Triptolide inhibits Wnt signaling in NSCLC through upregulation of multiple Wnt inhibitory factors via epigenetic modifications to Histone H3.

International Journal of Cancer. Journal International Du Cancer
Isaac NardiDan J Raz

Abstract

In the last decade, it has become clear that epigenetic changes act together with genetic mutations to promote virtually every stage of tumorigenesis and cancer progression. This knowledge has triggered searches for "epigenetic drugs" that can be developed into new cancer therapies. Here we report that triptolide reduced lung cancer incidence from 70% to 10% in a Fen1 E160D transgenic mouse model and effectively inhibited cancer growth and metastasis in A549 and H460 mouse xenografts. We found that triptolide induced lung cancer cell apoptosis that was associated with global epigenetic changes to histone 3 (H3). These global epigenetic changes in H3 are correlated with an increase in protein expression of five Wnt inhibitory factors that include WIF1, FRZB, SFRP1, ENY2, and DKK1. Triptolide had no effect on DNA methylation status at any of the CpG islands located in the promoter regions of all five Wnt inhibitory factors. Wnt expression is implicated in promoting the development and progression of many lung cancers. Because of this, the potential to target Wnt signaling with drugs that induce epigenetic modifications provides a new avenue for developing novel therapies for patients with these tumor types.

References

Jul 21, 1999·Journal of the National Cancer Institute·S S Hecht
Feb 14, 2006·The Journal of Biological Chemistry·Sandy D WesterheideRichard I Morimoto
Feb 27, 2007·The Journal of Thoracic and Cardiovascular Surgery·Jae KimDavid Jablons
Jun 26, 2007·Nature Medicine·Li ZhengBinghui Shen
Nov 26, 2008·Cold Spring Harbor Symposia on Quantitative Biology·R NusseY Kalani
Jul 22, 2009·Developmental Cell·Bryan T MacDonaldXi He
Jun 29, 2010·Annals of Oncology : Official Journal of the European Society for Medical Oncology·L CrinòUNKNOWN ESMO Guidelines Working Group
Mar 23, 2012·Cold Spring Harbor Perspectives in Biology·Paul Polakis
Dec 3, 2013·Asian Pacific Journal of Cancer Prevention : APJCP·Ousman TamgueYan-Ming Wei
Dec 7, 2013·Journal of the National Cancer Institute·David J Stewart
Jan 9, 2014·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal
Mar 13, 2014·Cancer Chemotherapy and Pharmacology·John M FidlerMichael Andreeff
May 24, 2014·Cell Death & Disease·I RamachandranL Queimado
Dec 3, 2014·Current Opinion in Structural Biology·Tomas Malinauskas, E Yvonne Jones
Jul 1, 2015·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Sulagna Banerjee, Ashok Saluja
Aug 25, 2015·The Annals of Thoracic Surgery·Theresa A RenoDan J Raz

❮ Previous
Next ❯

Citations

May 28, 2019·Journal of Experimental & Clinical Cancer Research : CR·Xia LiangXiangwei Gao
Feb 26, 2021·Toxicology and Applied Pharmacology·Rasha Irshad, Mohammad Husain
Apr 16, 2019·Oncology Research·Jie WeiZhijie Xu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Epigenetics & Methyl-CpG (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. Here is the latest research on cancer epigenetics and methyl-CpG binding proteins including ZBTB38.

Cell Signaling & Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. This feed covers the latest research on signaling and epigenetics in cell growth and cancer.

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cancer Epigenetics

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Cancer Epigenetics and Senescence (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may be involved in regulating senescence in cancer cells. This feed captures the latest research on cancer epigenetics and senescence.