Medicinal plants have long been used to treat illness. A recent article published in the June 2018 journal Molecules has outlined the biological antiproliferative tumor mechanism of an isolated terpenoid from the Peruvian medicinal plant Plagiochila disticha. This seaweed like plant thrives in the rainforest but harbors a specific molecule with potential for cancer research.
The apoptotic effects of this molecule on tumor cells was reportedly found through an investigational ethnobotanical study in the 1990’s, as part of a large project examining the properties of medicinal plants of the Aguarana tribe in Peru. Plagiochila disticha is a liverwort species; plagiochiline A was the special molecule found to directly inhibit the growth of tumor cells in multiple different solid tumor types, however the mechanism of action was unknown.
This recent study sought to explore the molecular mechanism and cellular action as part of plagiochiline A’s antiproliferative properties. The authors evaluated the distribution of cells during each phase of mitosis in the presence of plagiochiline A because many plant-derived molecules that are anti-tumor act through cell cycle arrest mechanisms.
The researchers found that plagiochiline A acts in a unique way, different from other cytotoxic medicines like vinblastine and vincristine or paclitaxel and docetaxel. The former bind to microtubule ends and disrupt the movement of chromosomes to the metaphase plate during prometaphase. The latter block mitosis through disassembly of the microtubules prior to spindle formation. Plagiochiline A affects cytokinesis at the stage where the plasma membrane reforms and pinches off to result in two identical cells. Plagiochiline A blocks the formation of endosomal sorting complexes which act to constrict the plasma membrane to form those two separate identical cells. This is normally a tightly regulated cellular process in order to catch any cells that have errantly or incorrectly replicated and not properly divided. There is a division checkpoint, or abscission checkpoint, which is activated when there are chromosomal separation errors. Interestingly, visualization of cells inihibited by plagiochiline A do not exhibit the typical morphological characterizations associated with mitotic cytokinetic disruptions including multinucleated cells, increased chromatin condensation, and presence of mitotic spindle apparatuses.
There are very few known agents that successfully target cytokinesis and fewer still that disrupt the cycle at the abscission stage without disrupting other mitotic processes. There is value in utilizing this compound because there is growing support for this as a viable cancer treatment target.
Sources: Molecules, Planta Medica,
