Thymoquinone Promotes Pancreatic Cancer Cell Death and Reduction of Tumor Size through Combined Inhibition of Histone Deacetylation and Induction of Histone Acetylation

Relles, Daniel and Chipitsyna, Galina I. and Gong, Qiaoke and Yeo, Charles J. and Arafat, Hwyda A. (2016) Thymoquinone Promotes Pancreatic Cancer Cell Death and Reduction of Tumor Size through Combined Inhibition of Histone Deacetylation and Induction of Histone Acetylation. Advances in Preventive Medicine, 2016. pp. 1-9. ISSN 2090-3480

[thumbnail of 1407840.pdf] Text
1407840.pdf - Published Version

Download (3MB)

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is virtually therapy-resistant. As noninvasive lesions progress to malignancy, the precursor period provides a window for cancer therapies that can interfere with neoplastic progression. Thymoquinone (Tq), a major bioactive component of essential oil from Nigella sativa’s seeds, has demonstrated antineoplastic activities in multiple cancers. In this study, we investigated antineoplastic potential of Tq in human PDAC cell lines, AsPC-1 and MiaPaCa-2. Tq (10–50 μM) inhibited cell viability and proliferation and caused partial G2 cycle arrest in dose-dependent manner in both cell lines. Cells accumulated in subG0/G1 phase, indicating apoptosis. This was associated with upregulation of p53 and downregulation of Bcl-2. Independently of p53, Tq increased p21 mRNA expression 12-fold. Tq also induced H4 acetylation (lysine 12) and downregulated HDACs activity, reducing expression of HDACs 1, 2, and 3 by 40–60%. In vivo, Tq significantly reduced tumor size in 67% of established tumor xenografts (), along with increased H4 acetylation and reduced HDACs expression. Our results showed that Tq mediated posttranslational modification of histone acetylation, inhibited HDACs expression, and induced proapoptotic signaling pathways. These molecular targets demonstrate rationale for using Tq as a promising antineoplastic agent to prevent postoperative cancer recurrence and to prolong survival of PDAC patients after surgical resection.

Item Type: Article
Subjects: Universal Eprints > Medical Science
Depositing User: Managing Editor
Date Deposited: 28 Nov 2022 06:27
Last Modified: 29 May 2024 05:12
URI: http://journal.article2publish.com/id/eprint/482

Actions (login required)

View Item
View Item