In summary, our work demonstrates that parthenolide induces both extrinsic and intrinsic apoptosis via ER stress signaling pathway in human NSCLC cells. Moreover, parthenolide induces stronger ER stress and apoptosis in cancer stem like cells which may account for its selective effect in apoptosis induction. Collect ively, this study provides important mechanistic insight into potential cancer treatment with parthenolide as well as our understanding for cancer stem cells. Background Colorectal cancer is the third most common can cer and the second leading cause of cancer death in the world. CRC is a consequence of genetic events including gene mutations and epigenetic alterations that transform colonic epithelial cells into adenocarcinoma cells.

The early detection of CRC is most important in cancer patients to reduce cancer mortality. Different stages of CRC have different prognoses selleckchem and the effects of adju vant chemotherapy differ between CRC stage II and stage III. Current CRC chemotherapy consists of a combination of cytotoxic DNA antimetabolites, such as 5 fluorouracil, leucovorin, or oxaliplatin. However, the best combination of these anticancer drugs is still not fully established. To achieve this, epigenetic DNA methylation was reported as a suitable approach for a better understanding of CRC progression and thera peutic targets. A great number of studies have focused on the epigen etic alterations of tumor suppressor genes in the regula tion of cancer initiation and progression.

Gene specific methylation changes in promoter CpG WIKI4 Tie2 kinase inhibitor regions have been largely related to biological processes of tumor progres sion including cell proliferation, communication, adhe sion, mobility, signal transduction, and drug resistance. Aberrant methylation of CpG islands in the promoter or exon 1 regions of tumor suppressor genes has been corre lated with transcriptional silencing of downstream genes in colorectal cancer. Many genes silenced by aberrant methylation, including CDKN2A, THBS, and SFRP have been proposed to be associated with CRC tumorigenesis. Moreover, promoter methylation was also re ferred to as the CpG island methylator phenotype. CIMP positive CRC was distinguished from CIMP negative CRC patients by clinicopathological fac tors, and CIMP was associated with development of the serrated pathway of CRC. Clinically, several CIMPs containing MLH1, and microsat ellite instability were characterized to be associated with CRC prognosis. Furthermore, a panel of CIMP in cluding RUNX3, CACNA1G, IGF2, and MLH1 consists of specific markers for clinical trials.