Dataset Information

Chloroquine augments TRAIL-induced apoptosis and induces G2/M phase arrest in human pancreatic cancer cells.

ABSTRACT: Autophagy contributes to the treatment-resistance of many types of cancers, and chloroquine (CQ) inhibits autophagy. The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) kills cancer cells but is minimally cytotoxic to normal cells. However, because the therapeutic efficacy of TRAIL is limited, it is necessary to augment TRAIL-induced anti-tumor effects. In this study, we explored the anti-tumor effects of a combination of CQ and TRAIL on two human pancreatic cancer cell lines: TRAIL-sensitive MiaPaCa-2 cells and Panc-1 cells that are less sensitive to TRAIL. Although both CQ and TRAIL reduced cancer cell viability in a dose-dependent manner, the combination acted synergistically. CQ increased the expression level of type-II LC3B without decreasing the expression of p62, an autophagic substrate, thus indicating inhibition of autophagy. CQ did not increase the levels of death receptors on cancer cells but reduced the expression of anti-apoptotic proteins. A combination of CQ and TRAIL significantly increased cancer cell apoptosis. CQ induced cell-cycle arrest in the G2/M phase. Also, CQ increased the p21 level but reduced that of cyclin B1. A combination of CQ and TRAIL reduced the colony-forming abilities of cancer cells to extents greater than either material alone. In xenograft models, combination CQ and TRAIL therapy significantly suppressed the growth of subcutaneously established MiaPaCa-2 and Panc-1 cells, compared with the untreated or monotherapy groups. Together, the results indicate that CQ in combination with TRAIL may be useful to treat human pancreatic cancer.

SUBMITTER: Monma H

PROVIDER: S-EPMC5841811 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Chloroquine augments TRAIL-induced apoptosis and induces G2/M phase arrest in human pancreatic cancer cells.

Monma Hiroyuki H Iida Yuichi Y Moritani Tamami T Okimoto Tamio T Tanino Ryosuke R Tajima Yoshitsugu Y Harada Mamoru M

PloS one 20180307 3

Autophagy contributes to the treatment-resistance of many types of cancers, and chloroquine (CQ) inhibits autophagy. The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) kills cancer cells but is minimally cytotoxic to normal cells. However, because the therapeutic efficacy of TRAIL is limited, it is necessary to augment TRAIL-induced anti-tumor effects. In this study, we explored the anti-tumor effects of a combination of CQ and TRAIL on two human pancreatic cancer cell lin ...[more]

PMID: 29513749

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Dataset Information

Chloroquine augments TRAIL-induced apoptosis and induces G2/M phase arrest in human pancreatic cancer cells.

Publications

Chloroquine augments TRAIL-induced apoptosis and induces G2/M phase arrest in human pancreatic cancer cells.

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