DpdtbA-Induced Growth Inhibition in Human Esophageal Cancer Cells Involved Inactivation of the p53EGFRAKT Pathway

Joint Authors

Li, Changzheng
Li, Yongli
Li, Cuiping
Wang, Zhuo
Guo, Xingshuang
Yan, Zhaoyu
Gao, Fulian

Source

Oxidative Medicine and Cellular Longevity

Issue

Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-14, 14 p.

Publisher

Hindawi Publishing Corporation

Publication Date

2019-07-01

Country of Publication

Egypt

No. of Pages

14

Main Subjects

Biology

Abstract EN

Esophageal cancer (ESC) is one of the most deadly diseases for human.

p53 in most cancers, including ESC cell, is mutated, and the mutated p53 losses its original function and acquires “gain of function” that allows for promoting the hallmarks of cancer, such as antiapoptosis, metastasis, invasion, angiogenesis, and resistance to chemotherapy.

Targeting p53 through either introducing wild-type or degrading mutated p53 is an important strategy in cancer therapy.

Di-2,2′-pyridine ketone dithiocarbamate s-butyric acid (DpdtbA) has significant growth inhibition against gastric cancer lines in previous study.

Similar action in ESC cell lines but a novel molecular mechanism was observed in the present study.

The results showed that DpdtbA exhibited an excellent antiproliferative effect for ESC cell lines (IC50≤4.5±0.4 μM for Kyse 450, 3.2±0.6 μM for Kyse 510 cell, and 10.0±0.6 μM for Kyse 150) and led to cell cycle arrest at the S phase which correlated to CDK2 downregulation.

The mechanistic study suggested that growth inhibition was related to ROS-mediated apoptosis, and ROS production was due to SOD inhibition initiated by DpdtbA rather than occurrence of ferritinophagy.

In addition, DpdtbA also induced a downregulation of EGFR, p53, and AKT, which hinted that mutant p53 still played a role in the regulation of its downstream targets.

Further study revealed that the downregulation of p53 was through stub1- (chip-) mediated autophagic degradation rather than MDM2-mediated ubiquitination.

Taken together, the DpdtbA-induced growth inhibition in a mechanism was through inactivating the p53/EGFR/AKT signal pathway.

American Psychological Association (APA)

Wang, Zhuo& Li, Cuiping& Li, Yongli& Guo, Xingshuang& Yan, Zhaoyu& Gao, Fulian…[et al.]. 2019. DpdtbA-Induced Growth Inhibition in Human Esophageal Cancer Cells Involved Inactivation of the p53EGFRAKT Pathway. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-14.
https://search.emarefa.net/detail/BIM-1204134

Modern Language Association (MLA)

Wang, Zhuo…[et al.]. DpdtbA-Induced Growth Inhibition in Human Esophageal Cancer Cells Involved Inactivation of the p53EGFRAKT Pathway. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-14.
https://search.emarefa.net/detail/BIM-1204134

American Medical Association (AMA)

Wang, Zhuo& Li, Cuiping& Li, Yongli& Guo, Xingshuang& Yan, Zhaoyu& Gao, Fulian…[et al.]. DpdtbA-Induced Growth Inhibition in Human Esophageal Cancer Cells Involved Inactivation of the p53EGFRAKT Pathway. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-14.
https://search.emarefa.net/detail/BIM-1204134

Data Type

Journal Articles

Language

English

Notes

Includes bibliographical references

Record ID

BIM-1204134