A novel curcumin analog inhibits canonical and non-canonical functions of telomerase through STAT3 and NF-κB inactivation in colorectal cancer cells

Oncotarget
Seyung S ChungJaydutt V Vadgama

Abstract

Curcumin is a biologically active polyphenol that exists in Indian spice turmeric. It has been reported that curcumin exerted anti-inflammatory, anti-oxidant and anti-cancer effects in numerous in vitro and in vivo studies. However, it is not well-understood the molecular mechanism of curcumin for the cancer stem cells and telomerase in colorectal cancer. In this study, compound 19, a nitrogen-containing curcumin analog, was used to treat human colorectal cancer cells. Compound 19 showed a greater anti-proliferative activity than curcumin while displayed no significant toxicity toward normal human colon epithelial cells. Compound 19 exerted anti-inflammatory activities by deactivating STAT3 and NF-κB. In cancer stem cell populations, CD44, Oct-4 and ALDHA1 expressions were abolished upon treating with compound 19. Cancer stem cell biomarkers CD51 and CD133 positive populations were reduced and telomerase activities were decreased with the reduced STAT3 binding to hTERT promoters. This means compound 19 dually inhibits canonical and non-canonical functions of telomerase. Furthermore, compound 19 treatments induced cell cycle arrest at G1 phase and apoptosis. Human apoptosis-related array screening revealed that activated caspase...Continue Reading

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Citations

May 20, 2020·Frontiers in Pharmacology·Adhimoolam KarthikeyanTaesun Min
Jul 4, 2020·Signal Transduction and Targeted Therapy·Zhe ZhangCanhua Huang
Oct 29, 2020·Journal of Experimental & Clinical Cancer Research : CR·Longgang WangLei Zhou
Apr 19, 2021·Molecular and Cellular Biochemistry·Gayathri ChalikondaYun Suk Huh
Jun 27, 2021·Phytotherapy Research : PTR·Korosh MorshediHamed Mirzaei

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Methods Mentioned

BETA
FACS
flow cytometry
immunoprecipitation
electrophoretic mobility shift assay
immunoprecipitation assay
ChIP
PCR
ubiquitination
RNA-seq
Assay

Software Mentioned

image J
CLC Genomics Workbench
Ensembl GRCH37
Quantity One

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