Multiple myeloma (MM) is the second most occurring cancer in the hematologic system (blood, spleen, bone marrow and the liver) after non-Hodgkin lymphoma. Multiple myeloma is a cancer that forms in a type of white blood cell called a plasma cell. Plasma cells fight infections by making antibodies that recognize and attack germs. Multiple Myeloma causes cancer cells to accumulate in the bone marrow, where they crowd out healthy blood cells. Existing therapies are bortezomib, thalidomide and lenalidomide that enhance remission rates and prolong survival. It is still regarded as incurable due to the common development of drug resistance and therapeutic complications.
Pterostilbene has been reported to have anti-oxidant, anti-inflammatory, cardiovascular protective and anti-tumor effects. The anti-cancer reported are for example lung, breast and prostate cancer. It is a dimethylated analog of the well known resveratrol but with better bioavailability and longer half-life. Resveratrol research has found that it can inhibit the proliferation of human MM cell lines and alter the population of S phase. Resveratrol is also found to enhance the apoptotic effect of bortezomib and thalidomide, thus overcoming the chemoresistance of MM. Together this motivated a research team, comprised out of scientists from renowed chinese institutes, to examine the anti-cancer potential of pterostilbene against MM. Both in-vitro and in-vivo experiments were carried out.
In the first in-vitro experiment cell proliferation was measured for various MM cell lines H929, ARP-1, OCI-MY5 and RPMI-8226 while being treated with incremental doses of pterostilbene (10, 20, 30, 40 and 50 μM) for 24, 48 and 72 h. Cell proliferation is the process that results in an increase of the number of cells, it is defined by the balance between cell divisions and cell loss through cell death or differentiation. Cell proliferation is increased in tumors. Administration of pterostilbene resulted in inhibition of proliferation with the best results at the highest doses. In the figure above you can see the results of the various doses after 48 hours.
In the second in-vitro experiment the impact of pterostilbene on apoptosis (cell death) was studied for the H929 cell line (unfortunately the researchers did not do this experiment for all cell lines). Given the inhibition observed in the first in-vitro experiement an increase in apoptosis as result of the pterostilbene treatment would be logical. As expected apoptosis increased in a time- and dose-dependent manner. Compared to the control group (6.36% ± 0.61%), apoptosis was increased at 48h in the 10 μM dose with 14.09% ± 0.61%, for the 20 μM dose with 22.91% ± 2.84% and for the 40 μM with 54.87% ± 2.85%. At the longer 72 hours the increase in apoptosis for the 40 μM dose group was 71.02% ± 1.95%.
Further analyses led the researchers to conclude that apoptosis increased because of higher levels of cleaved caspase-3, cleaved caspase-8 and cleaved caspase-9, indicating that pterostilbene may induce both the extrinsic and intrinsic apoptotic pathway. This conclusion was strengthened by a test in which a pan-caspase inhibitor blocked the apoptosis of H929 cells that were treated with pterostilbene. Further analyses demonstrated that treatment resulted in loss of mitochondrial membrane potential (32.34% ± 2.22%) compared with the control group (11.61% ± 1.11%). It was also shown that pterostilbene enhanced the activation of phosphorylated extracellular regulated protein kinases (ERK) 1/2 and c-Jun N-terminal kinase as part of the induced apoptosis
In normal blood cells (PBMCs) no effect of the treatment was observed, suggesting that pterostilbene may be a safe substance for treatment of MM.
For the in-vivo test H929 cells were subcutaneously implanted into the flank of four-week-old female non-obese diabetes/severe immunodeficiency (NOD/SCID) mice and injected with control substance or pterostilbene at 50 mg/kg for 14 days.
As can be seen from the figure on the left the administration of pterostilbene resulted in a significant decrease in tumor volume.
All together, the results of this study indicate that pterostilbene has a clear anti-tumor effect on Multiple Myeloma cells and may provide a new therapeutic option for patients. Unfortunately the mice in the in-vivo experiment were injected with pterostilbene so a direct dosing analyses is not possible.
Taking the good bio-availability and long half life into account the results strenghtens the case of pterostilbene being taken as part of a cancer preventative supplementation stack. The author of the article takes it on daily basis. You can find the study here.