Proteasome Inhibitors Induce P53-independent Apoptosis in Human Cancer Cells

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 2011 Jan 13

PMID 21224072

Citations 32

Authors

Bulbul Pandit

Andrei L Gartel

Affiliations

Soon will be listed here.

Abstract

Proteasome inhibitors are used against human cancer, but their mechanisms of action are not entirely understood. For example, the role of the tumor suppressor p53 is controversial. We reevaluated the role of p53 in proteasome inhibitor-induced apoptosis by using isogenic human cancer cell lines with different p53 status. We found that well-known proteasome inhibitors such as MG132 and bortezomib, as well as the recently discovered proteasome inhibitor thiostrepton, induced p53-independent apoptosis in human cancer cell lines that correlated with p53-independent induction of proapoptotic Noxa but not Puma protein. In addition, these drugs inhibited growth of several cancer cell lines independently of p53 status. Notably, thiostrepton induced more potent apoptosis in HepG2 cells with p53 knockdown than in parental cells with wild-type p53. Our data confirm that proteasome inhibitors generally induce p53-independent apoptosis in human cancer cells.

Citing Articles

The Proteasome Inhibitor Bortezomib Induces p53-Dependent Apoptosis in Activated B Cells.

Ochoa T, Rossi A, Woodle E, Hildeman D, Allman D J Immunol. 2023; 212(1):154-164.

PMID: 37966267 PMC: 10872551. DOI: 10.4049/jimmunol.2300212.

Gold Nanoparticles Induced Size Dependent Cytotoxicity on Human Alveolar Adenocarcinoma Cells by Inhibiting the Ubiquitin Proteasome System.

Ibrahim B, Akere T, Chakraborty S, Valsami-Jones E, Ali-Boucetta H Pharmaceutics. 2023; 15(2).

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Proteasome Inhibitors and Their Potential Applicability in Osteosarcoma Treatment.

Van Stiphout C, Luu A, Viloria-Petit A Cancers (Basel). 2022; 14(19).

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Severe cellular stress drives apoptosis through a dual control mechanism independently of p53.

Wang Y, Wang L, Hung T, Hong Y, Chen C, Ho C Cell Death Discov. 2022; 8(1):282.

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The splicing factor DHX38/PRP16 is required for ovarian clear cell carcinoma tumorigenesis, as revealed by a CRISPR-Cas9 screen.

Cona B, Hayashi T, Yamada A, Shimizu N, Yokota N, Nakato R FEBS Open Bio. 2021; 12(3):582-593.

PMID: 34965029 PMC: 8886329. DOI: 10.1002/2211-5463.13358.

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