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Bafilomycin A1 is a macrolide antibiotic isolated from Streptomyces species. Baf-A1 is an autophagy inhibitor, cell growth inhibitor and apoptosis inducer. Up until 2016 there have been several papers and studies that provide evidence that Baf-A1 is an autophagy inhibitor that prevents cancer cell proliferation and tumor regrowth in different cancer cell lines such as gastric cancer cell lines, pediatric leukemia cell lines and other tumor models. But a very recent paper published in Feb 2017 by Polish scientists gives a different view of Baf-A1’s effects on colon cancer cells.
This latest study is centered on poor prognosis of colon cancer, and increased relapse rate after cessation of chemotherapy. The relapse is attributed to the Senescent Cancer Cells (cells that have stopped replicating or have reached their maximum count of replication cycle). It has been shown that chemotherapy induces senescence in cancer cells which is called Therapy Induced Senescence – TIS. Some of these senescent cancer cells transiently display stem cell like properties such as tumorigenesis and tumor regrowth properties. Some Cancer Stem Cells (CSC’s) are quiescent or undergo slow cycling phase and hence, escape the therapeutic intervention which has been pointed out as the possible cause for tumor relapse.
Since senescent cells lack the ability to replicate, they require autophagy to eliminate the damaged organelles, proteins or aggregates. Autophagy is the mechanism which helps these cells to survive and is crucial in maintaining their stem cell features. Hence it is possible to prevent the senescent cells from re-populating and forming tumor if autophagy is inhibited. As mentioned above, earlier research has shown that Baf-A1 was responsible for inhibiting autophagy in cancer cells and induced apoptosis. Based on this evidence the polish researchers used HCT116 cells – human colon cancer cells and repeatedly treated them with a chemotherapeutic drug, Doxorubicin. Eventually after withdrawing the drug, the cancer cells developed senescence and displayed stem cell like characteristics.
After discontinuing the chemotherapy the Senescent Cancer Cells were treated with a single dose of Baf-A1. Baf-A1 is an autophagy inhibitor, it prevents the fusion between auto phagosomes and lysosomes. Initially Baf-A1 inhibited autophagy but later on it reactivated their tumor forming capabilities, therefore questioning the ability of Baf-A1 to inhibit autophagy and cause apoptosis in senescent cancer cells.
In conclusion scientists believe that more studies and research is required to establish Baf-A1 as a promising candidate for cancer therapy and to further understand the mechanism of cancer maintenance and regrowth in senescent cancer cells.
Bafilomycin A1 triggers proliferative potential of senescent cancer cells in vitro and in NOD/SCID mice – Halina Was, Kamila Barszcz, Joanna Czarnecka, Agata Kowalczyk, Tytus Bernas, Ewelina Uzarowska, Paulina Koza, Agata Klejman, Katarzyna Piwocka, Bozena Kaminska, and Eva Sikora
Inhibition of autophagy by bafilomycin A1 promotes chemosensitivity of gastric cancer cells – Li, Liang-qing; Xie, Wen-jun; Pan, Dun; Chen, Hui; Zhang, Lin.