Drug Sensitivity"

[3] (2014 - U.S.)

"Accumulated evidence demonstrates an anti-tumor effect of maspin on tumor growth, invasion and metastasis. The molecular mechanism underlying these biological functions of maspin is thought to be through histone deacetylase inhibition, key to the maintenance of differentiated epithelial phenotype. Since tumor-driven stromal reactivities co-evolve in tumor progression and metastasis, it is not surprising that maspin expression in tumor cells inhibits extracellular matrix degradation, increases fibrosis and blocks hypoxia-induced angiogenesis. Using the athymic nude mouse model capable of supporting the growth and progression of xenogeneic human prostate cancer cells, we further demonstrate that maspin expression in tumor cells elicits neutrophil- and B cells-dependent host tumor immunogenicity. Specifically, mice bearing maspin-expressing tumors exhibited increased systemic and intratumoral neutrophil maturation, activation and antibody-dependent cytotoxicity, and decreased peritumoral lymphangiogenesis. These results reveal a novel biological function of maspin in directing host immunity towards tumor elimination that helps explain the significant reduction of xenograft tumor incidence in vivo and the clinical correlation of maspin with better prognosis of several types of cancer. Taken together, our data raised the possibility for novel maspin-based cancer immunotherapies."

[4] (2012 - U.S.)

"Resveratrol inhibits cancer by reducing cell proliferation and metastasis and by inducing apoptosis. These actions could be explained by its ability to inhibit (ERK-1/2), Akt and suppressing the levels of estrogen and insulin growth factor -1 (IGF-1) receptor. How these processes are manifested into the antitumor actions of resveratrol is not clear. Using microarray studies, we show that resveratrol reduced the expression of various prostate-tumor associated microRNAs (miRs) including miR-21 in androgen-receptor negative and highly aggressive human prostate cancer cells, PC-3M-MM2. This effect of resveratrol was associated with reduced cell viability, migration and invasiveness. Additionally, resveratrol increased the expression of tumor suppressors, PDCD4 and maspin, which are negatively regulated by miR-21."

[5] (2013 - U.S.)

Note: Tumor suppressor genes are often silenced epigenetically - not via mutation. One such mechanism is by preventing the DNA promoter regions from being accessed. DNA is wrapped tightly around histone proteins. Acetylation loosens the strands for access, but tumors produce deacetylase to prevent this. Maspin inhibits histone deacetylase-1 [HDAC1].

"Maspin, a class II tumor suppressor, is often downregulated during tumor progression and its depletion from the nucleus is associated with poor prognosis. Recently, we reported that reintroduction of maspin is sufficient for redifferentiation of prostate cancer cells to epithelial phenotype, a reversal of epithelial-to-mesenchymal transition. We have linked this effect of maspin with its ability to directly inhibit HDAC1, thereby influencing the acetylation state of transcription factors and other proteins."

[6] (2011 - China)

"Luteolin is a polyphenolic flavone and has antitumor activity for many cancers. The prostate-derived Ets factor (PDEF), a novel epithelium-specific Ets transcription factor, acts as an androgen-independent transcriptional activator of the prostate-specific antigen (PSA) promoter."

"luteolin treatments at proapoptosis dosage, enhanced gene expression of PDEF, B-cell translocation gene 2 (BTG2), N-myc downstream regulated gene 1 (NDRG1) and Maspin."

[7] (2010 - U.S.)

"Our data demonstrated that {apple peel extract}, obtained from organic Gala apples, imparted significant reduction in the viability of a variety of cancer cell lines." - including PCa DU145 cells.

"In addition, {apple peel extract} treatment resulted in a marked increase in maspin, a tumor suppressor protein that negatively regulates cell invasion, metastasis, and angiogenesis."

Protective polyphenols are usually concentrated in the outer layers of plants & their fruit. I doubt that normal chewing would release a significant amount of the phytochemicals in apple peel.

In the absence of a true extract, a powdered skin product might be useful. I can't vouch for the following, but it might be useful:

swansonvitamins.com/organic...

My wife just made an apple pie for friends. 3 lbs Granny Smith apples - that's a lot of discarded peel. I should have put it in the blender & swallowed the stuff.

-Patrick

[1] ar.iiarjournals.org/content...

Maspin Enhances the Anticancer Activity of Curcumin in Hormone-refractory Prostate Cancer Cells

WAN-LI CHENG1, CHIEN-YU HUANG2,3, CHENG-JENG TAI4,5, YU-JIA CHANG1,2,6,7⇑ and CHIN-SHENG HUNG1,2,6⇑

+ Author Affiliations

1Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C.

2Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C.

3Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan, R.O.C.

4Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C.

5Division of Hematology and Oncology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan, R.O.C.

6Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan, R.O.C.

7Cancer Research Center, Taipei Medical University Hospital, Taipei, Taiwan, R.O.C.

Correspondence to: Yu-Jia Chang and Chin-Sheng Hung, Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, 250 Wu-Xin Street, Taipei City, 110 Taiwan, R.O.C. Tel/Fax: [phone] ext. 3027, e-mail: [e-mail]

Abstract

Background/Aim: Androgen deprivation therapy remains the principal treatment for patients with advanced prostate cancer, though, most patients will eventually develop hormone-refractory prostate cancer (HRPC). Androgen ablation mediated maspin-induction has been identified in cancer patients. However, the role of maspin on the anticancer activity of curcumin derived from turmeric (Curcuma longa) in HRPC cells has not been elucidated. Materials and Methods: The anticancer action of curcumin in hormone-independent prostate cancer cells (DU145, and PC-3) was determined by measures of cell survival rate. The cause of maspin silencing on the anti-tumor abilities of curcumin in PC-3 cells was evaluated by measures of cell survival rate, cell-cycle distribution, and apoptosis signaling analysis. Results: Our present study showed that PC-3 cells (with higher maspin expression) were more sensitive than DU145 cells to curcumin treatment (with lower maspin expression). RNA interference-mediated maspin silencing reduced curcumin sensitivity of PC-3 cells, as evidenced by reduced apoptotic cell death. After exposure to curcumin, maspin-knockdown cells showed lower expression levels of pro-apoptotic proteins, Bad and Bax, as compared with control cells. Conclusion: Maspin can enhance the sensitivity of HRPC cells to curcumin treatment.

...

[2] ncbi.nlm.nih.gov/pmc/articl...

[3] ncbi.nlm.nih.gov/pmc/articl...

[4] ncbi.nlm.nih.gov/pmc/articl...

[5] ncbi.nlm.nih.gov/pmc/articl...

[6] onlinelibrary.wiley.com/doi...

[7] ncbi.nlm.nih.gov/pubmed/204...

[petercraig2]

Patrick thank you and always for your insight and shared information which is always great.

I take 160 mg Curcumin daily so good to have confirmation of its' benefits.

However added benefit for me and everyone else on Curcumin;

Curcumin improves memory and mood

Twice-daily supplements boosted cognitive power over 18 months

Date:January 23, 2018

Source:University of California - Los Angeles

Summary:Daily consumption of a certain form of curcumin -- the substance that gives Indian curry its bright color -- improved memory and mood in people with mild, age-related memory loss.

Share:Turmeric powder and roots. Turmeric contains curcumin, which has been shown to have anti-inflammatory and antioxidant properties.

Lovers of Indian food, give yourselves a second helping: Daily consumption of a certain form of curcumin -- the substance that gives Indian curry its bright color -- improved memory and mood in people with mild, age-related memory loss, according to the results of a study conducted by UCLA researchers.

The research, published online Jan. 19 in the American Journal of Geriatric Psychiatry, examined the effects of an easily absorbed curcumin supplement on memory performance in people without dementia, as well as curcumin's potential impact on the microscopic plaques and tangles in the brains of people with Alzheimer's disease.

Found in turmeric, curcumin has previously been shown to have anti-inflammatory and antioxidant properties in lab studies. It also has been suggested as a possible reason that senior citizens in India, where curcumin is a dietary staple, have a lower prevalence of Alzheimer's disease and better cognitive performance.

"Exactly how curcumin exerts its effects is not certain, but it may be due to its ability to reduce brain inflammation, which has been linked to both Alzheimer's disease and major depression," said Dr. Gary Small, director of geriatric psychiatry at UCLA's Longevity Center and of the geriatric psychiatry division at the Semel Institute for Neuroscience and Human Behavior at UCLA, and the study's first author.

The double-blind, placebo-controlled study involved 40 adults between the ages of 50 and 90 years who had mild memory complaints. Participants were randomly assigned to receive either a placebo or 90 milligrams of curcumin twice daily for 18 months.

All 40 subjects received standardized cognitive assessments at the start of the study and at six-month intervals, and monitoring of curcumin levels in their blood at the start of the study and after 18 months. Thirty of the volunteers underwent positron emission tomography, or PET scans, to determine the levels of amyloid and tau in their brains at the start of the study and after 18 months.

The people who took curcumin experienced significant improvements in their memory and attention abilities, while the subjects who received placebo did not, Small said. In memory tests, the people taking curcumin improved by 28 percent over the 18 months. Those taking curcumin also had mild improvements in mood, and their brain PET scans showed significantly less amyloid and tau signals in the amygdala and hypothalamus than those who took placebos.

The amygdala and hypothalamus are regions of the brain that control several memory and emotional functions.

Four people taking curcumin, and two taking placebos, experienced mild side effects such as abdominal pain and nausea.

The researchers plan to conduct a follow-up study with a larger number of people. That study will include some people with mild depression so the scientists can explore whether curcumin also has antidepressant effects. The larger sample also would allow them to analyze whether curcumin's memory-enhancing effects vary according to people's genetic risk for Alzheimer's, their age or the extent of their cognitive problems.

"These results suggest that taking this relatively safe form of curcumin could provide meaningful cognitive benefits over the years," said Small, UCLA's Parlow-Solomon Professor on Aging.

Journal Reference:

1.Gary W. Small, Prabha Siddarth, Zhaoping Li, Karen J. Miller, Linda Ercoli, Natacha D. Emerson, Jacqueline Martinez, Koon-Pong Wong, Jie Liu, David A. Merrill, Stephen T. Chen, Susanne M. Henning, Nagichettiar Satyamurthy, Sung-Cheng Huang, David Heber, Jorge R. Barrio. Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin in Non-Demented Adults: A Double-Blind, Placebo-Controlled 18-Month Trial. The American Journal of Geriatric Psychiatry, 2017; DOI:10.1016/j.jagp.2017.10.010

Peter

[pjoshea13 in reply to petercraig2]

Peter,

The study used Theracurmin, which is new to me [1].

I use LongVida which has also been shown to affect brain function. NOW sells it as CurcuBrain [2].

Bioavailabilty of curcumin is a big issue. I know that some put their faith in turmeric, which is dirt cheap but has poor bioavailability. The two products clearly cross the blood brain barrier (a big hurdle), so might get to PCa cells.

-Patrick

[1] swansonvitamins.com/swanson...

[2] swansonvitamins.com/now-foo...