Histone Study Unveils Curcumin & DMC's Potential in Cancer Therapy

Cancer remains a formidable global health challenge, demanding innovative and targeted therapeutic strategies. While genetic mutations have long been recognized as drivers of cancer, emerging evidence suggests that epigenetic alterations play a critical role in oncogenesis. These epigenetic changes encompass DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA regulation, collectively influencing patterns of gene expression.

Curcumin, a naturally occurring compound found in turmeric, has displayed remarkable potential in this field. However, its clinical utility has been hampered by a significant limitation—poor bioavailability resulting from inadequate absorption, rapid metabolism, and swift systemic elimination. Researchers have been diligently working to develop more stable analogs of curcumin, and one of the most promising candidates to emerge is dimethoxycurcumin, or DMC. This compound offers improved stability and solubility compared to its natural counterpart, opening up new possibilities for cancer treatment.

In a recent study, a group of scientists from the University of Charleston, West Virginia State University, and Edward Via College of Osteopathic Medicine (VCOM) explored the effects of both curcumin and DMC on histone modifications, a crucial component of epigenetic regulation. Their findings, published in the Journal of Cellular and Molecular Medicine, could shed light on the potential use of these compounds in cancer treatment.

To uncover the epigenetic effects of curcumin and DMC, the team employed human leukemia cell lines as their experimental model. They exposed both compounds to varying concentrations, meticulously measuring changes in histone posttranslational modifications and quantifying a total of 95 different histone marks. Additionally, they assessed the enzymatic activity of histone lysine methyltransferases (HMTs) and histone lysine demethylases (KDMs) using EpigenTek's HMT and KDM activity/inhibition kits.

The research findings proved to be intriguing. Both compounds significantly impacted histone modifications, including lysine methylation, acetylation, arginine, and glutamine methylation. While some modifications responded similarly to both compounds, others exhibited distinct alterations.

Histone lysine methyltransferases (HMTs) are enzymes that play a pivotal role in modifying specific histone marks, such as H3K4, H3K9, and H3K27. Astonishingly, the researchers found that both curcumin and DMC profoundly affected the activity of these enzymes. They inhibited the function of HMTs, potentially resulting in significant changes in gene expression.

Unexpectedly, curcumin and DMC also activated histone lysine demethylases (KDMs), including LSD1, JARID1, and JMJD2, which target H3K4 and H3K9 marks. This activation of KDMs introduced another layer to the compounds' epigenetic influence, potentially leading to decreased methylation at these marks and further changes in gene expression.

These findings represent a breakthrough in cancer research and therapy. By modulating a wide range of histone modifications and affecting both HMTs and KDMs, curcumin and its analog DMC offer a multifaceted approach to addressing epigenetic dysregulations in cancer.

The simultaneous ability to inhibit HMTs and activate KDMs holds the promise of overcoming drug resistance, a formidable challenge in cancer treatment. This dual action on epigenetic regulators suggests that curcumin and DMC could become potent tools in the fight against cancer.

While further research is imperative, including animal studies and clinical trials, these compounds provide hope for more effective and personalized cancer treatments. As cancer treatment advances, discoveries like this bring us closer to improved treatments that offer hope to patients and their families.

Source:
Sawesi S. et. al. (October 2022). Modulation of the activity of histone lysine methyltransferases and demethylases by curcumin analog in leukaemia cells. J Cell Mol Med.