A PCa study involving apigenin has been appearing roughly every 2 months this past 18 years. A bit frustrating, since while apigenin is found in many plants (celery, parsley & chamomile flowers are good sources), no-one saw fit to create a product until a few years ago. The only one I'm aware of is:
swansonvitamins.com/swanson...
(derived from grapefruit) From the blurb:
"You may not have heard about this once obscure bioflavonoid, but a quick Google search will show you that Apigenin is poised to become a well-recognized nutrient. Researchers are investigating its potential to promote cellular health within various tissues. The most promising work is being done with regard to the prostate ..."
Unfortunately, I can't think of a way to present the PCa research without using some alien-sounding terminology. But, scattered in the following will be smatterings of English. Even so, I have limited my selection to 6 studies.
These are all cell/mouse studies, & some find such to be less than compelling, but apigenin is such a versatile polyphenol, & seemingly well-suited to PCa studies, that I'd be dismayed if it had no benefit at all.
[1] (2016 - China)
"Apigenin inhibited human 3β-hydroxysteroid dehydrogenase..." This is the enzyme involved in "the biosynthesis of progesterone from pregnenolone, 17α-hydroxyprogesterone from 17α-hydroxypregnenolone, and androstenedione from dehydroepiandrosterone (DHEA) in the adrenal gland" (Wiki)
Apigenin also "inhibited human ... 17β-hydroxysteroid dehydrogenase 3 ..." This is an enzyme involved in the "interconversion of DHEA and androstenediol, androstenedione and testosterone, and estrone and estradiol, respectively" (Wiki)
Apigenin might therefore be a useful androgen inhibitor.
[2] (2015 - Cleveland, US)
The cause of the creation of pro-cancer inflammatory metabolites of the omega-6 arachidonic acid, is the activation of nuclear factor-kappaB [NFkB]. NFkB exists in cells in an inactive state. It is tied to a protein. PCa cells produce IKKα, which unhooks the protein, leaving NFkB free to move to the nucleus & generate a large number of survival proteins. NFkB is a prime target in PCa.
"IKKα has been implicated as a key regulator of oncogenesis and driver of the metastatic process; therefore is regarded as a promising therapeutic target in anticancer drug development. In spite of the progress made in the development of IKK inhibitors, no potent IKKα inhibitor(s) have been identified. Our multistep approach of molecular modeling and direct binding has led to the identification of plant flavone apigenin as a specific IKKα inhibitor. Here we report apigenin, in micro molar range, inhibits IKKα kinase activity, demonstrates anti-proliferative and anti-invasive activities in functional cell based assays and exhibits anticancer efficacy in experimental tumor model."
"Overall, our results suggest that inhibition of cell proliferation, invasiveness and decrease in tumor growth by apigenin are mediated by its ability to suppress IKKα and downstream targets affecting NFĸB signaling pathways."
[3] (2015 - Davis, CA, US)
Drug resistance is common in PCa. There are various mechanisms, including ABCB1 efflux. (Don't ask!) Anyway, a 2015 paper reported that Casodex & Xtandi (both antiandrogens) could resensitize PCa to Taxotere by inhibiting ABCB1 efflux.
The [3] paper reports that:
"ABCB1 transport activity can be mitigated by the phytochemical apigenin and by antiandrogens such as bicalutamide {Casodex}, with each improving cellular response to chemotherapeutics."
[4] (2015 - India)
Velcade (bortezomib) is part of the standard treatment for multiple myeloma. It is a proteasome inhibitor. Apigenin has some proteasome activity. Anyway, cutting to the chase:
"Apigenin selectively inhibits proteasomal degradation of tumor suppressor ER-β"
"Unlike bortezomib, apigenin's actions are subtle, precise, mechanistically distinct and capable of abstaining drug resistance."
ER-β is the protective beta estrogen receptor that is often lost in PCa cells at an early stage. Apigenin will not restore ER-β, but it may inhibit its degradation.
[5] (2014 - Cleveland, US)
A fascinating aspect of more recent research is the finding that many of the changes that occur in prostate cells during the transformation to PCa are epigenetic. The genes are not mutated, but are silenced. One way this occurs is by preventing access to protective DNA regions. DNA is stored as a tightly folded ball, & histones facilitate the wrapping. Acetylation of the histones is necessary for loosening & giving access to the DNA areas. However, HDAC (histone deacetylase) in PCa cells prevent this.
To put this in perspective, ClinicalTrials.gov has 19 study hits for <prostate HDAC>. e.g. one paired Casodex with Panobinostat (a histone deacetylase inhibitor).
Back to [5]: "Apigenin treatment resulted in the inhibition of class I histone deacetylases and HDAC1 protein expression ..."
"... apigenin treatment led to decreased HDAC1, causing increased acetylation and disruption of Ku70–Bax interaction, thereby releasing Bax in the cytosol. Apigenin-mediated increase in Bax levels promotes apoptosis in prostate cancer cells."
Bottom line: apigenin inhibited the epigenetic silencing of Bax, which promotes PCa cell death.
[6] (2012 - Cleveland, US)
Insulin-like growth factor I [IGFI] is implicated in aggressive PCa. The literature is extensive.
"The IGF axis plays a major role in prostate cancer development and progression. As neoplastic prostate epithelial cells progress to an organ-confined, androgen-dependent prostate adenocarcinoma, IGF-1 secretion from prostate stromal cells increase, and epithelial cells begin to express and secrete IGF-1; additionally, IGF-1R becomes over-expressed on the plasma membrane of the prostate cancer cells and on stromal and epithelial cells adjacent to the tumor [2]. Due to increased secretion of proteases from the prostate tumor, IGFBP-3 protein levels within the tumor microenvironment decrease significantly [2, 5, 48]. These alterations result in increased IGF-1R signaling essential in androgen-dependent prostate cancer for cell proliferation and tumor growth, enhanced metabolic activity, and apoptosis avoidance [2, 5, 48]. The IGF axis is also critically important in the transition of organ-confined, androgen-dependent prostate cancer to more aggressive forms, such as metastatic and androgen-independent prostate cancer [45, 52–54]. In androgen-resistant and metastatic prostate cancer, the IGF-1R is even more over-expressed and signals in an androgen-independent manner through the PI3K/Akt signaling pathway to promote growth, proliferation, and migration [45, 52–54]. Additionally, the IGF-1 ligand and its downstream effector, Akt, appear to be important in the promotion of AR activation in the absence of androgens, allowing tumor survival and proliferation after androgen withdrawal [3]. Apigenin, a natural anticancer agent, has been shown to target the IGF axis and its intracellular signaling in androgen-responsive, androgen-resistant, and androgen-independent prostate cancer cells [6, 83–86; Figure 1]. Oral consumption of apigenin has been found to increase circulating and prostate tumor IGFBP-3 levels [84, 86], decrease circulating and prostate tumor levels of IGF-1 [84, 86], inhibit IGF-1R activation and downstream signaling in prostate cancer tumors [50, 83, 86], and induce cell cycle and growth arrest and apoptosis of prostate cancer cells and tumor xenografts without harming normal tissues or causing toxicity in pre-clinical in vivo TRAMP and xenograft mouse models [83, 86, 87]."
-Patrick
[1] ncbi.nlm.nih.gov/pubmed/271...
[2] ncbi.nlm.nih.gov/pmc/articl...
[3] ncbi.nlm.nih.gov/pmc/articl...
[4] ncbi.nlm.nih.gov/pubmed/254...
