Promises from an Almost Extinct Tree

https://pixabay.com/photos/weeping-willow-willow-tree-branch-3089113/

https://pixabay.com/photos/weeping-willow-willow-tree-branch-3089113/

Throughout history, many advancements in various types of medical drugs have originated from plants. Aspirin, commonly used as a pain reliever, was derived from salicin, a compound in the bark of white willow trees (1). Use of these willow barks dates back to 400 BC, “when people were advised to chew on the bark to reduce fever and inflammation” (1). Artemisinin, “a powerful ingredient extracted from Artemisia annua” is another plant-derived compound that was used to create modern antimalarial drugs” (2).

Potential for a revolutionary plant-derived cancer medicine is also being studied. This could affect millions of cancer cases across the globe. According to the CDC, the number of new cancer cases is projected to be 1.9 million per year in 2020, while the rate of people who die from cancer is projected to drop from 171 deaths per 100,000 people (from 2010 statistics) to 151 deaths per 100,000 in 2020 (3). A new potential therapeutic cancer drug may have been inspired by a compound found in Abies beshanzuensis, an endangered tree found in Southeast China. Only three of these trees, their existence in a critical state, are left in a reserve in southeastern China (4).

The plant was originally being studied by chemists in China to find treatment for diabetes. The study seemed to be fruitless until Mingji Dai, an organic chemist at Purdue University, found evidence that suggested the plant’s therapeutic potential for cancer (5).

From the tree, they extracted some molecules called Abiespiroside A, beshanzuenone C, and beshuanzuenone D sesquiterpenoids from the plant (5). The research team found that these sesquiterpenoids “demonstrated weak inhibiting activity against protein tyrosine phosphatase 1B (PTP1B)” (6).There has been mounting evidence that a certain protein tyrosine phosphatase (PTP) called SHP2 is associated a wide variety of cancers and “cancer-related processes, including cancer cell invasion and metastasis, apoptosis, DNA damage, cell proliferation, cell cycle and drug resistance (7). Therefore, the PTP inhibiting mechanisms in the sesquiterpenoids suppress SHP2 cellular activities involved in proliferation.

Many drug companies have been trying to make inhibitors for SHP2. However because of the highly conserved and polar nature of the catalytic sites of protein tyrosine phosphatases (PTP), it is very challenging to develop PTP inhibitors (8). Working with Zhong-Yin Zhang, a professor of medicinal chemistry at Purdue University, Dai and the team manufactured “compound 30,” which is an analog of one of the compounds in the tree (5). SHP2-targeted cancer treatment and therapies may regulate the growth of cancer cells and diminish oncogenic properties.

So what are the functional consequences of the synthesized compounds? The primary goal of compound 30 is to make a stable, covalent bond with SHP2, blocking “substrate access, therefore, resulting in suppressed PTP activity” (8). Dai and his team also created compound 29 which was used as a “bait” inside cells to “catch” an enzyme called POLE3 which is used to synthesize and repair DNA (5).

Dai says that the potential of Compound 29 lies in the interactions with common cancer drugs which could lead to improvements in these drugs telling us “something new about the function of POLE3” (9). Understanding the involvement of POLE3 could reverse DNA damages done by the toxic cancer drugs and using SHP2 inhibitors with strong bonds could lead to prevention of cell proliferation and localize the tumor effectively. This endangered Chinese fir tree holds promise for development of a more effective and therapeutic cancer treatment.

Edited by: Jessika Baral




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