Background: Autophagy is a catabolic process that has a vital role in cancer progression and treatment. Current
chemotherapeutic agents, which target autophagy, result in growth inhibition in many cancer types. In this study, we examined
the role of autophagy in breast cancer (BCa) patients as well as BCa cell lines.
Methods: Tissue microarray was used to detect the expression of an autophagy marker, LC3B in BCa patients (normal/
hyperplasia ¼ 8; grade-I ¼ 15, grade-II ¼ 84, and grade-III ¼ 27) and BCa cell lines. To modulate the activation of autophagy, we
used novel herbal compound nimocinol acetate (NA) in BCa cell lines and the anticancer activity was measured by phenotypic and
Results: LC3B is highly expressed in tumours as compared with normal tissues. Activation of LC3B in NA-treated BCa (MCF-7 and
MDA-MB-231) cells was evident as compared with other autophagy makers. Further, our results confirmed that NAtranscriptionally
regulates LC3B (as confirmed by mRNA levels and reporter assay), which resulted in the formation of acidic
autophagy vesicles and autolysosomes in BCa cells. Nimocinol acetate inhibited mTOR-mediated pro-survival signalling that
resulted in inhibition of growth in BCa cells without affecting normal breast epithelial cells. Downregulation of LC3B expression by
siRNA significantly inhibited the anticancer effects of NA in BCa cells.
Conclusions: Together, our results suggest that LC3B is highly expressed in BCa tissues and increasing the threshold of LC3B
activation dictates the pro-apoptotic function, which in turn, suppresses the growth of BCa cells. Nimocinol acetate could be a
potential agent for treatment of BCa.