Influence of Cholesterol on Cancer Progression and Therapy - Translational Oncology - Volume 14, Issue 6, June 2021

[cujoe]

From early on in my cancer journey, I have been interested in the role of cholesterol in cancer(s), of which I have two, PCa and CLL. Cholesterol seems to be a major player in both of them. It is also one of my 4 Horsemen of the PCa Apocalypse (so named by Don Pescado) of Glycolysis, Inflammation, Cholesterol, and Hormone Balance.

This summary research article is the best explanation I have come across that describes cholesterol's role in cancer. It is quite technical for those of us who are not trained bio-chemists and is not completely specific to PCa, but even for those who do not care to delve into the complete metabolic actions that take place, it is still packed with insights that we can each use to make decisions about treatment options, scrip drugs, supplement choices, and aspirational diet and lifestyle goals.

This passage from the report highlights the need for all cancer patients to be knowledgeable about cholesterol:

"As evident from numerous studies including pre-clinical, clinical, meta-analysis, and population-based studies, cholesterol plays a vital role in cancer risk, progression, survival, prognosis, and therapy [[21], [22], [23],37,45]. Alteration in blood cholesterol level is a very common phenomenon in majorities of cancers [22,37,45]; however, it is still not clear for most of the cancers whether decreased blood cholesterol level in the cancer patient is a cause or consequence of the disease."

The illustrations in the report are first-rate and extremely useful in explaining in graphic form the roles of cholesterol in both normal and cancer cells. There is also a section that summarizes some treatment options for specific cancers. The research is mixed on the role of cholesterol in PCa. That section is reproduced in it's entirety below:

***

Prostate cancer

The relation between serum cholesterol and prostate cancer is complex. Few clinical studies indicate a link between high blood cholesterol towards increased risk of high-grade prostate cancer and the status of prostate specific antigen (PSA) [45,82]. The majority of epidemiological studies show weak evidence or no relation between blood cholesterol level and the risk of prostate cancer [83,84,85]. Even though the reports on the correlation of cholesterol with prostate cancer are conflicting, various studies suggest that non-identical races (black and white people) show a differential correlation between serum cholesterol and PSA levels. Increased blood cholesterol is highly correlated with increased PSA levels in the white population [86]. A population-based study from Stopsack KH, et al., demonstrate that lethal prostate cancer relies more on de-novo cholesterol biosynthesis instead of extracellular cholesterol uptake [87], whereas Singh G, et al., have shown up-regulated expression of LDLR in patient's tumor tissue samples. The increase in intracellular cholesterol inside the nucleus along with cyclin E overexpression in prostate tumor tissue indicates a potential role of cholesterol in regulating the cell cycle [88]. Also, metastasis of prostate cancer in bone causes an increase in cholesterol content as compared to the normal bone and these phenomena can be attributed to de novo cholesterol biosynthesis, supported by the influx of cholesterol through LDLR and SRB1 [89].

Studies in the xenograft model indicate the role of cholesterol in promoting tumor growth. Mice fed on a hypercholesterolemic diet with increased blood cholesterol level shows enhanced tumor progression along with induction of angiogenesis [90,91]. Moreover, in vitro conditions, upon treatment of prostate cancer cells with LDLc or cholesterol increased proliferation, migration, and invasion were observed [92,93,94]. Interestingly, prostate cancer cells lack a feedback mechanism for LDLR expression, even in the presence of excess LDLc, suggestive of the involvement of both pathways. In normal prostate cells, the expression of LDLR is tightly regulated and it decreases with an increase in LDLc availability [26]. Increased expression of LDLR is advantageous to prostate cancer cells as it facilitates enhanced uptake of fatty acids and cholesterol, which supports prostaglandin synthesis in cells [26]. Other than LDLR, Scavenger receptor class B type 1 (SRB1, HDLc receptor) was also found to increase in some prostate cancer patient samples [95]. Apart from these, androgen is required for normal epithelial prostate cell proliferation and differentiation. However, in advanced prostate cancer, cells can synthesize androgen by themselves in the presence of cholesterol, thereby making them self-sufficient for rapid cell division, independent of testicular and/or adrenal androgens [91,96].

Above mentioned studies illustrate both positive and negative correlation of cholesterol with prostate cancer. Clinical and preclinical studies highlight the role of cholesterol metabolism and LDLR in enhancing prostate cancer cell proliferation. The differential findings in clinical studies might be contributed in part by variability in the race and hormonal status, which needs further exploration.

***

The full report is here:

Influence of cholesterol on cancer progression and therapy

Translational Oncology - Volume 14, Issue 6, June 2021, 101043

sciencedirect.com/science/a...

Of special note to all prostate cancer patients is the following research on statins and PCa that is footnoted in the paper. It provides a caution to those who are taking satins as part of a treatment plan (self-directed or otherwise). It might cause you to take pause and reconsider whether that is a zero-risk strategy. Granted, the initial research was done in-vitro and in mice, but the follow-up patient profile study seems to suggest that there is, at a minimum, a sub-set of patients whose PCa could be made more aggressive by the use of statins. I suggest that anyone using them should read the entire report and come to their own conclusions.

That research (full report) is here:

Low-dose statin treatment increases prostate cancer aggressiveness

Oncotarget. 2018; 9:1494-1504

oncotarget.com/article/2221...

Be Informed and Stay Well, K9

[NPfisherman]

K9 Wonder,

Good information for everyone on the forum. I take Atorvastatin 80 mg for hypercholesterolemia and it keeps my LDL down and HDL up. For those that have CV risks, controlling your cholesterol is essential. More people die of stroke or heart attack than PCa.

Interesting that newer cholesterol drugs Ezetimibe and Avasimibe showed efficacy against PCa. I do wonder if PCSK9 inhibitors have been tested against cancer. There are other new cholesterol drugs out like bempedoic acid....Watching this area with much interest...

Thanks for posting....

Fish

[6357axbz in reply to NPfisherman]

I too take 80 mg atorvastatin for the same reason as you Fish. All I’ve heard to date is there is a possible PCa benefit to the use of statins.

[cujoe in reply to 6357axbz]

axbz,

The possibility that "low-dose" statins could be bad for PCa was what I "remembered" as being news to me, too. However, a quick search at "that other" HU PCa forum indicates that Karmaji did post about this a month back. After a quick review of the first several replies, I do now remember seeing the post, but likely did not actually read the research. (My bad!)

So, it is probably worth reviewing that thread for context. As stated in the post above, the basic research is not on human subjects and the observation study conclusions are not dose-dependent, so grain of salt is in order. I, for one, rarely discount the possibility that any research may have uncovered some new information that I need to consider. Confirmation bias is a powerful agent in causing us to look away from the very things we need to see. We all fall prey to it no matter how open-minded we like to think we are.

K9

[cujoe in reply to NPfisherman]

Thanks for the input, NP,

My personal issue is with low HDL. Last year I went back and looked to 2003 for at the earliest lipid panel I had records for. I saw that it was also low-normal way back then. I now believe it was an indication that my CLL was already active. Although, it would be 3 years later that I was diagnosed via a biopsy on an enlarged neck lymph node.

Cholesterol apparently plays a larger role in CLL than PCa and an HDL drop can be an early sign. My HDL was sub-normal on my last lipid panel (at 37), so I recently added a preferred brand of Red Yeast Rice along with niacin. I have also recently started running 3 miles X 3 times a week, as exercise is reported to help boost HDL. I see my PCP in two months, so I will be able to determine if those actions have gotten me at least back up in the normal range. Fortunately, I have no history (familial or personal) of cardiac issues, so I'm not overly concerned about the low HDL and that risk.

As usual, neither of my cancer oncologists have ever asked for or responded to my lipid lab numbers. I have upcoming appointments with both of them mid-year and I will see what, if anything, they say about the low HDL and either of my cancers. It seems, being our own best patient advocates, we are forever charged with making sure our MDs are paying attention to all the relevant information.

One particular I picked up from the research article is that only about 20% of our cholesterol comes from dietary sources and its metabolism is regulated by liver biosynthesis increasing or decreasing as necessary in response to dietary intake. So, it seems that the notion we can completely control cholesterol via diet & lifestyles is not really the case.

Now, where did I put that bacon & egg sandwich?

Y'all Stay Safe & Well, now . . . ya' here! Ciao - k9 terror

[NPfisherman in reply to cujoe]

K9,

Use the Butterball Turkey bacon--lower in sodium and cholesterol and fat.... There are newer cholesterol drugs including an injection 2x a year :

webmd.com/cholesterol-manag...

The combo of statin plus a PCSK9 ( a combo with a K9) reduced arterial plaque in 4 of 5 patients.... From the article:

Ultrasound scans showed that bringing cholesterol levels that low prompted hardening of the arteries to reverse in four out of five patients, Nissen said.

The Repatha study involved 846 patients with coronary artery disease. Half received statins alone, and others received the PCSK9 inhibitor and statins.

About 81 percent of patients taking Repatha and statins showed a reduction in arterial plaque volume, the results showed.

Now isn't that something???

Fish

[6357axbz in reply to NPfisherman]

I hope the trials pan out. Thanks for the post Fish!

[cujoe in reply to NPfisherman]

That IS something - and something I WILL keep in mind.

As far as I know, my arterial issues are from calcium deposits that showed up on the CT scans I had prior to going on my brief, but effective ADT treatment back in 2017. That finding got my attention. So, once I learned the value of magnesium, boron, Vit K & D, and of the possible benefits of nattokinase and serrapeptase (all Thanks to Nalakrats), I added/modified my supplement regime and diet to better reflect the processes that put calcium in the bones and not in the arteries and kidneys. Only time will tell if any of that will make a difference. Also (thanks to Patrick O'Shea), I do not supplement at all with calcium and keep my dietary intake well below the RDA of 1000 mg,

As you know, I lean strongly towards a WFPB, near-vegan diet (VERY long time since bacon & eggs hit my plate), so my dietary cholesterol is negligible. The sub-normal HDL is the current issue that I am working to increase. Lipids will be tested in a couple of months. If HDL has not improved, I will maybe see what a cardiologist thinks I should do. (If anything.)

Later K9

[Magnus1964]

I just started atorvastatin

And my PSA dropped 13 points.

[cujoe in reply to Magnus1964]

Anything else that might have caused or contributed to the drop?

[Magnus1964 in reply to cujoe]

Who knows, after my heart surgery they gave me a dozen other medications. But the cholesterol drug is only one that I am aware of the might affect PSA.

[cujoe in reply to Magnus1964]

Thanks for the response. Heart surgery - like PCa is not enough to deal with. Take good care of that ticker & Stay Well.

[NPfisherman]

Maybe you should do posts covering all of the Horsemen... I am looking at doing a post on the Bromodomain inhibitors--the next class of drugs outside of AR drugs for PCa...

Fish

[cujoe in reply to NPfisherman]

I actually considered doing that, but started with inflammation and fell down a medical knowledge rabbit hole. May look it over and see if I can give it another try "one of these days". Would be glad for you to beat me to it.