Darpan I. Patel, PhD, Associate Professor of Research in the School of Nursing at The University of Texas Health Science Center at San Antonio and Pratap Kumar, PhD, Professor of Molecular Medicine at The University of Texas Health Science Center at San Antonio, talk about their research showing how tree bark extract slows the growth of prostate cancer.
In testing the control group, the exercise group and the cork tree bark group, what were the three conclusions so far?
Professor Patel: The three conclusions that we came up with as a matter of the outcomes of the study were that – one, that Nexrutine, the Phellodendrom amurense extract, and exercise are both similarly able to reduce tumor aggressiveness. So that’s first and foremost. The second answer that we came up with was that, while they’re able to promote the suppression of tumor aggressiveness, they do so we believe in different pathways. What I mean by that is that Nexrutine, the Phellodendrom amurense extract, we thought, based on the results that we found, to be more predominantly impacting the growth signaling pathways of the tumor, meaning that it’s actually – that where the tumor grows in mass and the tumor accelerates it’s aggressiveness through the growth pathway – that was inhibited with the Nexrutine. Whereas, on the flip side, exercise did more of its impactful work through inhibiting pro-inflammatory cytokines or tumorigenic cytokines. And so, we found though they did suppress tumor aggressiveness, they did so in two separate pathways. And the third answer that we came up with was that there were no toxicities associated with the consumption of this natural product within these animals. And in fact, what we also found that’s probably more impactful was that there were less metastatic lesions, which also corroborates the fact that there was less tumor aggressiveness with the natural product and exercise compared to the control groups alone. So, what we found was that, with Nexrutine, we saw that Nexrutine significantly impacted the growth-signaling pathway, whereas with exercise we saw that exercise significantly impacted the pro-inflammatory or tumorigenic pathways. And so, while they were able to suppress tumor growth equally and tumor aggressiveness equally, we believe that they’re going to do so in different pathways.
Combining those pathways – and I assume that’s a future study, or are you still studying that now?
Professor Patel: We’re in the process of beginning that study in the next month or so. COVID-19 kind of put a stop to that unfortunately. So, we would be in the middle of that product right now. But what we plan to do is, once everything becomes the new normal, is initiate another preclinical study combining the two interventions together to see if there’s an additive effect where we can hit both pathways at the same time and hopefully get an additive effect in further suppressing tumor aggressiveness.
I know you start with hypotheses at the very beginning, but do you necessarily anticipate an outcome like this? That one goes down that path and the other one goes down the other path?
Professor Patel: I thought that the exercise would also suppress tumor growth through the growth factor pathway. But in retrospect, that probably was not the best hypothesis to come up with because exercise in and of itself is a growth factor – growth hormone stimulating type of intervention. And so while we – our initial – my initial hypothesis in that it would suppress tumor aggressiveness through inflammation suppression as well as growth factor suppression was only half correct, such that we were able to see exercise inhibiting the inflammatory process and not so much the growth factor signaling.
Why is exercise good for you?
Professor Patel: Exercise in and of itself is a very significant anti-inflammatory intervention. Just by walking 30 minutes a day, five days a week, research has found that you were able to suppress a lot of the pro-inflammatory cytokines that are associated with multiple morbidities and mortality issues such as cancer, such as diabetes, such as cardiovascular health. We also know that the very minimal amount of exercise can improve cognition, improve memory, improve physical function and ultimately improve quality of life. But one of the underlying mechanisms as to why exercise is so good for us is because it has this anti-inflammatory component which is natural to the intervention, and that’s why we consider exercise to be an anti-inflammatory intervention because that data does show that we’re able to suppress pro-inflammatory cytokine activity and increase anti-inflammatory cytokine activity at the same time.
What does inflammation look like?
Professor Patel: Inflammation is very much a complicated process. It’s not the physical inflammation that we think of when we twist our ankle or hurt our joint. That’s a good inflammation as well, where the fluid is coming to that joint to protect the joint from further damage. But when we think about inflammation, we think about systemic inflammation in that we see an increase in these pro-inflammatory cytokines, which is known to trigger downstream effects which can be detrimental to the healthy body if we experience it for long periods of time. In the acute setting, where we hurt ourselves and we see an increase in these pro-inflammatory cytokines, that’s a good thing. But if you have a constant increase or a new steady state of pro-inflammatory cytokines where you’re at a higher level every year of your life, that’s actually a bad thing because pro-inflammatory cytokines have been associated with heart disease, have been associated with cancer, have been associated with neurological issues – dementia, Alzheimer’s – and so we want to be able to suppress the activity of these pro-inflammatory cytokines as much as we can throughout our lifespan. And by having a healthy, active lifestyle – also a healthy diet can suppress the activity of these pro-inflammatory cytokines in our body and make us healthier.
Can a Physician tell that they’re not going to do as well as somebody who’s really following the rules?
Professor Patel: I don’t think we have enough evidence right now to really make that sort of conclusion. What my physician colleagues do talk to their patients about is maintaining a healthy, active lifestyle. And whatever that is to that individual is very personalized. And so, we can’t necessarily go out and tell everyone to do the same thing because, just like chemotherapy, radiation therapy, exercise is very much individualistic intervention. It’s not a one-size-fits-all. And so while it’s very important to have these conversations with the physician and with the patients, it’s a multiple number of issues that really impede these conversations from happening because you can’t just talk about exercise in a typical 15-minute physician’s visit because, with a cancer patient, there’s so many other things that the physicians need to cover in that small amount of time that they have with the patient. And so that’s why I think, as we move forward – as we have more evidence on the benefit of exercise in the oncology setting, in the rehab setting for oncology patients – and what we’re doing here at the Mays Cancer Center is actually starting to think about the pre-habilitation of patients prior to the onset of chemotherapy and radiation therapy to help them overcome some of the detrimental side effects. But what I’m trying to say is that what we need is a more holistic team-based approach as we move forward because the physicians don’t have the time, physicians don’t necessarily have the adequate training to really have these precise conversations on how to develop an exercise prescription for their oncology patients. That’s where exercise physiologists, oncology exercise specialists – that’s where we come in and really help fill that gap. But, ultimately, it takes a very much integrated, comprehensive team approach. And honestly, we’re just not there right now in our health care system nationally to be able to do that because of multiple reasons, but I’m hoping, as we develop more and more evidence onto the benefit of what exercise is able to do, what healthy diets are able to do for our oncology patients, that we’re going to start moving closer towards a comprehensive team-based approach to managing the health and wellness of our oncology patients.
During this study, what diagnostic tools did you use to show improvement?
Professor Patel: At the time of sacrifice, we excised the tumors from these mice. And we analyzed the tumor tissue the same way tumor tissue would get analyzed from a clinical patient – from actual prostate cancer patients that they went to the pathologists. The pathologists reviewed these tumor slides and they graded it just the same way they would have graded the tumor pathology slide from a cancer patient. The trademark name, when it was available over the counter, was Nexrutine. And so, a lot of the early publications and in fact, in this recent publication that we had as well, we referred to it as next routine because we were able to get it from the vendor that was manufacturing and distributing locally. But because that vendor had a refocusing of their mission for their company, they’re not distributing Nexrutine the way they used to. And so, I used the actual name, Phellodendrom Amurense, which is the geneology name for the cork tree extract as the actual product now. As we move forward, because Nexrutine is not available over the counter as readily as we hoped it would be, we’re getting the pure extract from some vendors in China, and that’s where we get it from. So that’s why I referred to it specifically by Phellodendrom Amurense.
What would you say to somebody who says, well, I’m going to run out right now and buy some cork tree extract and get on my treadmill?
Professor Patel: What I would caution individuals from doing is running out and getting natural supplements and natural products thinking that it’s going to be a end-all cure-all for their condition. First and foremost, a conversation needs to be had with their physician – their managing oncologist to determine what is safe to take and to determine whether exercise is going to be beneficial to them. Because there are a number of – so there are a number of contra-indications to people from – for people to participate in exercise, meaning that there are conditions where exercise may not be good for people – because of physical limitations, because of medical conditions and so on and so forth. And so before anyone starts to begin an exercise intervention or think about taking over-the-counter supplements, they need to have a very in-depth conversation with their oncologist, with their physician to determine whether or not these products or even participating in exercise is going to be healthy and beneficial to you.
What’s the timeline on where you are with animal trials versus human studies?
Professor Patel: We’re going to initiate the next animal trial for this Nexrutine and exercise combination in the next few months, once we get to our brand new normal. And then the plan for that is to really understand what the underlying mechanisms are with respect to studying the tumor genome and seeing where within the tumor genome our intervention’s having a significant impact. Like we’ve talked about before, we know that exercise is good for us. We know that supplements, if taken effectively, can also be good for us as well. Like, for example, we know exercise is good for the heart, it’s good for the brain, it’s good for muscles, good for bone – good for the body head to toe for the most part. What we don’t know is the how. Like, what is going on within our body in response to exercise that’s causing some of these benefits? And what we’re going to be doing with this next round of research is really getting down to the molecular level – to the genetic level and understanding where our interventions are actually having an effect, and specifically looking at the tumor genome we’ll be able to see what specific genes within the tumor are increased or upregulated, we’ll see what genes are suppressed, so that we have a better idea of where we need to focus our attention moving forward. And I anticipate, over the next year or so, we’ll be initiating early phase clinical trials to study the effect of not just exercise but the Nexrutine and this natural product on its effect on tumor suppression. And there’s a number of different ways that we anticipate doing these interventions, but within the year I believe that we’ll be able to initiate clinical trials with hopes that about two or three years from now we’ll have the first reports out showing how Nexrutine is able to impact prostate tumor aggressiveness in actual clinical trial data.
Pratap Kumar, PhD, Professor of Molecular Medicine at The University of Texas Health Science Center at San Antonio.
Who knew that exercise was this important?
Professor Kumar: We all know that exercise in important. But we really don’t fully understand (scientific evidence) how it benefits. So, exercise really benefits not necessarily only cancer, but other pathological abnormalities. So, it is going to benefit.
I think people look at all this information and you read on the web and everything, but they can’t see it. So how do you define that to them?
Professor Kumar: It’s exercise, not medicine. To really show the benefit of exercise randomized controlled studies should be conducted with large number of patients. So that is where these preclinical studies, come in to play where we can conduct initial, what we call as proof-of-evidence studies to show how it benefits. So, we provide that evidence that would lead to large, randomized studies in humans where we can show the benefits of exercise. Exercise is not necessarily going to cure cancer but at least if it’s going to delay that or if it reduces the pathological aggressiveness of cancer, that’s a big benefit for the patient. So that’s going to increase their survival and improves their quality of life. That is the major impact it will have.
Exercise works the heart; it gets the blood pumping. All those things counteract cancer.
Professor Kumar: Not necessarily. Basically, in our body we have a lot of molecules called inflammatory cytokines. These are the protein molecules that cause inflammation. There are two different types of inflammatory molecules. One is pro inflammation which is basically causes inflammation, which is not good. At the same time, you also have an anti-inflammatory molecules which reduces the inflammation. So that’s why it reduces the pain and if you feel pain in your head, headache for example, why that does happen? Or pain in your leg, why does it happen? One possible reason is there is an inflammation in that area. Once it subsides, that goes down. So, there are a lot of molecules that are involved in causing this inflammation. Inflammation is the key driver for many pathological diseases, whether it is cancer or Alzheimer’s or cardiovascular diseases. It’s the central hub. It causes a lot of these things. So, if you can target that, there is a benefit for a lot of these diseases.
You have three groups. So how did all that work and what about the cork tree bark?
Professor Kumar: Our lab has a passion for working with natural products. So, the reason for that is there is extensive amount of evidence from literature, which is called epidemiological evidence, showing that people consuming fruits and vegetables tend to have a lower risk for cancer and other diseases. We started working with these natural products. One of them is this nexrutine or cork tree extract, which we have been working on for the past 20 years. So how did we find that? It’s sold over the counter as an anti-inflammatory agent. So, people have been buying and using it for their inflammatory diseases, especially for joint pains. And a company that was selling these pills were informed that some of the consumers actually reported to them that it decreased their prostate specific antigen (PSA) levels, which is a marker for prostate cancer. So, at that point, they had no clue, why would it do that? Because they were selling it as an anti-inflammatory. That’s where we got into picture. For whatever reason, they contacted me because we have been working in the prostate area. They asked do you think this is going to help or is it a benefit for prostate cancer patients? I told them I have no idea. Basically, this could be just random coincidence. I mean, you have some consumers taking it and there is no real scientific proof. But we work in that area, so I’m interested in pursuing this. So that’s when we started working with this company. We got the extract. We started with cell culture models in the lab and then went to animal models, and we saw, to our surprise, that it does decrease their prostate cancer progression. So, we knew it is doing something there. So that’s how this started. So then how did you end up in doing exercise, right? So, if you look at cancer patients or cancer survivors, they’re all older patients. I mean although you know the benefit of exercising, they may not have the energy to do that or they don’t like to do that. Or they may be undergoing some treatments that may be impacting their ability to really do exercise, so there are a lot of factors that affect why you may not be able to do that. So that’s when I ran into Dr. Patel who is an exercise physiologist – a great expert in that area. So, we discussed about what can we do to benefit these people? Because like I told you, this extract decreases inflammatory molecules. Published literature suggests that exercise does modulate those inflammatory markers. So, we felt, why can’t we just compare these two (Nexrutine and exercise) and see what happens? The idea behind that is whether we can replace exercise with these pills. For example, people, cancer survivors and older people with cancer, if they don’t want to or they cannot do exercise, hopefully by taking these kind of pills, they might get the beneficial effects of exercise. That’s the real, long- term goal.
If you combine these two together, the cork tree and the exercise, you have a double whammy. What if somebody just decided to do one or the other and not mix them?
Professor Kumar: You could do that, but right now we really do not have any evidence. What evidence we have is this animal study. We took three different groups of mice. We randomized them. One group received this extract, second group of animals were subjected to voluntary exercise. These mice sit down at the wheel (kind of treadmill) and they just turn the wheel around and that’s how they get exercise. And the other group just a control group. No treatment, nothing. And when we compared pathologically, surprisingly both groups got similar benefits in terms of reducing the pathology – close to 60 percent reduction. The control group developed aggressive prostate tumors. On the other hand, these two groups receiving Nexrutine or exercise developed what we call high grade pin lesions which is an early lesion. But it’s not cancerous which is good. So, we know that the benefit we got from this extract is similar to exercise in this model. When we looked at it mechanistically of how exactly this is happening, it turned out that both appear to work differently. In other words, they change different inflammatory molecules. So obviously they’re not working through the same pathway. So, if you combine those two for example, it is possible to see double the benefit.
What is cork tree bark? And there are so many natural supplements. People are divided on whether they should take it or should they stick to what the doctor prescribes?
Professor Kumar: There’s a big debate about that. First of all, to answer your first question, what is cork tree extract? This tree is native to eastern Asia. You see this tree mostly in China. So, there is anecdotal evidence for using this extract in number of ailments (joint pains, diaherea etc.) in Traditional Chinese Medicine. They make a decoction out of this bark. And they drink the concoction. But they claim it reduces their dysentery. There is no scientific evidence for that. That’s what we provided. The scientific proof that the cork tree extract is doing something in terms of cancer prevention or reducing cancer progression. And before our studies, nobody really explored this in terms of its benefit for cancer management. And we wouldn’t have started unless we received that phone call from the CEO of this company giving this us non-scientific evidence of what is happening in consumers, in terms of prostate cancer. So, there are a lot of natural products on the market. Which one to choose, what to use and what to do, what not to do. However, there are number of challenges with these natural products. They are good. Unfortunately, for most of these products scientific proof is lacking. So, if I had to take something like that, I would look for that kind of information. So, whether or not it has any scientific evidence showing that it has some beneficial effects, not necessarily preclinical but some clinical evidence, I think that is what’s important.
What do you hope to see out of all of this at the end of the day?
Professor Kumar: Both Dr. Patel and I, we really want to see this help patients. That is our major goal. And we will go beyond prostate to other types of cancers – breast cancer, cervical cancer, liver cancer – because exercise benefits every single individual. So that is what we are trying to provide through this study what we call the proof of concept to show that this extract provides benefits similar to exercise at least in the model we tested. This current study is not without limitations, we will continue these using different models and expand to other models including combining both exercise and Nexrutine.
Would you tell people this is interesting because this extract is already out on the market? Would you tell people to start taking it? Or would you stop short of that?
Professor Kumar: We ask them to consult their physician and show them these publications. So, it’s up to the physician whether they would suggest it to the patient because each patient is different depending on their condition. I mean we provided evidence through preclinical study and there is some clinical evidence that it is safe and tolerated in patients. That information is published. A physician can look at that information and help the patient with decision. This is important as we really don’t know if this extract interferes with other drugs and how it affects the patients.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
Rosanne Fohn, Public Relations
The University of Texas Health Science Center at San Antonio
Sign up for a free weekly e-mail on Medical Breakthroughs called First to Know by clicking here
