There are several biological actions of betulinic acid, that it might induce when threating various deseases. As it is know, betulinic acid shows activity against cancer, HIV, shows anti-inflammatory properties, etc. Moreover, each of these diseases has its own biological pathway that betulinic acid induces. Therefore, researchers are still focused on finding them as not all of them are fully known.
As we mentioned, research concludes that betulinic acid is effective against cancer. However, scientists are still unsure about how biological actions of betulinic acid takes place and real node of action. Currently, researchers believe that betulinic acid exerts its effects through pathways like:
- induction of apoptosis
- regulation of autophagy machinery
- inhibition of angiogenesis and metastasis
- chemo-sensitization mechanisms
Programmed cell death – apoptosis is a cellular mechanism which plays important part of physiological and pathological conditions. Literature shows, that apotosis is one of the major pathways for anticancer properties associated to betulinic acid. Research shows, that treating isolated mitochondria with betulinic acid leads to loss of mitochondrial membrane potential. Furthermore, this indudeces apoptosis by disrupting mitochondrial permeability.
Betulinic acid has considerable potential to regulate expression levels of proteins from BLC-2 family as well. It is know, that these proteins regulates cell death by inhibiting or inducing apoptosis.
Decomposition of fatty acids in mitochondrial outer layer is another way that leads to apotosis. By inhibiting expression of Seroyl-CoA-desatrase (SCD-1), enzyme that is important for cell de novo fatty acid synthesis, is another way betulinic acid induces cell apoptosis.
Autophagy is process that regulates degradation and reuse of damaged proteins and organelles in stress conditions. If this process is over-induces, it might induce another way of cell death (type II programmed cell death). Semi-synthetic glycosylated derivatives of betulinic acid has shown induction of this process by destabilization of lysosomes. PI3K-AKT-mTOR signaling pathway inhibition of betulinic acid results in protective autophagy in colorectal cancer cells and leads to cell death as well.
Inhibition of angiogenesis and metastasis
Angiogenesis and metastasis are mechanisms that aggregates progression and growth of cancer. Therefore, there are several cellular processes in these mechanisms. Matrix metalloproteinases, a group of calcium dependent zinc containing proteins are proteins that control these processes. It is possible to inhibit angiogeneses by inhibition of genes that expresses these proteins (HIF-1a and VEGF) with betulinic acid in endometrical cancer cells.
Moreover, there are evidence that shows, that betulinic acid significantly inhibits migration and invasion of cancer cells. It does so by:
- downregulating metalloproteinases MMP2 and MMP9
- upregulating tissues to inhibit use of MMP2
It is clear, that there are overwhelming nodes of action, that this molecule can induce. And thanks to this, there is still a far way ahead of us to research.