Effects of 2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethylchalcone from Syzygium nervosum Seeds on Antiproliferative, DNA Damage, Cell Cycle Arrest, and Apoptosis in Human Cervical Cancer Cell Lines

Abstract

2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (DMC), a natural product derived from Syzygium nervosum A. Cunn. ex DC., was investigated for its inhibitory activities against various cancer cell lines. In this work, we investigated the effects of DMC and available anticervical cancer drugs (5-fluorouracil, cisplatin, and doxorubicin) on three human cervical cancer cell lines (C-33A, HeLa, and SiHa). DMC displayed antiproliferative cervical cancer activity in C-33A, HeLa, and SiHa cells, with IC50 values of 15.76 ± 1.49, 10.05 ± 0.22, and 18.31 ± 3.10 µM, respectively. DMC presented higher antiproliferative cancer activity in HeLa cells; therefore, we further investigated DMC-induced apoptosis in this cell line, including DNA damage, cell cycle arrest, and apoptosis assays. As a potential anticancer agent, DMC treatment increased DNA damage in cancer cells, observed through fluorescence inverted microscopy and a comet assay. The cell cycle assay showed an increased number of cells in the G0/G1 phase following DMC treatment. Furthermore, DMC treatment-induced apoptosis cell death was approximately three- to four-fold higher compared to the untreated group. Here, DMC represented a compound-induced apoptosis for cell death in the HeLa cervical cancer cell line. Our findings suggest that DMC, a phytochemical agent, is a potential candidate for antiproliferative cervical cancer drug development.

PLGA-Quercetin Nano-Formulation Inhibits Cancer Progression via Mitochondrial Dependent Caspase-3,7 and Independent FoxO1 Activation with Concomitant PI3K/AKT Suppression

“…Cell viability data showed that QNPs were more toxic to cancer cells than Q, revealing the enhanced therapeutic capability of QNPs. It has been considered that phytochemicals possess the property to control cancer progression via induction of apoptosis, mitochondrial dysfunction, caspase activation, cell cycle arrest, and gene expression alteration [ 32 ]. Our results revealed that QNPs showed greater apoptotic effect, mitochondrial dysfunction, caspase activation, and G2 phase cell cycle arrest over bulk quercetin at all the concentrations, demonstrating the potential therapeutic capability of QNPs in cervical and breast cancer.…”

Chalcone-Acridine Hybrid Suppresses Melanoma Cell Progression via G2/M Cell Cycle Arrest, DNA Damage, Apoptosis, and Modulation of MAP Kinases Activity

“…Our results showed that chalcone 1C -induced a significant increase in ATM phosphorylation followed by its downstream molecules phosphorylation including histone H2A.X at Ser139 (γ-H2A.X), p53 and p21 proteins, SMC1, indicating that this chalcone has DNA toxicity. Recently, different chalcone hybrids have been reported to have an antiproliferative effect associated with DNA damage [ 48 , 70 ]. In addition, DDR is also associated with the activation of PARP, an enzyme involved in DNA repair [ 71 ].…”

Phytochemical composition, antioxidant, antibacterial, and enzyme inhibitory activities of organic extracts from flower buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry

“…The ethanolic extract of the flower buds was also found to have potent anti-inflammatory and antiosteoclastogenic effects (Tran et al, 2019a , 2019b ), antioxidant and antibacterial properties against both Gram-positive and Gram-negative bacteria (Dung et al, 2008 ). A main flavonoid compound, 2′,4′-dihydroxy6′-methoxy-3′,5′-dimethylchalcone (DMC), isolated from the flower buds and seeds, was proven to serve as a chemotherapeutic agent for the prevention or treatment of lung, liver, pancreatic, and cervical cancers (Ye et al, 2004 ; Tuan et al, 2019 ; Utama et al, 2022 ) and inflammatory diseases (Tran et al, 2019a ). Due to the safety and effective pharmacological activity of different solvent preparations from the flower buds of C. operculatus , the present study was conducted to obtain extracts from the flower buds using different solvents (hexane, chloroform, ethyl acetate, butanol, ethanol, methanol, and water) and evaluate the phytochemical content of these extracts (flavonoids, phenolics, tannins, triterpenoid saponins, and alkaloids), their antioxidant capacity, growth inhibitory activity against Helicobacter pylori and Salmonella typhimurium , and enzyme inhibitory effect on H. pylori -urease and α-glucosidase.…”