Imperial College London


Faculty of MedicineDepartment of Surgery & Cancer




+44 (0)20 3313 3759eric.aboagye




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BibTex format

author = {Kaliszczak, M and Hechanova, E and Alsadah, H and Li, M and Parzych, K and Auner, H and Aboagye, EO},
doi = {10.1038/s41416-018-0232-5},
journal = {British Journal of Cancer},
pages = {1278--1287},
title = {The HDAC6 inhibitor C1A modulates autophagy substrates in diverse cancer cells and induces cell death},
url = {},
volume = {119},
year = {2018}

RIS format (EndNote, RefMan)

AB - BACKGROUND: Cytosolic Deacetylase HDAC6 is involved in the autophagy degradationpathway of malformed proteins, an important survival mechanism in cancer cells. Weevaluated modulation of autophagy-related proteins and cell death by the HDAC6-selectiveinhibitor C1A.METHODS: Autophagy substrates (LC3 and p62 proteins) and endoplasmic reticulum (ER)stress phenotype were determined. Caspase 3/7 activation and cellular proliferation assayswere used to assess consequences of autophagy modulation.RESULTS: C1A potently resolved autophagy substrates induced by 3-MA and chloroquine.The mechanism of autophagy inhibition by HDAC6 genetic knockout or C1A treatmentwas consistent with abrogation of autophagosome-lysosome fusion, and decrease of Mycprotein. C1A alone or combined with the proteasome inhibitor, bortezomib, enhanced celldeath in malignant cells demonstrating the complementary roles of the proteasome andautophagy pathways for clearing malformed proteins. Myc positive neuroblastoma, KRASpositive colorectal cancer and multiple myeloma cells showed marked cell growthinhibition in response to HDAC6 inhibitors. Finally, growth of neuroblastoma xenograftswas arrested in vivo by single agent C1A, while combination with bortezomib slowed thegrowth of colorectal cancer xenografts.CONCLUSIONS: C1A resolves autophagy substrates in malignant cells and induces celldeath, warranting its use for in vivo pre-clinical autophagy research.
AU - Kaliszczak,M
AU - Hechanova,E
AU - Alsadah,H
AU - Li,M
AU - Parzych,K
AU - Auner,H
AU - Aboagye,EO
DO - 10.1038/s41416-018-0232-5
EP - 1287
PY - 2018///
SN - 0007-0920
SP - 1278
TI - The HDAC6 inhibitor C1A modulates autophagy substrates in diverse cancer cells and induces cell death
T2 - British Journal of Cancer
UR -
UR -
VL - 119
ER -