Quercetin-3-Glucoside Extracted from Apple Pomace Induces Cell Cycle Arrest and Apoptosis by Increasing Intracellular ROS Levels.
Arti NileShivraj Hariram NileJuhyun ShinGyunseok ParkJae-Wook OhPublished in: International journal of molecular sciences (2021)
Cervical cancer is a life-threatening disease and the fourth most common cancer among women worldwide. Apple pomace is a multifunctional phenolic compound possessing effective biological activity against cervical cancer cells. This study aimed to investigate the anticancer effects of quercetin-3-glucoside (Q3G) extracted from apple pomace in HeLa cell lines and analyze its molecular mechanisms. High-performance liquid chromatography revealed that Q3G, coumaric acid, phloridzin, quercetin, and phloretin are the major polyphenolic compounds constituting apple pomace. Among them, Q3G possessed the greatest antioxidant and anti-inflammatory effects in vitro and exhibited significant cytotoxic effects in HeLa cells in a dose-and time-dependent manner. Flow cytometric analysis indicated that Q3G induced cell cycle arrest at the S phase in a time-dependent manner by altering cyclin-dependent kinase 2. Moreover, it induced apoptosis via chromosomal DNA degradation and increased reactive oxygen species generation. Furthermore, Q3G treatment altered the apoptosis-associated protein expression in the cells by activating caspase-9/-3, downregulating anti-apoptosis protein B-cell lymphoma (Bcl)-2 expressions and up regulating the pro-apoptotic Bcl-2-associated X protein. BH3-interacting domain death agonist cleavage occurred prior to the degradation of an anti-apoptotic Mu-2-related death-inducing gene involved in cell death signaling. Consequently, apple pomace Q3G holds promise as an anti-inflammatory and anticancer agent for treating cervical cancer.
Keyphrases
- cell cycle arrest
- cell death
- induced apoptosis
- anti inflammatory
- reactive oxygen species
- high performance liquid chromatography
- signaling pathway
- oxidative stress
- endoplasmic reticulum stress
- pi k akt
- copy number
- papillary thyroid
- mass spectrometry
- drug delivery
- tandem mass spectrometry
- metabolic syndrome
- squamous cell carcinoma
- genome wide
- cell free
- diabetic rats
- type diabetes
- adipose tissue
- small molecule
- dna methylation
- binding protein
- single cell
- solid phase extraction
- lymph node metastasis
- machine learning
- cell proliferation
- cancer therapy
- ms ms
- stress induced
- smoking cessation