Cancer Stem Cells: Breakthrough Research

Cancer stem cells (CSCs) are a type of stem cell specific to cancer, that is able to reproduce through self-renewal and regeneration into new tumor cells. Cancer stem cells are most dangerous as they are resistant to chemotherapy and cause relapse by creating new tumors. It is critical to find treatments for cancer stem cells to prevent this disease from resurfacing in a person again and again.

Cancer is an Extremely Difficult Disease because it is so Difficult to Eradicate.

Cancer diagnosis is followed by treatments such as chemotherapy, radiation therapy and surgery. These treatments can be successful in completely abolishing cancer, but it is common for the treatments to kill cancer cells and to shrink tumors and lead to a remission rather than a cure. Remission is a relief from aggressive tumor growth but it is not a cure because some cancer cells—perhaps only a small number—have survived the treatment and though they may be quiescent they are still in the body and can rekindle, spread, and form new tumors. This is the dreaded process of cancer recurrence that often follows a remission that itself may last for months or even years. So if the cancer is not completely eradicated by therapy it remains and the stage is set for recurrence. Another round of cancer treatments may lead to another remission followed by another recurrence and the cycle repeats usually with shorter remissions and more aggressive recurrences. Just why does this happen? Why can't the cancer be completely abolished? What process enables the cancer to come back?

Why Recurrences Happen?

The answers to these questions are now coming in to view. First, we know that some of the cancer cells survive treatment which means they have become resistant to the anti-cancer drug or drugs being used. In addition to drug resistance we also know that the cells that survive treatments have the capacity to spread out from the original site of the cancer to other parts of the body. And we also know that that at these new sites these survivors can initiate new tumor growth. So cancer recurrence is triggered by specialized cancer cells that are drug resistant, metastatic and tumorigenic. These specialized cells form a subpopulation of the cells in a tumor distinct from the primary cancer cells— the ones that are susceptible to anti-cancer drugs. These specialized cells, defined by these three properties, are now referred to as cancer stem cells (CSCs). This name is used because cancer stem cells resemble healthy stem cells in their capacity for endurance and self-renewal. Indeed, in generating stem cells, the tumor hijacks the characteristics of normal stem cells and thereby enables its own self renewal which accounts for cancer recurrence. Healthy stem cells normally enable repair and regeneration of tissues and organs whereas cancer stem cells enable persistence of the disease and generation of new tumors.

A new generation of cancer therapies are needed to target cancer stem cells as well as primary tumor cells. By removing cancer stem cells these new therapies will remove the mechanism for cancer recurrence and thereby make possible complete eradication of cancer and true cancer cures. So far, very few agents have shown activity against cancer stem cells. Two new studies have shown that the Pao pereira and Rauwolfia vomitoria plant extracts are active against pancreatic cancer stem cells.

Research by Kansas University Medical Center

Many studies have shown that the Pao pereira and Rauwolfia vomitoria extracts are active against a broad spectrum of cancers. In two earlier publications Dr. Qi Chen's group at Kansas University Medical Center showed that these two plant extracts are active against pancreatic cancer cells in both cell based and animal experiments. In light of the critical importance of cancer stem cells in cancer progression, The Beljanski Foundation asked Dr. Chen to test the activity of the extracts against pancreatic cancer stem cells.

2 Plant Extracts Treating Cancer Stem Cells

This new research has shown that the Pao pereira and Rauwolfia vomitoria extracts are indeed active against pancreatic cancer stem cells. Cancer stem cells (CSCs) can be identified in vitro as clusters of cells called spheroids. Both extracts were shown to completely abolish these spheroids. Cancer stem cells can also be identified by cell surface markers that may be used to distinguish them from primary cancer cells. Both Pao pereira and Rauwolfia vomitoria extracts were shown to significantly reduce the pancreatic CSC population identified using specific cell surface markers.

CSCs are also defined by their capacity to form tumors in vivo. To be effective, an anti-CSC agent must reduce the rate of tumor formation. Both extracts passed this critical test, significantly inhibiting the tumorigenicity of pancreatic CSCs.

The extracts induce apoptosis in primary ovarian and pancreatic cancer cells, but they act through a different mechanism of action in cancer stem cells. The new experiments demonstrate that the extracts suppress the Wnt/β-catenin signaling pathway. When this pathway is activated, β-catenin transcriptional factor accumulates in the nucleus and up regulates genes that promote CSC 'stemness', including self-renewal and drug resistance. The extracts target this pathway, reducing the level beta-catenin in the nucleus, and thereby reducing CSC activity.

Pao Pereira Inhibits Cancer Stem Cells

In vitro experiments show Pao pereira reducing the number of pancreatic CSCs (see figure below).Cancer Stem Cells and Pao Periera in vitro

As the amount of Pao pereira is increased, the number of pancreatic cancer stem cells (spheroids) decrease dramatically. In additional cell-based studies, the Pao pereira extract also specifically reduced the pancreatic cancer stem cell population.

In vivo experiments showed that Pao pereira inhibited the capacity of pancreatic CSCs to form tumors – the defining characteristic of CSCs – and significantly reduce the volume of tumors that did form (see figure below).

Cancer Stem Cells and Pao Pereria in vivo

At day 6 (Figure A), tumor formation rate in the control group reached 80%, while in Pao-treated group it was only 10%. At day 20, when the treatment stopped, all mice in control group were bearing tumors on both flanks (100% tumor formation), while the Pao-treated group only had 30% tumor formation. Growth of the formed tumors was also inhibited by Pao pereira treatment compared with the control group (Figure B). A long-term inhibitory effect in tumor growth was observed after treatment had stopped. Pao pereira works by lowering the signals that trigger the pancreatic cancer stem-like cell properties that lead to cancer recurrence.

The researchers at Kansas University Medical Center concluded that Pao pereira holds great promise as a novel treatment for targeting pancreatic CSCs, an essential component of treatments that will lead to real cancer cures.

Click below read the full publication:
Extract of the Medicinal Plant Pao Pereira Inhibits Pancreatic Cancer Stem-Like Cell In Vitro and In Vivo
Dong, P. Chen and Q Chen. Integrative Cancer Therapies. July 2018. doi: 10.1177/1534735418786027

Rauwolfia Vomitoria Active Against Cancer Stem Cells

In vitro experiments show Rauwolfia vomitoria reducing the number of pancreatic CSCs in a variety of cell lines (see figure below).

Cancer Stem Cells and Rauwolfia Vomitoria in vitro

As the amount of Rauwolfia vomitoria is increased, the number of pancreatic cancer stem cells drastically decreases.

Even more impressive, the in vivo data demonstrates that Rauwolfia counteracts the defining behavior of CSCs, their ability to promote formation and growth of new pancreatic tumors. The charts below show how the single Rauwolfia treatment significantly inhibited the tumor formation rate (C) and the size of formed tumors (D).

Cancer Stem Cells and Rauwolfia Vomitoria in vivo

The researchers at Kansas University Medical Center concluded that, much like Pao pereria, Rauwolfia vomitoria also holds great promise as a novel treatment for targeting pancreatic CSCs. The two natural extracts are a vital method of treatments that are bringing new, real cancer cures.

Click below read the full publication:
Inhibition of Pancreatic Cancer Stem Cells by Rauwolfia vomitoria extract.
Dong, P. Chen and Q Chen. Oncology Reports. September 2018.
doi: 10.3892/or.2018.6713

Pao Pereria and Rauwolfia Vomitoria Extracts Treat Cancer Stem Cells

The data showing how both Pao pereria and Rauwolfia vomitoria extracts treat cancer stem cells is music to the ears of more than 32,000 cancer patients. That’s the number of estimated pancreatic cancer cases diagnosed annually and until now, less than 5% survived beyond five years. This new breakthrough spotlighting the extract’s effect on CSCs is the new game changer for not only patients, but also the oncologists caring for those patients.

In light of their broad spectrum anti-cancer activity, Pao pereria and Rauwolfia vomitoria are expected to be effective against stem cells of many kinds of cancer in both men and women.