Formation Of Apoptotic Bodies Research Articles

Inhibitory Effects of Royal Jelly and Its Functional Components on the Proliferation of MKN-28 Gastric Cancer Cells.

Royal jelly (RJ) is a natural food product with nutritional value and anticancer activity. However, their effects on gastric cancer are unclear. Here, we show that treatment with 5-320 μg/mL of RJ, ethanol extract (RJEE), and protein hydrolyzate (RJPH) decreased the viability of MKN-28 gastric cancer cells, with a half-maximal inhibitory concentration of 123.22 μg/mL for RJEE. RJ, RJEE, and RJPH increase the lactate dehydrogenase release rate and change the morphology of the cells, resulting in cell shrinkage, nucleoplasm condensation, and the formation of apoptotic bodies. RJ and its functional components stagnated the cell cycle in the G0/G1 phase, accompanied by the accumulation of reactive oxygen species, decreased mitochondrial membrane potential, and increased expression levels of p53 and p21 proteins, caspase-3 activation, and apoptosis. Therefore, RJ, RJEE, and RJPH have potential inhibitory effects on the proliferation of gastric cancer cells.

Gingerol-zinc complex loaded 3D-printed calcium phosphate for controlled release application.

The therapeutic potential of natural medicines in treating bone disorders is well-established. Modifications in formulation or molecular structure can enhance their efficacy. Gingerol, an osteogenic active compound derived from ginger roots (Zingiber officinale), can form metal ion complexes. Zinc (Zn), a trace element that combats bacterial infections and promotes osteoblast proliferation, can be complexed with gingerol to form a G-Zn+2 complex. This study investigates a porous 3D-printed (3DP) calcium phosphate (CaP) scaffold loaded with the G-Zn+2 complex for drug release and cellular interactions. The scaffold is coated with polycaprolactone (PCL) to control the drug release. Diffusion-mediated kinetics results in 50% releaseof the G-Zn+2 complex over 6weeks. The G-Zn+2 complex demonstrates cytotoxicity against MG-63 osteosarcoma cells, indicated by the formation of apoptotic bodies and ruptured cell morphology on the scaffolds. G-Zn+2 PCL-coated scaffolds show a 1.2 ± 0.1-fold increase in osteoblast cell viability, and an 11.6 ± 0.5% increase in alkaline phosphatase compared to untreated scaffolds. Treated scaffolds also exhibit reduced bacterial colonization against Staphylococcus aureus bacteria, highlighting the antibacterial potential of the G-Zn+2 complex. The functionalized 3DP CaP scaffold with the G-Zn+2 complex shows significant potential for enhancing bone regeneration and preventing infections in low-load-bearing applications.

Fractionated Leaf Extracts of Ocimum gratissimum Inhibit the Proliferation and Induce Apoptosis of A549 Lung Adenocarcinoma Cells.

Previous in vitro studies in our laboratory demonstrated that ethyl acetate (P2) and water- soluble (PS/PT1) fractionated leaf extracts of Ocimum gratissimum inhibit the proliferation of prostate cancer cells. It has been reported that the crude aqueous extract induces apoptosis in lung adenocarcinoma cells; however, the efficacy of the fractionated extracts against these cells remains unclear. In the present study, we hypothesized that the ability of the fractionated extracts to inhibit proliferation and induce apoptosis is associated with the activation of pro-apoptotic proteins and induction of DNA condensation in A549 cells. Ocimum gratissimum was cultivated and its leaves were harvested, extracted, and fractionated to produce fractions P2 and PS/PT1. Anti-proliferative activity was assessed by direct cell count. For morphological characterization of apoptosis, 4',6-diamidino-2-phenylindole staining was employed. Western blot analysis was performed to evaluate the apoptotic activity of the fractionated extracts. In data generated from anti-proliferation studies, P2 significantly inhibited cell proliferation in a concentration-dependent manner; PS/PT1 elicited a decrease in the viability of cells, occurring at 500 µg/mL. 4',6-diamidino-2-phenylindole staining revealed the induction of apoptosis, as evidenced by the formation of apoptotic bodies. Increased levels of pro-apoptotic proteins were observed as the concentrations of the fractionated extracts increased. These results suggest that fractionated leaf extracts of Ocimum gratissimum inhibit the proliferation and induce apoptosis of A549 cells.

Multi-color two-laser super-resolution structured illumination microscopy for the visualization of multi-organelle in living cells.

In this study, we introduced a novel dual-laser multi-color imaging system. Integrated with a multi-channel filter wheel, this system compared three spectral decontamination algorithms (nonnegative matrix factorization [NMF], RCAN, and PICASSO) showcasing its efficacy in achieving four-color imaging with only two laser sources. Combined with a reliable image reconstruction algorithm, the spatial resolution of four channels super-resolution four-color images reached 130, 125, 133, and 132 nm, respectively. Lipid droplets, mitochondria, lysosomes, and nuclei from the mouse hepatocytes (AML12), human neuroblastoma cells (SH-SY5Y), mouse hippocampal neuronal cells (HT-22), and immortalized murine bone marrow-derived macrophages were imaged. At the same time, the chromatin condensation, nuclear contraction, DNA fragmentation, apoptotic body formation, as well as the fusion of Mito and Lyso involved in mitochondrial autophagy were observed in HT-22 and SH-SY5Y cells suffering oxidative stress. Our multi-color SIM imaging system establishes a powerful platform for dynamic organelle studies and other high-resolution investigations in live cells.

Toxicity and safety of rosemary (Rosmarinus officinalis): a comprehensive review.

Rosemary (Rosmarinus officinalis) contains alkaloids, phenolic acids, saponins, tannins, diterpenes, flavonoids, and essential oils and has antioxidant, anti-inflammatory, antibacterial, anticancer, neuroprotective, cardioprotective, and hepatoprotective effects. While rosemary is generally considered safe for consumption and topical application, allergic reactions and dermatitis have been reported in some individuals. This paper provides an in-depth review of the current studies on rosemary toxicity, shedding light on its potential adverse effects and underlying mechanisms. Google Scholar, PubMed, Scopus, and Web of Science were used to perform extensive research from the inception of these databases until February 2024. The toxicological effects explored include affecting several organs such as the liver and kidney by causing atrophic and degenerative changes, increasing blood urea nitrogen (BUN), aspartate aminotransferase (AST), and reducing total serum protein levels. Rosemary may induce reproductive toxicity by decreasing spermatogenesis in the testes, testosterone, sperm density, and motility. It might also trigger genotoxicity and anomalies in fetuses by increasing cytoplasmic membrane shrinkage, the formation of apoptotic bodies, internucleosomal deoxyribonucleic acid (DNA) fragmentation, and DNA ladder formation. While rosemary is considered safe for food preservation, caution is warranted regarding chronic and high doses due to potential adverse effects on the kidneys, liver, reproductive system, and teratology. Additionally, it underscores the significance of considering drug interactions. The article also highlights the importance of considering toxicological data in realistic exposure situations and discusses the relevance of these findings for human health. Hence, further research is recommended to enhance our understanding of the toxicity profile associated with rosemary.

Induction of Apoptosis and ROS Production in Liver Cancer Cells by Saponin Fraction from Alcea rosea L. Seeds

Background: Natural compounds are essential targets in anticancer research due to the toxic effects of current chemotherapy and drug resistance. Methods: Saponin extraction from Alcea rosea L. was carried out using 20% methanol and liquid-liquid extraction coupled with the Solid phase extraction (SPE) approach. The saponin fraction was explored for its cytotoxic activity against Huh-7 and MDA-MB-231 cancer cell lines and a non–cancer cell line (HUVEC). The cytotoxic activity and oxidative stress were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and 2,7 dichlorofluorescein diacetate dyes respectively. The apoptotic potential was investigated using DAPI and acridine orange-ethidium bromide dual staining. Result: The saponin fraction exhibited cytotoxic potential against the cell lines investigated. The IC50 values of the saponin fraction were 49.02, 300 and 325 µg\mL against Huh-7, MDA-MB-231 and HUVEC cell lines, respectively. The cytotoxicity for the extract was dose-dependent. The saponin fraction calculated selectivity index (SI) value indicated high selectivity towards Huh-7 cells (SI = 6.62) compared with normal HUVEC cells. Huh-7 cells treated with saponin fraction showed cellular and nuclear morphological changes, such as apoptotic body formation and chromatin condensation, as observed using light and fluorescent microscopy. However, further investigation is required to assess the the saponin fraction as a potential therapeutic agent.

Crotoxin induces cytotoxic effects in human malignant melanoma cells in both native and detoxified forms.

Introduction: Melanoma, a highly aggressive skin cancer originating in melanocytes, poses a significant threat due to its metastatic potential. While progress has been made in treating melanoma with targeted therapies and immunotherapies, challenges persist. Crotoxin (CTX), the principal toxin in Crotalus durissus terrificus snake venom, exhibits various biological activities, including anti-tumoral effects across multiple cancers. However, its clinical use is limited by toxicity. Thus, exploring alternatives to mitigate adverse effects is crucial. Methods and Results: This study investigates the antitumoral potential of CTX in its native and in a detoxified form, in melanoma cells. Firstly, we demonstrated that detoxified CTX presented reduced phospholipase activity. Both forms proved to be more cytotoxic to SK-MEL-28 and MeWo melanoma cells than non-tumoral cells. In SK-MEL-28 cells, where cytotoxic effects were more pronounced, native and detoxified CTX induced increased necrosis and apoptosis rates. We also confirmed the apoptosis death demonstrated by the activation of caspase-3 and 7, and the formation of apoptotic bodies. Furthermore, both CTX caused cell cycle arrest at the G2/M phase, interfering with melanoma cell proliferation. Cell migration and invasion were also suppressed by both CTX. These results confirm the antitumoral potential of CTX. Discussion: The maintenance of the antiproliferative effects in the detoxified version, with reduced enzymatic activity often liked to harm effects, supports further studies to identify active parts of the molecule responsible for the interesting effects without causing substantial toxic events, contributing to the future use of CTX-derived drugs with safety and efficacy.

Bioactivity responses to changes in mucus-associated bacterial composition between healthy and bleached Porites lobata corals

This study aims to investigate how bioactivities of the coral surface mucus layer (SML) respond to changes in mucus-associated bacterial communities between bleached and healthy Porites lobata corals in Nha Trang Bay, Vietnam. The findings suggested that significant shifts in the mucus-associated bacterial communities were related to changes in coral health states from bleached to healthy P. lobata colonies (p < 0.05), while bacterial compositions were not significantly different across seasons and locations (p > 0.05). Of which 8 genera, Shewanella, Fusibacter, Halodesulfovibrio, Marinifilum, Endozoicomonas, Litoribacillus, Algicola, and Vibrio were present only in the SML of bleached coral while absent in the SML of the healthy one. As compared with the bleached SML, the healthy SML demonstrated stronger antibacterial activity against a coral bleaching pathogen, V. coralliilyticus, higher antitumor activity against HCT116 cell accompanied with increased induction of cleaved PARP and accelerated cell nucleic apoptosis and cycle arrest at S and G2/M phases exhibiting several typical characteristics, cell shrinkage, lost cell contact, and apoptotic body formation. Moreover, putative compounds detected at 280 nm in the healthy SML were obviously higher than those in the bleached one, probably they could be bioactive molecules responsible for competitively exclusion of pathogens, Algicola and Vibrio, from the healthy SML.

Uncovering Metabolic Alterations in HCT-116 Colon Cancer Cells upon Exposure to Bamboo Leaf Extract Obtained from Guadua incana Londoño.

Metabolic alterations are increasingly recognized as important aspects of colorectal cancer (CRC), offering potential avenues for identifying therapeutic targets. Previous studies have demonstrated the cytotoxic potential of bamboo leaf extract obtained from Guadua incana (BLEGI) against HCT-116 colon cancer cells. However, the altered metabolic pathways in these tumor cells remain unknown. Therefore, this study aimed to employ an untargeted metabolomic approach to reveal the metabolic alterations of the endometabolome and exometabolome of HCT-116 cells upon exposure to BLEGI treatment. First, a chemical characterization of the BLEGI was conducted through liquid chromatography coupled with mass spectrometry (LC-MS). Next, we assessed cell viability via MTT and morphological analysis using an immunofluorescence assay against colon cancer cells, and anti-inflammatory activity using an LPS-stimulated macrophage model. Subsequently, we employed LC-MS and proton nuclear magnetic resonance (1H-NMR) to investigate intra- and extracellular changes. Chemical characterization primarily revealed the presence of compounds with a flavone glycoside scaffold. Immunofluorescence analysis showed condensed chromatin and subsequent formation of apoptotic bodies, suggesting cell death by apoptosis. The results of the metabolomic analysis showed 98 differential metabolites, involved in glutathione, tricarboxylic acid cycle, and lipoic acid metabolism, among others. Additionally, BLEGI demonstrated significant nitric oxide (NO) inhibitory capacity in macrophage cells. This study enhances our understanding of BLEGI's possible mechanism of action and provides fresh insights into therapeutic targets for treating this disease.

GuiErBai: a potent inhibitor, exhibiting broadly antitumor effect against cervical cancer in vitro and in vivo.

Introduction: Cervical cancer (CC) ranks as the fourth most prevalent malignant tumor among women worldwide, and is the fourth leading cause of cancer-related mortality. GuiErBai (GEB), a compound preparation developed by our research team, is derived from the ancient Chinese medicine of the Miao nationality and is comprised of podophyllotoxin (PTOX), imperatorin, isoimperatorin, and A. dahurica alkaloids. These individual components have demonstrated notable efficacy in tumor treatment. However, the specific anti-tumor effect of the compound Chinese medicine GEB in the context of CC has yet to be validated. Methods: HeLa and SiHa cell lines were utilized for in vitro experiments and treated with 5mg/mL and 10mg/mL GEB concentrations, respectively. The cell cycle changes after GEB treatment were assessed using flow cytometry. Transmission electron microscopy was employed to observe autophagic bodies and apoptotic bodies, while MDC staining evaluated the occurrence of autophagy. CCK-8 was used to observe the effect of GEB on cell proliferation, and Transwell assays assessed cell migration and invasion. Western blotting detected cell cycle and apoptosis-related protein expression, along with the expression level of autophagy-related protein LC3I/II. Changes in ROS and mitochondrial membrane potential in cervical cancer cells following GEB treatment were determined using ROS detection and mitochondrial membrane potential detection kits. For the in vivo experiment, a nude mouse model of cervical cancer transplantation based on HeLa cells was established. Experimental animals were divided into negative control, positive control, high-dose GEB (10mg/mL), and low-dose GEB (5mg/mL) groups. Results: In HeLa and SiHa cell lines, the G0/G1 phase of tumor cells significantly decreased (p < 0.001), while the G2/M phase increased notably (p < 0.001) following various GEB treatments. Electron microscopy showed GEB promoted apoptotic body and autophagosome formation in both cell lines. Compared to untreated HeLa and SiHa cells, GEB-treated cells exhibited significantly reduced caspase3 protein expression, and substantially increased autophagy-related protein LC3I/II expression. GEB treatment significantly reduced migration and invasion capabilities in both cell lines (p < 0.001), while ROS content and mitochondrial membrane potential were significantly elevated (p < 0.001). GEB effectively inhibited cervical cancer cell proliferation, with the optimal concentration being 10mg/mL. A successful nude mouse model of cervical cancer transplantation was established using HeLa cells. Post-GEB treatment, the tumor volume and weight in nude mice significantly decreased (p < 0.001), with diminished expression of CD34, VEGF, and caspase3 proteins in tumor tissues. Discussion: GEB exhibits a robust antitumor effect against cervical cancer, both in vitro and in vivo, in a concentration-dependent manner, by regulating autophagy and apoptosis of tumor cells.

An exploratory study on the effect of kynurenine metabolites on sEnd-2 endothelioma cells.

Cancer is the second leading cause of mortality worldwide. The development of anticancer therapy plays a crucial role in mitigating tumour progression and metastasis. Epithelioid hemangioendothelioma is a very rare cancer, however, with a high systemic involvement. Kynurenine metabolites which includel-kynurenine, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid have been shown to inhibit T-cell proliferation resulting in a decrease in cell growth of natural killercells and T cells. Furthermore, metabolites such as l-kynurenine have been shown to inhibit proliferation of melanoma cells in vitro. Considering these metabolite properties, the present study aimed to explore the in vitro effects of l-kynurenine, quinolinic acid and kynurenic acid on endothelioma sEnd-2 cells and on endothelial (EA. hy926 cells) (control cell line). The in vitro effect at 24, 48, and 72 h exposure to a range of 1-4 mM of the respective kynurenine metabolites on the two cell lines in terms of cell morphology, cell cycle progression and induction of apoptosis was assessed. The half inhibitory concentration (IC50), as determined using nonlinear regression, for l-kynurenine, quinolinic acid and kynurenic acid was 9.17, 15.56, and 535.40 mM, respectively. Optical transmitted light differential interference contrast and hematoxylin and eosin staining revealed cells blocked in metaphase, formation of apoptotic bodies and compromised cell density in l-kynurenine-treated cells. A statistically significant increase in the number of cells present in the sub-G1 phase was observed in l-kynurenine-treated sample. To our knowledge, this was the first in vitro study conducted to investigate the mechanism of action of kynurenine metabolites on endothelioma sEnd-2 cells. It can be concluded that l-kynurenine exerts an antiproliferative effect on the endothelioma sEnd-2 cell line by decreasing cell growth and proliferation as well as a metaphase block. These hallmarks suggest cell death via apoptosis. Further research will be conducted on l-kynurenine to assess the effect on cell adhesion in vitro and in vivo as cell-cell adhesion has been shown to increase metastasis to distant organs therefore, the inhibition of adhesion may lead to a decrease in metastasis.

Organoruthenium metallocycle induced mutation in gld-1 tumor suppression gene in JK1466 strain and appreciable lifespan expansion

Four Ru(II) complexes (A2-A5) were synthesized from the reaction of coumarin Schiff base ligands (7da2-tsc, 7da3-mtsc, 7da4-etsc and 7da5-ptsc) with [RuHCl(CO)(PPh3)3]. The compounds were characterized by FT-IR, UV–Vis, 1H, 13C and 31P NMR, mass spectrometry and crystallographic analysis. Calf Thymus DNA (CT-DNA) binding studies revealed the intercalative mode of binding of the complexes with DNA. The results of Bovine serum albumin (BSA) binding studies established the interaction between BSA followed static quenching mechanism. The cytotoxic effects of the complexes and the ligands were evaluated against breast (MCF-7 and MDA-MB-231) and lung carcinoma cell lines (A549 and NCI-H460) using MTT assay. Complex A4 demonstrated potent cytotoxic effects on both breast and lung cancer cells. Furthermore, morphological observations and FACS analysis showed the decrease in cell density by complex A4 by induced morphological changes and apoptotic body formation and cell death in both breast and lung cancer cells. Moreover, the invertebrate model Caenorhabditis elegans was employed to assess the in vivo anticancer activity of compound A4. The findings indicated that the treatment with A4 reduced tumor development and significantly extended organismal lifespan by 64 % in the tumoral strain JK1466 without adversely affecting essential physiological functions of the worm. Additionally, A4 demonstrated an upregulation of two crucial antioxidant defense genes. Overall, these results suggested that the compound A4 can be a potential candidate with novel chemotherapeutic applications.

The In Vitro Effect of Kynurenine Metabolites on Cell morphology, Cell cycle progression and the Induction of Apoptosis in Tumour Endothelioma Cells

Background: Cancer is one of the leading causes of death worldwide. The development of anticancer therapies plays a crucial role in mitigating tumour progression and metastasis. Kynurenine metabolites which include L-kynurenine, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid have been shown to inhibit T-cell proliferation resulting in a decrease in cell growth of natural killer (NK) cells and T cells. Research showed that L-kynurenine inhibits proliferation of melanoma cells in vitro. Methods: The present study aimed to explore the in vitro influence of L-kynurenine, quinolinic acid and kynurenic acid on endothelioma sEnd-2 cells at concentration ranges of 1 mM – 4 mM for 24 h, 48 h and 72 h on cell morphology, cell cycle progression and induction of apoptosis. Results and Discussion: The half inhibitory concentration (IC50), as determined using GraphPad Prism, for L-kynurenine, quinolinic acid and kynurenic acid was 10.77 mM, 14.78 mM and 535.40 mM respectively. Optical transmitted light differential interference contrast and hematoxylin and eosin staining revealed the presence of cells blocked in metaphase, formation of apoptotic bodies and compromised cell density in L-kynurenine- and quinolinic acid- treated cells. A statistically significant increase in the number of cells present in the sub-G1 phase was observed in L-kynurenine-treated samples. Conclusion: It can be concluded that L-kynurenine exerts an antiproliferative effect on the sEnd-2 cell line by a decrease in cell growth and proliferation and metaphase block. These hallmarks suggest cell death via apoptosis. Further research will be conducted on L-kynurenine to assess the effect on cell adhesion in vitro and in vivo. This research was supported by the following grants: The Research Development Programme at the University of Pretoria awarded to Dr YN Hlophe; National Research Foundation awarded to Dr YN Hlophe (A1F4685 &amp; N1F580); The University Capacity Development Programme (UCDP) awarded to Ms Tatchum (A1D783 &amp; N1F120). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Caspase-resistant ROCK1 expression prolongs survival of Eµ-Myc B cell lymphoma mice.

Apoptosis is characterized by membrane blebbing and apoptotic body formation. Caspase cleavage of ROCK1 generates an active fragment that promotes actin-myosin-mediated contraction and membrane blebbing during apoptosis. Expression of caspase-resistant non-cleavable ROCK1 (Rock1 NC) prolonged survival of mice that rapidly develop B cell lymphomas due to Eµ-Myc transgene expression. Eµ-Myc; Rock1 NC mice had significantly fewer bone marrow cells relative to those in Eµ-Myc mice expressing wild-type ROCK1 (Rock1 WT), which was associated with altered cell cycle profiles. Circulating macrophage numbers were lower in Eµ-Myc; Rock1 NC mice, but there were higher levels of bone marrow macrophages, consistent with spontaneous cell death in Eµ-Myc; Rock1 NC mouse bone marrows being more inflammatory. Rock1 WT recipient mice transplanted with pre-neoplastic Eµ-Myc; Rock1 NC bone marrow cells survived longer than mice transplanted with Eµ-Myc; Rock1 WT cells, indicating that the survival benefit was intrinsic to the Eµ-Myc; Rock1 NC bone marrow cells. The results suggest that the apoptotic death of Eµ-Myc; Rock1 NC cells generates a proliferation-suppressive microenvironment in bone marrows that reduces cell numbers and prolongs B cell lymphoma mouse survival.

Cytotoxic activity and mechanism of action of Smp43 scorpion peptide against colorectal cancer cell line HCT-116

This study was conducted to extend our previous investigations to examine the cytotoxic efficacy of Smp43 scorpion peptide against colorectal cancer cell line (HCT-116) and revealing its molecular mechanisms of action. Using MTT assay, Smp43 significantly induced cytotoxic effects on HCT-116 cancer cells compared to normal colon epithelial cell line (FHC) of IC50 4.11 and 62.17 µg/ml, respectively. Flow cytometric apoptosis assay showed that IC50 (4.11 µg/ml) of Smp43 induced a remarkable increase in the proportion of HCT-116 cancer cells undergoing late apoptotic cell death. Also, Smp43 caused cell cycle arrest at the S phase. RT-PCR analysis showed highly significant downregulation of Bcl-2 anti-apoptotic gene and ki-67 proliferative markers in HCT-116 treated with IC50 of Smp43. In contrast, caspase-3, −8, −9, Bax, and p53 apoptotic genes were upregulated. Protein expression levels of caspase-3, −8, −9, and p53 were similarly elevated in treated cells using a western blot analysis. The apoptotic characteristics were also confirmed through scanning and transmission electron microscopy. The Smp43 treated HCT-116 cancer cells showed cell membrane blebbing, pore formation, heterochromatin condensation toward the nuclear envelope, leakage of cell organelles, and formation of apoptotic bodies. Consequently, Smp43 peptide provides a great starting point for creating effective cytotoxic agents against human colorectal cancer.

Synthesis, characterization, DFT calculations, and anticancer properties of VI-period and f-block elements-substituted zinc oxide nanopowders

Nanotechnology provides promising ways in which a wide range of new materials can be manufactured which appear to have enormous potential in the field of biomedicine and life sciences. ZnO can be applied in many physical and optical processes and used as a good anti-cancer agent. ZnO NPs are recognized as SAFE or GRAS, non-toxic and biocompatible particles. In this study, wurtzite ZnO samples co-doped by rare earth elements (Tb, Er) were prepared via sol-gel auto-combustion route and their crystallographic structure as well as their morphologies were examined using XRD and TEM techniques. The analysis disclosed that all synthesized products crystallized in a hexagonal structure and the crystallites/particles size diminished with the increase of co-doping content. The electronic structure and optical properties of the different products were assessed using DFT calculations. Doping Tb and Er rare earth elements into ZnO has a significant effect on its optoelectronic properties. The computational study showed that the co-doping of Tb and Er on pure ZnO decreased the band gap and increased the refractive index. The extinction spectrum of pristine ZnO showed a peak in the ultraviolet region at 5 eV, while those of the co-doped ZnO samples displayed stronger peaks in the infrared region (near 0.4 eV). The anticancer properties of Tb/Er co-doped ZnO nanoparticles were examined on cervical cancer (HeLa cells) and colon cancer (HCT-116) by using an in vitro MTT assay. The cell viability assay findings indicated a reduction in HeLa and HCT-116 cells after 48 h of treatment of the synthesized samples. The treatment with co-doped ZnO nanoparticles produced chromatin condensation and formation of apoptotic bodies in HCT-166 cells, which indicates that the prepared co-doped ZnO nanoparticles induced programmed cell death in HCT-116 cells. According to these results, it can be concluded that the prepared Tb/Er co-doped ZnO nanoparticles have promising applications in developing new optoelectronic devices and also in treating cervical and colon cancers.

Cyanine-induced apoptosis for cancer therapy

Apoptosis is a programmed cell death characterized by cell rounding, chromatin condensation and clumping, cytoplasmic collapse, and the formation of apoptotic bodies. Recently, increasing scientific research has disclosed the close relationship between apoptosis and cyanine. Cyanine, due to its excellent fluorescent characteristics, is used in constructing vital fluorescent cores for fluorescent probes. It has been extensively utilized in targeted labeling for growing cells and tumor phototherapy. Cyanine-derived compounds have provided new approaches for treating different cancers by inducing tumor cell apoptosis. This review introduces the molecular mechanism of apoptosis, essential apoptosis-related proteins, and the pathways related to tumor cell apoptosis. Furthermore, it systematically discusses the function of cyanine in cancer therapy by inducing apoptosis. A deeper understanding of cyanine-induced apoptosis may offer new options for cancer treatment and new strategies for developing and utilizing cyanine.

STUDY OF CHEMOPREVENTIVE ROLE OF PADDY HUSK ON CERVICAL ADENOCARCINOMA HUMAN CELL LINE (HELA CELLS)

Objective: Cervical cancer is the fourth most prevalent cancer type and the fourth primary cause of cancer-related death among women worldwide. The deficiencies of current treatments, including severe side effects and the inability to prevent progression to the metastatic stage, necessitate the investigation of alternative agents. Methods: The chemopreventive approach employing natural products such as Paddy Husk is acquiring considerable traction in the scientific community. This study examined the chemopreventive effects of Paddy Husk on HeLa cervical cancer cells. Using the TBEA method, the IC50 of the husk was determined. To evaluate the antiproliferative activity with prolonged treatment exposure, HeLa cells treated with the IC50 value were incubated for 8 days. Results: The results demonstrated that Paddy Husk extract effectively inhibited the proliferation of HeLa cells throughout the duration of the treatment. Examination under the microscope revealed that Paddy Husk extract induces apoptotic characteristics, including cell contraction, membrane rounding, membrane blebbing, the formation of apoptotic bodies, and vacuolation. A mouse skin fibroblast cell line (L929) was used to assess the in vitro safety of paddy refuse extracts at various concentrations, revealing no toxic effects on normal L929 cells. Conclusion: These findings are essential for advancing our knowledge and recognizing the potential function of Paddy Husk compounds in cervical cancer chemoprevention.

Eleutheroside B induces apoptosis and autophagy of lung cancer cells by regulating PI3K/Akt/mTOR pathway

This study investigated the effect of eleutheroside B on apoptosis and autophagy of lung cancer A549 and H460 cells and its molecular mechanism. MTT assay was used to detect the cytotoxicity of eleutheroside B at 5, 10, 15, 20, 25, 30, 35, 40, and 45 mmol·L~(-1) on lung cancer cells. Trypan blue exclusion assay was used to detect the effect of eleutheroside B on the survival rate of lung cancer A549 and H460 cells at different time. Colony formation assay was used to detect the effect of eleutheroside B on the proliferation of lung cancer A549 and H460 cells. AO/EB fluorescence double staining and Hoechst 33342 fluorescence staining were used to detect the effect of eleutheroside B on apoptosis of lung cancer A549 and H460 cells, and Western blot was used to detect apoptosis-related proteins to explore the apoptosis-related molecular mechanism. AO fluorescence staining and Western blot were used to detect the expression of autophagic vesicles and autophagy-related proteins P62 and LC3. The results showed that compared with the control group, eleutheroside B inhibited the growth of lung cancer A549 and H460 cells in a concentration-dependent manner. The optimal effect time of eleutheroside B on lung cancer A549 and H460 cells was 24 h, and the optimal concentrations were 28.64 and 22.16 mmol·L~(-1), respectively. Eleutheroside B could inhibit the colony formation of A549 and H460 cells. Compared with the control group, eleutheroside B could promote the formation of apoptotic bodies and induce cell apoptosis, as well as induce the expression of mitochondrial pathway-related proteins. Under the effect of eleutheroside B, the acidic autophagy vacuole in lung cancer cells increased, LC3Ⅱ expression increased, P62 protein expression decreased, and PI3K, p-Akt, and p-mTOR protein expression decreased in the PI3K/Akt/mTOR pathway. Studies have shown that eleutheroside B can inhibit the growth of lung cancer cells, reduce colony formation, induce apoptosis of lung cancer cells through mitochondrial pathway, and induce autophagy. The mechanism may be related to the PI3K/Akt/mTOR pathway.

Assessment of the in vitro Antimelanoma Potential of Lippia microphylla Cham (Verbenaceae) Essential Oil.

Essential oils stand out among natural products for their complex composition, frequently described in the literature with a range of biological effects. This study evaluated the cytotoxic activity against several human cancer cell lines of essential oils extracted from the leaves of Lippia microphylla (EO-LM) Cham. (Verbenaceae). The melanoma cell line SK-MEL-28 was the most sensitive to the EO-LM, presenting an IC50 of 33.38 ± 1.16 µg/mL. Afterward, the effects of EO-LM on the cell cycle, induction of apoptosis, and production of reactive oxygen species (ROS) were evaluated. We stated a significant increase in the sub-G1 population, indicating apoptosis, later confirmed by an increase of SK-MEL-28 cells labeled with Annexin V-FITC and by the formation of apoptotic bodies and membrane blebs, observed by confocal microscopy. Additionally, EO-LM reduced the production of ROS, indicating antioxidant activity. Therefore, EO-LM exhibits anti-melanoma activity in vitro, suggesting its potential as an anticancer agent.