The medical and scientific facts about fenbendazole as possible cancer treatment utility
Fenbendazole destabilizes microtubules of cancer cells by promoting the polymerisation of tubulin. The research suggests that fenbendazole may bind to the tubulin at the same part of the molecule like colchicine does. The effect of fenbendazole on microtubules is milder than that of anticancer agent niclosamide, but more severe than that of Taxol.
Fenbendazole inhibits the development of cancer cells by inhibiting the cell cycle. By still unknown mechanism fenbendazole executed cell cycle arrest in mitotic phase of non-small cell lung cancer cells of A549 strain. Due to this type of cell cycle diversity, cancer cells started to die by apoptosis molecular machinery.
Fenbendazole induced the expression of the most important tumour-suppressor gene p53, as well as activated cyclin-dependent kinase protein p21, which regulates cell cycle. These effects promoted the apoptosis of cancer cells. It is speculated that due to exactly this cell killing mechanism, which is cancer-characteristic (stops the cell cycle of precancerous cells and makes them apoptotic), cancer cells are affected and killed more severely than normal cells (see Fig. 2).
Almost every official microtubule inhibitor chemotherapy, like paclitaxel, docetaxel, vinblastine, vincristine can drive cancer to become chemoresistant. This phenomenon occurs because of the treating cancer with chemotherapy drugs, so cancer develops multiple resistance through alternate gene expression to synthesise machineries to combat these chemotherapies and make them no more effective. The main mechanism of chemoresistance is when cancer cells adapt to excrete the dugs from themselves via special drug efflux pumps called P-glycoproteins. Fenbendazole is not a substrate for P-glycoproteins, so it cannot be excreted out of cancer cells once it gets there. Thus, during the time the tumours and cancer cells does not develop resistance against fenbendazole and it can still kill cancer cells, unlike paclitaxel, docetaxel, vinblastine, vincristine. Other benzimidazole analogues also may have this ability, but it has to be proven scientifically. In parasites, fenbendazole acts not only by inhibiting cell cytoskeleton (functional microtubules) but also is known to be glucose uptake inhibitor (similar to metformin in some cases).
Because of this presumtion, the effect of fenbendazole on glucose uptake and lactate levels was examinated and it was proven that fenbendazole inhibits the uptake consumption of glucose more than 10 times compared to the control treatment (10µM concentration of fenbendazole). Mechanistically this was due to the inhibition of glycolytic pathway enzymes GLUT-4 and Hexokinase II by this anthelmintic drug. The above-discussed protein p53 also controls cancer development by inhibiting the expression and activity of GLUT1 and GLUT4 „glucose gates“of the cell. As expected, the lactate levels were also diminished then compared to control (see Fig. 3). Following experiments showed that fenbendazole acts synergistically with prominent anti-glycolytic molecule DCA (sodium dichloroacetate) and 2-DG (2-deoxyglucose).
Overall in vivo results in mice showed strong anticancer effect of fenbendazole on NSCLC (non-small cell lung cancer) xenografts (tumour implants under the skin, which keep growing as mouse keeps living). The volumes of these tumours after a while were neglible compared to not treated mice (see Fig. 4).
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