Bafilomycin A1 and its attenuating effect on tumour growth in systemic malignancies, especially gastrointestinal malignancies

The paper by Wang et al. [1] published in Clinical Science provided for highly interesting reading. Interestingly, recent data confirms that bafilomycin A1 decreases tumour growth in a number of systemic malignancies. For instance, it decreases growth in colonic malignancies. It mediates its antineoplastic effects by attenuating lysosomal acidification within the cancerous cells. At the same time, p38 phosphorylation is markedly attenuated [2] and mitochondrial uncoupling is typically augmented. On the other hand, caspase 7 and caspase 8 cleavage is accentuated. As a result, macro-autophagy is markedly inhibited, resulting in G₀/G₁-phase arrest. Bafilomycin A1 administration also has a negative impact on HIF-1α (hypoxia-inducible factor-1α) cleavage [3] and subsequent accentuation of HIF-1α levels. This results in p21 induction and consequent cell-cycle arrest. JNK (c-Jun N-terminal kinase) phosphorylation is also decreased significantly, whereas p21 is typically up-regulated. The ultimate result is augmented...