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.

The present study was aimed to assess cellular and molecular events involved in the chemopreventive activities of β-cryptoxanthin derived from mandarin oranges (Citrus unshiu Marc.) on human cervical carcinoma (HeLa) cells. In vitro experiments established that β-cryptoxanthin significantly inhibited the proliferation of HeLa cells with the IC₅₀ value of 4.5 and 3.7 µM after 24 and 48 h of treatments, respectively. β-cryptoxanthin-treated HeLa cells exhibited enhanced levels of oxidative stress correlated with significant downregulation of anti-apoptotic Bcl-2, and upregulation of pro-apoptotic Bax mRNA expression. Moreover, β-cryptoxanthin triggered nuclear condensation and disruption of the integrity of the mitochondrial membrane, upregulated caspase-3, -7, and -9 mRNA, and enhanced activation of caspase-3 proteins, resulting in nuclei DNA damage and apoptosis of HeLa cells. Remarkably, TUNEL assay carried out to detect nuclei DNA damage showed 52% TUNEL-positive cells after treatment with a physiological concentration of β-cryptoxanthin (1.0 μM), which validates its potential as an anticancer drug of natural origin.

Cinnamon is a natural spice with a wide range of pharmacological functions, including anti-microbial, antioxidant, and anti-tumor activities. The aim of this study is to investigate the effects of cinnamaldehyde-rich cinnamon extract (CRCE) on the colorectal cancer cell lines HCT 116 and HT-29. The gas chromatography mass spectrometry analysis of a lipophilic extract of cinnamon revealed the dominance of trans-cinnamaldehyde. Cells treated with CRCE (10–60 µg/mL) showed significantly decreased cell viability in a time- and dose-dependent manner. We also observed that cell proliferation and migration capacity were inhibited in CRCE-treated cells. In addition, a remarkable increase in the number of sub-G₁-phase cells was observed with arrest at the G₂ phase by CRCE treatment. CRCE also induced mitochondrial stress, and finally, CRCE treatment resulted in activation of apoptotic proteins Caspase-3, -9, and PARP and decreased levels of mu-2-related death-inducing gene protein expression with BH3-interacting domain death agonist (BID) activation.

Carotenoids have been suggested to have either anti- or pro-oxidative effects in several cancer cells, and those effects can trigger an unbalanced reactive oxygen species (ROS) production resulting in an apoptotic response. Our study aimed to evaluate the effect of the well-known carotenoid 3, 3′-dihydroxy-β, β’-carotene-4, 4-dione (astaxanthin, AXT) on glioblastoma multiforme (GBM) cells, especially as a pretreatment of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), that was previously shown to increase ROS and to induce apoptosis in cancer cells. We found that AXT by itself did not trigger apoptosis in four investigated GBM cell lines upon a 24 h treatment at various concentrations from 2.5 to 50 µM. However, in U251-MG and T98-MG GBM cells, pretreatment of 2.5 to 10 µM AXT sensitized cells to TRAIL treatment in a statistically significant manner (p < 0.05) while it did not affect CRT-MG and U87-MG GBM cells. We further compared AXT-sensitive U251-MG and -insensitive CRT-MG response to AXT and showed that 5 µM AXT treatment had a beneficial effect on both cell lines, as it enhanced mitochondrial potential and TRAIL treatment had the opposite effect, as it decreased mitochondrial potential. Interestingly, in U251-MG, 5 µM AXT pretreatment to TRAIL-treated cells mitochondrial potential further decreased compared to TRAIL alone cells. In addition, while 25 and 50 ng/mL TRAIL treatment increased ROS for both cell lines, pretreatment of 5 µM AXT induced a significant ROS decrease in CRT-MG (p < 0.05) while less effective in U251-MG. We found that in U251-MG, superoxide dismutase (SOD) 2 expression and enzymatic activity were lower compared to CRT-MG and that overexpression of SOD2 in U251-MG abolished AXT sensitization to TRAIL treatment. Taken together, these results suggest that while AXT acts as an ROS scavenger in GBM cell lines, it also has some role in decreasing mitochondrial potential together with TRAIL in a pathway that can be inhibited by SOD2.