Том 24, № 17 (2024)

Objective:Enicostemma hyssopifolium (E. hyssopifolium) contains several bioactive compounds with anti-cancer activities. This study was performed to investigate the molecular effects of E. hyssopifolium on HPV18-containing HeLa cells.

Methods:The methanol extract of E. hyssopifolium whole plant was tested for cytotoxicity by MTT assay. A lower and higher dose (80 and 160 µg/mL) to IC50 were analyzed for colonization inhibition (Clonogenic assay), cell cycle arrest (FACS analysis), and induction of apoptosis (AO/EtBr staining fluorescent microscopy and FACS analysis) and DNA fragmentation (comet assay). The HPV 18 E6 gene expression in treated cells was analyzed using RT-PCR and qPCR.

Results:A significant dose-dependent anti-proliferative activity (IC50 - 108.25±2 µg/mL) and inhibition of colony formation cell line were observed using both treatments. Treatment with 80 µg/mL of extract was found to result in a higher percent of cell cycle arrest at G0/G1 and G2M phases with more early apoptosis, while 160 µg/mL resulted in more cell cycle arrest at SUBG0 and S phases with late apoptosis for control. The comet assay also demonstrated a highly significant increase in DNA fragmentation after treatment with 160 µg/mL of extract (tail moments-19.536 ± 17.8), while 80 µg/mL of extract treatment showed non-significant tail moment (8.152 ± 13.0) compared to control (8.038 ± 12.0). The RT-PCR and qPCR results showed a significant reduction in the expression of the HPV18 E6 gene in HeLa cells treated with 160 µg/mL of extract, while 80 µg/mL did not show a significant reduction.

Conclusion:The 160 µg/mL methanol extract of E. hyssopifolium demonstrated highly significant anti-cancer molecular effects in HeLa cells.

Background:Non-small-cell lung cancer is a prevalent malignancy associated with significant morbidity and mortality rates. Tryptanthrin and its derivatives have exhibited potent antitumor activity.

Objective:This study aims to investigate the inhibitory effect of a novel synthesized tryptanthrin derivative D6 on proliferation and the possible mechanism of human non-small cell lung cancer cell lines (A549) in vitro.

Methods:In this study, MTT assay, cell migration, colony formation assay, cell cycle analysis, cell apoptosis, JC- 1 staining assay, reactive oxygen species analysis, proteomics, western blotting, high content screening and absorption titrations analysis were performed.

Results:We found that D6 inhibited both the proliferation and migration, induced cell cycle arrest in the G2/M phase, increased levels of ROS, decreased mitochondrial membrane potential, and promoted apoptosis in A549 cells. Further mechanistic studies found that D6 reduced EGFR expression in A549 cells and inhibited the EGFR pathway by decreasing phosphorylation levels of EGFR, Stat3, AKT and Erk1/2. Moreover, DNA damage induced by D6 involved an increase in p53/MDM2 ratio and concentration-dependent accumulation of micronuclei.

Conclusion:D6 demonstrated significant antitumor activity against A549 cells by inhibiting the EGFR signaling pathway, inducing DNA damage, and subsequently leading to oxidative stress, apoptosis, and cell cycle arrest. Our findings suggest that D6 exhibits potential as an NSCLC drug, owing to its attributes such as antiproliferative activity and ability to induce apoptosis by attenuating the EGFR-mediated signaling pathway.

Introduction:Globally, about 8.2 million cancer-related deaths are recorded annually. Sadly, most of the deaths result from the toxicity of most chemotherapeutic agents. Hence, there are growing demands for chemotherapeutic agents with high specificity and selectivity. This study was designed to assess the cytotoxic potential of Detarium microcarpum and isolate cytotoxic compounds with better selectivity profiles.

Methods:Detarium microcarpum Stem bark (DMS) was collected and authenticated at the Forest Herbarium Ibadan (FHI), and a voucher (FHI-111954) was issued. Dried DMS was pulverized and extracted into 70% methanol. The extract was partitioned into hexane, dichloromethane, and ethyl acetate fractions. The cytotoxicities of the extract, fractions, and isolated compounds were determined. The cytotoxicity of the isolated compounds was tested against different cell lines, including human breast (AU565 and MDA MB231), oral adenosquamous (CAL27), and cervical (HeLa) cancer cells, as well as healthy (3T3) non-cancer cells.

Results:Methyl gallate, eriodictyol, quercetin, quebrachitol, catechin, catechin gallate, and gallic acid, isolated from dichloromethane and ethyl acetate fractions, displayed weak cytotoxicity against breast (AU565 and MDAMD- 231) and cervical (HeLa) cancer cell lines. Interestingly, all the compounds, except gallic acid (48.91±4.51% inhibition), displayed potent cytotoxicity on oral cancer cells. Methyl gallate and quercetin displayed the highest activity, with IC50 values of 89.57±1.98µM and 78.19±1.49µM, respectively. Interestingly, all the compounds were not toxic to healthy non-cancer (3T3) cells.

Conclusion:The compounds displayed anticancer activity specific to oral cancer cells and were highly selective for cancer cells without causing significant toxicity to healthy non-cancer cells.