Discovery of novel xanthohumol C derivatives regulating XRCC2 transcription and expression for the treatment of colorectal cancer.

Bioorg Med Chem

State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China. Electronic address:

Published: December 2024

X-ray repair cross-complementing 2 (XRCC2), a critical protein in homologous recombination (HR), plays a significant role in the occurrence, progression, and drug resistance of colorectal cancer (CRC). In this study, a series of xanthohumol C derivatives were synthesized, and their anticancer activity was evaluated. The results revealed that A33 demonstrated the potent anticancer activity and effectively inhibited the proliferation of CRC cells in vitro. Mechanistic investigations revealed that A33 suppressed the transcription and expression of XRCC2, resulting in cell cycle delay and the accumulation of DNA damage, ultimately leading to cell proliferation inhibition. Furthermore, A33 displayed high safety, favorable bioavailability (F = 37.51 %), and potent tumor growth inhibition in vivo, which highlighting its potential as a candidate for the development of novel anti-CRC therapies.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmc.2024.118048DOI Listing

Publication Analysis

Top Keywords

xanthohumol derivatives
8
transcription expression
8
colorectal cancer
8
anticancer activity
8
revealed a33
8
discovery novel
4
novel xanthohumol
4
derivatives regulating
4
regulating xrcc2
4
xrcc2 transcription
4

Similar Publications

Discovery of novel xanthohumol C derivatives regulating XRCC2 transcription and expression for the treatment of colorectal cancer.

Bioorg Med Chem

December 2024

State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China. Electronic address:

X-ray repair cross-complementing 2 (XRCC2), a critical protein in homologous recombination (HR), plays a significant role in the occurrence, progression, and drug resistance of colorectal cancer (CRC). In this study, a series of xanthohumol C derivatives were synthesized, and their anticancer activity was evaluated. The results revealed that A33 demonstrated the potent anticancer activity and effectively inhibited the proliferation of CRC cells in vitro.

View Article and Find Full Text PDF

The demand for bioactive secondary metabolites of natural origin is increasing every day. Micropropagation could be a strategy to respond more quickly to market demands, regardless of seasonality. This research aims to evaluate in vitro-grown plants of two hop varieties, namely Columbus and Magnum, as a potential source of bioactive compounds.

View Article and Find Full Text PDF

Xanthohumol (XTH, ), a major prenylated chalcone in hops, has attracted considerable interests because of its pharmaceutical potency. To explore more related derivatives of XTH, its biotransformation was performed using the microbial model. Fungus sp.

View Article and Find Full Text PDF

Cancer growth is dependent on angiogenesis, the formation of new blood vessels, which represents a hallmark of cancer. After this concept was established in the 1970s, inhibition of tumor development and metastases by blocking the neoangiogenic process has been an important approach to the treatment of tumors. However, antiangiogenic therapies are often administered when cancer has already progressed.

View Article and Find Full Text PDF

Xanthohumol-A Miracle Molecule with Biological Activities: A Review of Biodegradable Polymeric Carriers and Naturally Derived Compounds for Its Delivery.

Int J Mol Sci

March 2024

Chair and Department of the Pharmaceutical Chemistry and Biomaterials, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Str., 02-097 Warsaw, Poland.

Xanthohumol (Xn), a prenylated chalcone found in Hop ( L.), has been shown to have potent anti-aging, diabetes, inflammation, microbial infection, and cancer properties. Unfortunately, this molecule has undesirable characteristics such as inadequate intake, low aqueous solubility, and a short half-life.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!