alkaloid
Alkaloids are a broad class of natural product, naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids.
Alkaloids are produced by a large varie ...
present in the plant '' Chelidonium majus'' (greater celandine). It is a potent, selective, and cell-permeable
protein kinase C
In cell biology, protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and t ...
in vitro
''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...
''. And an efficacious
antagonist
An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.G-protein-coupled CB1 receptors. This molecule also exhibits anticancer qualities and it has served as a base for many potential novel drugs against cancer. Structurally, this molecule has two distinct conformations, one being a positively charged iminium form, and the other being an uncharged form, a pseudo-base.
It is also found in the plants '' Zanthoxylum clava-herculis'' and '' Zanthoxylum rhoifolium'', exhibiting antibacterial activity against ''
Staphylococcus aureus
''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posi ...
'' and other human pathogens.
Research
Antibacterial agent
Chelerythrine is a potent antibacterial agent that has aided in dealing with the emergence of antibacterial resistant bacteria. This molecule has the ability to disrupt a bacteria's cell wall and cell membrane, as well as preventing bacterial growth, all of which contribute to bacterial death.
Cellular apoptosis
Studies have shown that chelerythrine inhibits SERCA activity, more importantly the concentration needed to inhibit this enzyme is within range to that needed to inhibit protein kinase C. The negative regulation of SERCA activity results in accumulation of calcium ions in the cytoplasm, leading to the forced influx of calcium ions to the mitochondria. High calcium ion concentration in the mitochondria greatly alters its normal activity and leads to apoptosis signaling, and eventually cellular destruction. Other cellular transporters, like the
PMCA
The plasma membrane Ca2+ ATPase (PMCA) is a transport protein in the plasma membrane of cell (biology), cells that functions as a calcium pump to remove calcium (Ca2+) from the cell. PMCA function is vital for regulating the amount of Ca2+ with ...
, have also been shown to be negatively regulated by chelerythrine, preventing PMCA to effectively take out calcium ions from inside the cell. This further contributes to the loss of calcium ion balance within the cell and eventual cell death. In triple-negative breast cancer cells, this molecule is found to induce apoptosis. Nuclear fragmentation and chromatin condensation is observed, which is indicative of apoptosis.
Other
Previous studies have showcased chelerythrine's ability to inhibit, or delay, cell proliferation, allowing it to be used to combat cancerous cells and promote cellular apoptosis, both in vivo and in vitro. However, further studies of this alkaloid have revealed that it has low selectivity and it can also promote cellular apoptosis of non-cancerous cells, thus displaying cytotoxic behavior. The creation of chelerythrine analogs have helped exploit this molecule's anticancer capabilities, while lessening its cytotoxic effects on non-cancerous cells. These novel analogs have been modified to have increased specificity for cancerous cells, thus decreasing cytotoxic effects and non-cancerous cell apoptosis.
Anti-cancer mechanisms
Depending on the form of cancer, chelerythrine can exhibit different effects on tumor cells, leading to inhibition of tumor growth. These mechanisms include inducing apoptosis, arrest of the cell cycle, promoting autophagy of cancerous cells, and the inhibition of telomerase. It has been found to be a possible anti-cancer agent for liver, gastric, breast, renal, and cervical cancers. Despite these claims, it is important to note that the related compound sanguinarine is associated with severe adverse effects. This is insufficient evidence to endorse the usage of chelerythrine present in botanical products as a cancer treatment.
Role as a protein kinase C inhibitor
Studies show that chelerythrine is a specific and potent
protein kinase C
In cell biology, protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and t ...
inhibitor. Due to its inhibitory effects on protein kinase C, it has been found of use against triple-negative breast cancer. By inhibiting protein kinase C, signaling pathways are disrupted, inducing cell cycle arrest.