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How hispolon helps the immune system to kill cancer cells

Hispolon, a phenol found in the medicinal mushroom Phellinus linteus, is not just of interest to ergonauts who want to optimise their hormone balance for the sake of their athletic performance. The findings of a Korean in-vitro study, published in Oncology Reports in 2016, suggest that hispolon may also help the immune system to clear up cancer cells. And if hispolon is indeed capable of doing this, then there are many more naturally occurring substances that can do the same...

One of our immune system's jobs is to deactivate and clear up cancer cells - which are continually being created. A molecule that plays an important role in that process of elimination is tumor necrosis factor-related apoptosis inducing ligand [TRAIL]. [Cell Death Differ. 2004 Dec;11 Suppl 2:S122-5.]

How hispolon helps the immune system to kill cancer cells

How hispolon helps the immune system to kill cancer cells
Cancer researchers hope that they can develop a medicine against cancer that is based on TRAIL. The Koreans wondered whether, once that medicine has been developed, hispolon might help the medicine to work better. In-vitro studies have shown that hispolon has a wide range of cancer-inhibiting effects.

The researchers exposed human gut cancer cells to different concentrations of hispolon and TRAIL, and observed that the two substances did indeed reinforce each other's cancer inhibiting effect. Together they activated suicide enzymes such as caspase-8 and 9.

How hispolon helps the immune system to kill cancer cells

How hispolon helps the immune system to kill cancer cells

Hispolon enhanced the production of Death Receptors 4 and 5 in the gut cancer cells, which in turn were activated by TRAIL. It seems that the phenol increases the sensitivity of gut cancer cells to TRAIL in this way.

How hispolon helps the immune system to kill cancer cells

The Koreans repeated their experiments with other kinds of cancer cells and observed that hispolon increased the production of Death Receptors for these too.

"The molecular mechanism of Death Receptor 4 and Death Receptor 5 induction in colon cancer cells was also investigated," the Koreans wrote. "Numerous mechanisms have been suggested for induction of these death receptors, including ROS generation, p53 induction and NF-kB, DNA damage-inducible transcript 3 (DDIT3), peroxisome proliferator-activated receptor and MAPK activation."

"CAAT enhancer binding protein homologous protein [CHOP] is also known to be a regulator of the death receptor via binding of CHOP to the death receptor promoter. We found that CHOP was upregulated by hispolon in HCT-116 cells and that hispolon can induce the death receptor through a CHOP mediated mechanism."

"We also found that hispolon-induced Death Receptor 5 was related to ERK activation, but independent of Jun N-terminal Kinases [JNK]."

"Another mechanism, induction of apoptosis through p53 was also investigated because of the importance of this pathway in the response to cell stress such as chemotherapy and radiotherapy. In this pathway, the upregulation of p53 is essential for an apoptosis event, however, hispolon could not induce p53 in HCT-116 cells."

"Hispolon combined with tumor necrosis factor-related apoptosis-inducing ligand [TRAIL] may be a good candidate for anticancer therapy, however, further studies using animal models are needed to realize this combination anticancer therapy," the researchers conclude.

How hispolon helps the immune system to kill cancer cells

Wild speculation on our part
Might it be that hispolon - and all the other naturally occurring compounds in plant products that activate Death Receptors - enhances the cancer-inhibiting effects of physical exercise too? One effect of physical exercise is that it slows down cancer by inducing immune cells to attack cancer cells.

Oncol Rep. 2016 Feb;35(2):1020-6.

Garlic, prostate cancer and Death Receptor-4 05.11.2014
Protection against bowel cancer, Death Receptors, TRAIL & asparagus 23.04.2014

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