Inhibition of Autophagy Amplifies Baicalein-Induced Apoptosis in Human Colorectal Cancer

Thuy Phan; Vu H Nguyen; Marcela A'lincourt Salazar; Paul Wong; Don J Diamond; John H Yim; Laleh G Melstrom

doi:10.1016/j.omto.2020.08.016

Inhibition of Autophagy Amplifies Baicalein-Induced Apoptosis in Human Colorectal Cancer

Mol Ther Oncolytics. 2020 Aug 29:19:1-7. doi: 10.1016/j.omto.2020.08.016. eCollection 2020 Dec 16.

Authors

Thuy Phan¹, Vu H Nguyen², Marcela A'lincourt Salazar², Paul Wong¹, Don J Diamond², John H Yim¹, Laleh G Melstrom^{1

3}

Affiliations

¹ Department of Surgery, City of Hope Medical Center, Duarte, CA, USA.
² Department of Hematology, City of Hope Medical Center, Duarte, CA, USA.
³ Department of Immuno-Oncology, City of Hope Medical Center, Duarte, CA, USA.

Abstract

Baicalein is a Chinese herbal compound extracted from Scutellaria baicalensis that has anti-tumor properties. The aim of this study was to elucidate the mechanisms of action of baicalein against human colorectal cancer cell lines and to assess whether the anti-proliferative effects of baicalein may be amplified with autophagy inhibition. Human colon cancer cell lines (HT-29, HCT-116, SW480, and SW620) were treated with baicalein alone and in combination with the autophagy inhibitor chloroquine (CQ). Baicalein reduced cell viability in all four colon cancer lines in a dose-dependent fashion. Combination treatment of baicalein and the autophagy inhibitor CQ significantly decreased cell viability compared with baicalein alone in HT-29 and HCT-116 cell lines. Western blot analysis of the HCT-116 cell line treated with both baicalein and CQ demonstrated increased expression of LC3-II, a component of autophagy. The combination of baicalein with CQ culminated in activation of caspase-3-mediated apoptosis. These findings demonstrate that inhibition of autophagy enhanced apoptotic cell death induced by baicalein treatment in colon cancer cell lines. Future work will assess other targetable apoptotic pathways activated by baicalein and autophagy inhibition.

Keywords: apoptosis; autophagy; baicalein; chloroquine; colorectal cancer.