Curcumin from Turmeric Rhizome: A Potential Modulator of DNA Methylation Machinery in Breast Cancer Inhibition

One of the most systematically studied bioactive nutraceuticals for its benefits in the management of various diseases is the turmeric-derived compounds: curcumin. Turmeric obtained from the rhizome of a perennial herb Curcuma longa L. is a condiment commonly used in our diet. Curcumin is well known for its potential role in inhibiting cancer by targeting epigenetic machinery, with DNA methylation at the forefront. The dynamic DNA methylation processes serve as an adaptive mechanism to a wide variety of environmental factors, including diet. Every healthy tissue has a precise DNA methylation pattern that changes during cancer development, forming a cancer-specific design. Hypermethylation of tumor suppressor genes, global DNA demethylation, and promoter hypomethylation of oncogenes and prometastatic genes are hallmarks of nearly all types of cancer, including breast cancer. Curcumin has been shown to modulate epigenetic events that are dysregulated in cancer cells and possess the potential to prevent cancer or enhance the effects of conventional anti-cancer therapy. Although mechanisms underlying curcumin-mediated changes in the epigenome remain to be fully elucidated, the mode of action targeting both hypermethylated and hypomethylated genes in cancer is promising for cancer chemoprevention. This review provides a comprehensive discussion of potential epigenetic mechanisms of curcumin in reversing altered patterns of DNA methylation in breast cancer that is the most commonly diagnosed cancer and the leading cause of cancer death among females worldwide. Insight into the other bioactive components of turmeric rhizome as potential epigenetic modifiers has been indicated as well.

Dual Aromatase-Sulphatase Inhibitors (DASIs) for the Treatment of Hormone Dependent Breast Cancer

: Breast cancer is the most frequent diagnosed cancer in women and the second most common form of cancer, causing death after lung cancer, all across the globe at an alarming rate. The level of estrogens, in breast cancer tissues of postmenopausal women is 10-40 folds higher than the non-carcinogenic breast tissues. As a result of this greater level of estrogen, breast tissue becomes more prone to develop breast cancer; mainly estradiol plays a significant role in the initiation and development of hormone dependent breast cancer. Androstenedione, Adrenal dehydroepiandrosterone sulfate and estrone-sulfate also plays an important role of precursor for estrogen biosynthesis. Estrogens deprivation exhibits an attractive phenomena in the advancement of most ideal therapeutics for the treatment of breast cancer. Inhibition of aromatase and sulphatase emerged as attractive therapy for the treatment of hormone dependent breast cancer via deprivation of estrogen by different pathways. The cocktail of aromatase and sulphatase inhibitors known as dual aromatase-sulphatase inhibitors (DASIs) emerged as an attractive approach for the effective estrogen deprivation. The present review article focused on the journey of dual aromatase-sulphatase inhibitors from the beginning to till date (2020). Keeping in view the key observations, this review may be helpful for medicinal chemists to design and develop new and efficient dual aromatase-sulphatase inhibitors for the possible treatment of hormone-related breast cancer.

Platinum chemotherapy induces lymphangiogenesis to prime tissues for tumor metastasis

Chemotherapy has been used to inhibit cancer growth for decades, but emerging evidence shows it can affect the tumor stroma unintentionally promoting cancer malignancy. After treatment of primary tumors, remaining drug drains via lymphatics. Though all drugs interact with the lymphatics, we know little of their impact on them. Here, we show a previously unknown effect of platinums, a widely used chemotherapeutic, to directly induce systemic VEGFR3-dependent lymphangiogenesis. These changes are dose-dependent, long-lasting, and occur in healthy and cancerous tissue in multiple mouse models of breast cancer. We saw similar effects in human ovarian and breast cancer patients whose treatment regimens included platinums. Carboplatin treatment results in lymphatic hyperplasia and secretion of pro-chemotactic factors in lymph nodes. Carboplatin treatment of healthy mice prior to mammary tumor inoculation increases cancer metastasis. These findings have broad-reaching implications for cancer patients receiving platinums and support the inclusion of anti-VEGFR3 therapy into treatment regimens.SummaryPlatinum chemotherapy induces lymphangiogenesis priming tissues for metastasis of breast cancer. Inhibition of VEGFR3 via antibody blockade can reverse these effects.