Genetic variations along with epigenetic modifications of DNA are involved in colorectal cancer (CRC) development and progression. CRC is the fourth leading cause of cancer-related deaths worldwide. Initiation and progression of CRC is the cumulation of a variety of genetic and epigenetic changes in colonic epithelial cells. Colorectal carcinogenesis is associated with epigenetic aberrations including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs. Recently, epigenetic modifications have been identified like association of hypermethylated gene Claudin11 (CLDN11) with metastasis and prognosis of poor survival of CRC. DNA methylation of genes CMTM3, SSTR2, MDF1, NDRG4 and TGFB2 are potential epigenetic biomarkers for the early detection of CRC. Tumor suppressor candidate 3 (TUSC3) mRNA expression is silenced by promoter methylation, which promotes epidermal growth factor receptor (EGFR) signaling and rescues the CRC cells from apoptosis and hence leading to poor survival rate. Previous scientific evidences strongly suggest epigenetic modifications that contribute to anticancer drug resistance. Recent research studies emphasize development of drugs targeting histone deacetylases (HDACs) and DNA methyltransferase inhibitors as an emerging anticancer strategy. This review covers potential epigenetic modification targeting chemotherapeutic drugs and probable implementation for the treatment of CRC, which offers a strong rationale to explore therapeutic strategies and provides a basis to develop potent antitumor drugs.

Chemotherapy side effects, medication resistance, and tumor metastasis impede the advancement of cancer treatments, resulting in a poor prognosis for cancer patients. In the last decade, nanoparticles (NPs) have emerged as a promising drug delivery system. Swertia chirayita has long been used as a treatment option to treat a variety of ailments. Zinc oxide nanoparticles (ZnO-NPs) were synthesized from ethanolic and methanolic extract of S. chirayita leaves. ZnO-NPs were characterized using UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron Microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), and X-ray diffraction (XRD). Its anti-cancer activities were analyzed using cytotoxicity assays [MTT assay and acridine orange (AO) staining] and quantitative real-time PCR (qRT-PCR) using colorectal cancer (CRC) cells (HCT-116 and Caco-2) and control cells (HEK-293). The ZnO-NPs synthesized from the ethanolic extract of S. chirayita have an average size of 24.67 nm, whereas those from methanolic extract have an average size of 22.95 nm with a spherical shape. MTT assay showed NPs’ cytotoxic potential on cancer cells (HCT-116 and Caco-2) when compared to control cells (HEK-293). The IC₅₀ values of ethanolic and methanolic extract ZnO-NPs for HCT-116, Caco-2, and HEK-293 were 34.356 ± 2.71 and 32.856 ± 2.99 μg/ml, 52.15 ± 8.23 and 63.1 ± 12.09 μg/ml, and 582.84 ± 5.26 and 615.35 ± 4.74 μg/ml, respectively. Acridine orange staining confirmed the ability of ZnO-NPs to induce apoptosis. qRT-PCR analysis revealed significantly enhanced expression of E-cadherin whereas a reduced expression of vimentin and CDK-1. Altogether, these results suggested anti-cancer properties of synthesized ZnO-NPs in CRC.

Curcumin is a nutraceutical known to have numerous medicinal effects including anticancer activity. However, due to its poor water solubility and bioavailability, the therapeutic impact of curcumin against cancer, including breast cancer, has been constrained. Encapsulating curcumin into chitosan nanoparticles (CHNPs) is an effective method to increase its bioavailability as well as antitumorigenic activity. In the current study, the effects of curcumin-encapsulated CHNPs (Cur-CHNPs) on cell migration, targeted homing and tumor growth were examined using in vitro and in vivo breast cancer models. Cur-CHNPs possessed a monodispersed nature with long-term colloidal stability, and demonstrated significant inhibition of cell viability in vitro, which was potentiated by 5-Fluorouracil (5-FU). Outcomes of the in vivo imaging studies confirmed effective tumor targeting and retention ability of Cur-CHNPs, thereby suppressing breast tumor growth in mice models. Overall, the results demonstrated that Cur-CHNPs could be an effective candidate drug formulation for management of breast cancer.