synergistic effect of milk thistle and licorice?
in vivo but maybe worth a try? - Fight Prostate Ca...
in vivo but maybe worth a try?
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Maxone73
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Be careful. Too much liquorice can increase blood pressure.
this article is behind a paywall
We have to wait for another publisher or I might ask here:
Here is a NIH article from 2017 that shows natural combination of compounds Usolic acid + curcumin and reverstrol against PCa on mouse models using PCa cell lines.
ncbi.nlm.nih.gov/pmc/articl...
Combinatorial treatment with natural compounds in prostate cancer inhibits prostate tumor growth and leads to key modulations of cancer cell metabolism
Discussion
In this study, we screened a library of natural compounds for efficacy on the survival of PCa cells. We performed a primary screen based on depletion of cellular ATP levels. Cellular ATP levels are critical for cell survival, and several reports have shown that reductions in cellular ATP levels can lead to apoptosis and other types of cell death in cancer cells, depending on the level of depletion.38–42 Based on cell viability (from ATP levels) of the primary screen, we selected the top hit natural compound (UA) and performed an additional secondary screen to investigate the effect of the administration of the top hit in combination with the natural compounds in the library. Notably, UA had previously been shown to deplete ATP in a glioblastoma cell line leading to necrotic cell death43 and to exert anticarcinogenic properties in several animal models of cancer.18, 44–46
For the secondary analysis, we screened both cellular ATP depletion levels and induction of ROS. Induction of ROS has been previously associated with reduced tumor cell growth for a number of tumor types.47 From the secondary screens, we identified two additional compounds of interest (CUR and RES) that induced marked reductions in cellular ATP levels when administered in combination with UA. CUR and RES have both been widely studied as chemopreventive agents.7, 48, 49 Clinical trials have been conducted with both CUR and RES administered as single agents for cancer chemoprevention.50–52 In particular, CUR has been studied in a number of clinical trials, either completed or ongoing, for a variety of cancers, including solid tumors.53 In line with the results of previous reports,16 CUR alone promoted increased ROS. However, all the other individual treatments (UA and RES), as well as the combination of both CUR and RES with UA either had no effect or induced drops in ROS levels depending on the PCa cell line. Therefore, the combined treatment efficacy observed in thisin vitro study is likely not determined by induction of ROS but has an alternative molecular origin. Before moving on to a more detailed investigation of the molecular mechanism of action of the selected natural compounds, we validated the effect of the combined treatments on tumor growth in a mouse allograft model of PCa. The in vivo studies provided further evidence that the selected natural compound combinations were highly effective in slowing growth of murine PCa cells. Notably, all the combinations of the selected natural compounds led to synergistic effects on tumor volume and weight (according to the Bliss index); in all cases, the combined administration of these natural compounds produced tumors of much smaller size than in untreated mice or mice receiving the individual compounds, with the combinations of UA with either CUR or RES yielding the best results.
Additional analysis of the treatment induced metabolic changes revealed a strong influence of both the combinations of UA either CUR or RES on glutamine/glutamate-related metabolic pathways. Metabolic analysis of the flux of isotopically labeled glutamine pointed to a decreased glutamine uptake from the extracellular space in cells treated with UA in combination with CUR or RES. Notably, the dependence on increased amino acid transport (i.e., increased expression of the amino acid transporters) for prostate cell growth has been previously reported, as well as the hindered PCa cell growth following inhibition of the ASCT2 glutamine transporter.54, 55 In our study, the levels of ASCT2 decreased following treatment with UA alone as well as its combinations with either CUR or RES. Moreover, the combination of CUR + RES also resulted in decreased levels of ASCT2 (although less dramatic than for the other combinations). Therefore, the modulation of ASCT2 alone did not fully explain our observation of glutamine metabolism nor the possible association with the improved in vivo outcome.
Recent studies reported that glutamine mediates oncogenic transformation in highly invasive ovarian cancer cells through STAT3 signaling.56 Given the decreased cellular uptake of glutamine resulting from the combined treatments with UA + CUR and UA + RES, we performed Western blotting to probe the level of phospho-STAT3. All three phytochemical combinations decreased the phosphorylation of Stat3 at both serine and tyrosine residues. Similarly, all three combinations also decreased phosphorylation of Src, in line with previous studies that also reported the decrease in Src phosphorylation in cells under conditions of both glutamine and glucose deprivation.56 Our additional mechanistic studies revealed a decrease in mTORC1 activity by the combination of phytochemicals. In this regard, Wang et al. showed that knockdown of ASCT2 by shRNA in PC-3 cells decreased the mTORC1 activity (measured by p70S6K phosphorylation) both in culture and in xenograft tumor tissues.54 Finally, as UA and the combinations decreased the cellular ATP level and depletion of cellular ATP level is associated with AMPK activation (reviewed in),57 we also measured the AMPK phosphorylation after treatment with the individual agents or their combinations. The combinations of CUR + UA and CUR + RES induced AMPK activation compared to untreated samples or treatment with the individual agents. Activation of AMPK might also be associated with the observed decrease in mTORC1 activity. Overall, as is expected for natural compounds, the outcome induced by the individual and, even more so, the combined treatments is due to complex effects entailing several cellular targets and pathways. While additional molecular targets are likely to further contribute to the beneficial effect of treatment with the selected natural compounds, the metabolic effect on glutamine metabolism and the associated effects on several key signaling pathways (STAT3/Src, mTORC1 and AMPK) likely contributed to the induction of apoptosis observed in HMVP2 cells in vitro and the synergistic inhibitory effects on tumor growth observed in vivo.
In conclusion, an initial screening approach has been developed to identify potential synergistic phytochemical combinations with chemopreventive/therapeutic efficacy for inhibiting growth of PCa and possibly other cancer cells. The ability of combinations to synergistically inhibit tumor growth was linked to synergistic changes in glutamine metabolism, the associated modulation of STAT3/Src, mTORC1 and AMPK signaling, and induction of apoptosis.
Hi! I am stopping ursolic acid (I still have some capsules) because there is not yet a nano formula that can increase its blood levels. Basically from the trials I have read it’s impossible to reach significant levels of UA in the blood. Curcumin I use Novasol formulation that should be the most available I have found in studies.
A1 Vitality curcumin brand also comes out on top for bioavailability, as per Consumer Labs
It’s still novasol. Novasol is not a brand it’s a technology, used also by A1 vitality
Thanks!
Im not wasting my limited resources (brain capacity) on that right now with so much new research out and trying to keep up with Maxone’s posts lol
