Extract Inhibits Cell Proliferation Research Articles

Kalanchoe pinnata (Lam.) Pers. Leaf ethanolic extract exerts selective anticancer activity through ROS-induced apoptotic cell death in human cancer cell lines

BackgroundThe leaves of Kalanchoe pinnata (Lam.) Pers. (K. pinnata), a succulent plant native to tropical regions, are used as a medicinal alternative against cancer in several countries worldwide; however, its therapeutic potential to fight cancer has been little addressed. In this study, we analyzed the phytochemical content, antioxidant capacity, and selectivity of K. pinnata leaf ethanolic extract against different human cancer cell lines in vitro.MethodologyThis study subjected the ethanolic extract to enzymatic assays to quantify the phytochemical content (phenolics, flavonoids, and anthraquinones) and its radical scavenging and iron-reducing capacities. Also, the phytoconstituents and major phenolic compounds present in the extract’s subfractions were identified by GC-MS, HPLC, and NMR. Human cancer (MCF-7, PC-3, HT-29) and normal colon (CoN) cell lines were treated with different concentrations of K. pinnata leaf ethanolic extract, and the changes in cell proliferation (sulforhodamine B assay), caspases activity (FITC-VAD-FMK reporter), mitochondrial membrane potential (MMP, rhodamine 123 assay), chromatin condensation/fragmentation (Hoechst 33342 stain), and ROS generation (DCFH2 probe assay) were assessed.ResultsThe results showed that the K. pinnata leaf ethanolic extract is rich in phytoconstituents with therapeutic potential, including phenols (quercetin and kaempferol), flavonoids, fatty acid esters (34.6% of the total composition), 1- triacontanol and sterols (ergosterol and stigmasterol, 15.4% of the total composition); however, it presents a poor content of antioxidant molecules (IC50 = 27.6 mg/mL for H2O2 scavenging activity vs. 2.86 mg/mL in the case of Trolox). Notably, the extract inhibited cell proliferation and reduced MMP in all human cell lines tested but showed selectivity for HT-29 colon cancer cells compared to CoN normal cells (SI = 8.4). Furthermore, ROS generation, caspase activity, and chromatin condensation/fragmentation were augmented significantly in cancer-derived cell lines, indicating a selective cytotoxic effect.ConclusionThese findings reveal that the K. pinnata leaf ethanolic extract contains several bioactive molecules with therapeutic potential, capable of displaying selective cytotoxicity in different human cancer cell lines.

Evaluation the Anti-leukemia effect of Methanol extracts of Camellia cuongiana on the K562 cell line

This study aims to examine the anti-proliferation effects of Camellia cuongiana methanolic extracts on the K562 chronic myelogenous leukaemia cell line. The crude extract was obtained by soaking the sample with methanol, following concentration using a rotary evaporator. Trypan blue exclusion test was performed in five concentrations of extract to detect the anti-cancer characteristic of Camellia cuongiana. Morphological changes in the treatment cell were observed using a phase-contrast microscope. After 72 hours of treatment, the extracts inhibited cell proliferation, with IC50 values of 72.26±5.75µg/mL. Increasing the extract concentration decreased the number of living cells. The most frequently observed abnormal morphology was cell shrinkage. Evidently, Camellia cuongiana could inhibit cancer cell proliferation and induce programmed cell death.

Phytochemical characterization by GC-MS and in vitro evaluation of antiproliferative and antimigratory studies of Leucas aspera leaf extracts on MDA-MB-231 cell line.

Breast cancer is the most recurrently identified and one of women's prominent causes of death. Currently, researchers have turned their focus on natural chemicals from synthetic chemicals due to their environmental, economic, and health benefits. Considering this, the medicinal plant Leucas aspera was chosen for the current study. The aim of this study was to isolate and characterize secondary metabolites from L. aspera and determine the antiproliferative and antimigratory activities in the MDA-MB-231 cell line under in vitro conditions. Phytochemicals from L. aspera were isolated through sequential extraction using hexane, dichloromethane, and ethyl acetate. These extracts were qualitatively screened, subjected to FT-IR, and analyzed using GC-MS. The antiproliferative activity was determined through the MTT assay. Scratch assay was utilized to determine the antimigratory activity of the plant extracts. The phytochemical analysis revealed the presence of steroids, alkaloids, phenols, flavonoids, galactose, tannins, saponins, and amino acids in the extracts. The results of the cell viability assay indicated that the crude dichloromethane and ethyl acetate extracts inhibited cell proliferation, with inhibitory concentrations of 5 and 3 μg/ml, respectively. In contrast, the crude hexane extract did not exhibit any cytotoxicity. Furthermore, the scratch assay results showed that the plant extracts had cell migration inhibitory properties. The outcomes of the current study conclude that L. aspera possesses active therapeutic agents with strong anticancer potential, effectively impeding the proliferation and invasion of MDA-MB-231. Further studies are needed to identify the potential active agents that contribute to these activities.

Ardisia gigantifolia ethanolic extract inhibits cell proliferation and targets cancer stem cells in gastric cancer

Objective: To evaluate the effects of ethanol extract from Ardisia gigantifolia leaves on cell proliferation and cancer stem cell (CSC) number in gastric cancer. Methods: The inhibitory effect of Ardisia gigantifolia extract on the proliferation of MKN45 and MKN74 gastric cancer cells was assessed using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay. Non-adherent culture (3D) model was used to evaluate the effect of the extract on tumorsphere size and number. Moreover, the expression of CD44, ALDH, and p21 was determined by immunofluorescence analysis. Flow cytometric analysis was performed to evaluate cell cycle arrest and the expression of gastric CSC markers CD44 and ALDH. Real-time PCR analysis was also carried out to assess the effect of the extract on the expression of cell cycle-regulated genes. Results: Ardisia gigantifolia extract effectively inhibited cell proliferation with an IC50 of 55.7 µg/mL in MKN45 cells and 123.6 µg/mL in MKN74 cells. The extract also arrested cell cycle in the G0/G1 phase as well as significantly reduced the size and number of tumorspheres. The markedly increased expression of p21 was observed at both mRNA and protein levels in the extract-treated adherent cells and tumorspheres. In addition, Ardisia gigantifolia extract significantly reduced the number of CD44- and/or ALDH-expressing gastric CSC. Conclusions: The development of gastric CSC can be inhibited by the ethanol extract of Ardisia gigantifolia.

Biological behavior of the extract of green walnut husks on gastric cancer MGC80-3 cells

Stomach cancer (SC) is a relatively common cancer in my country, with a high mortality rate, which seriously threatens our health. This article studied the effect of Green walnut husks (GWH) extract on the biological behaviors and NF-κB protein levels of gastric cancer MGC80-3 cells, and provided evidence and support for the research and treatment of gastric cancer. Cell proliferation was measured by Thiazole blue and apoptosis by flow cytometry. Cell migration was analyzed by scratch experiment and the levels of NF-κB, NF-κBp65 and COX-2 in MGC80-3 cells were examined by Western blot and QRC-PCR. It was found that GWH extract inhibited cell proliferation and increased apoptosis. GWH extract significantly downregulated NF-κB, NF-κBp65 and COX-2. The growth process of cancer cells is related to biological behaviors such as cell proliferation and apoptosis. By inhibiting the biological behavior of cancer cells, inhibitory proteins can effectively inhibit gastric cancer. In summary, GWH extract has a great influence on gastric cancer MGC80-3 cells and the NF-κB protein expression.

Antiproliferative Effects of Methanolic Root Extracts of Eichhornia crassipes Against a Skin Melanoma Cell Line: An In Vitro Study.

Background Melanoma is the most aggressive form of skin cancer, accounting for 3% of all malignant cancers. Phytochemicals and their related compounds are found in various parts of the plant Eichhorniacrassipes and have a variety of pharmacological actions. The current research was intended to compare and evaluate the anti-proliferative action of methanolic extracts of E. crassipes roots and petioles against the Sloan Kettering Melanoma (SK-Mel-5) cell line. Materials and methods The waters around Ezhikkara, Ernakulum, Kerala, were discovered to contain E. crassipes. We used a Soxhlet extractor to get this concentrated liquid. For this test, we employed a methanolic extract of roots and petioles to determine the extent to which different concentrations of the extract inhibited cell proliferation. Data on absorbance were reported as a mean standard deviation. Using Probit analysis, the IC50 was calculated by evaluating the gradient of the regression line to get a value. Results Concentrations of methanolic root and petiole extracts of 12.5 µg/ml, 25 µg/ml, 50 µg/ml, 100 µg/ml, and 200 µg/ml were analyzed. The methanol petiole extract reduced the viability of SK-Mel-5 cells more than the root extract, with IC50 values of 323.59 µg/ml and 174.70 µg/ml of the test sample concentration, respectively. The regression equation for the root extract was y = -0.1264x + 90.902 and R2 = 0.845, and for the petiole extract, it was y = -0.2187x + 88.206 and R2 = 0.917. Conclusion The current study found that increasing the concentration of methanolic extracts of roots and petioles of E. crassipes exhibited an increased cell growth inhibition rate. However, methanolic petiole extracts were more cytotoxic than the roots. Thus, the current study demonstrated the therapeutic use of E. crassipes as an anticancer agent, thereby providing a valuable alternative for enabling the early management of melanoma.

Alisma orientale extract inhibits cell proliferation by promoting oxidative stress and apoptosis in prostate cancer cells

Prostate cancer is a prevalent malignancy in men, necessitating the development of more effective treatment drugs. Alisma is commonly used in clinical settings for various ailments, including tumors. However, its mechanism of action in prostate cancer cells remains unclear. This study aimed to clarify the effects of Alisma orientale extract (AOE) on prostate cancer. Our results showed that AOE inhibited prostate cancer cell growth and induced apoptosis while promoting oxidative stress. Mechanistically, AOE modulated the p38/nuclear factor kappa-B (NF-κB) pathway to inhibit prostate cancer progression. Taken together, these findings suggest that AOE could serve as a potential treatment for prostate cancer.

Antiproliferative Effects of the Methanolic Petiole Extract of Eichhornia crassipes Against Sloan Kettering Melanoma 5 Cell Line: An In Vitro Study.

Background Eichhornia crassipes (E. crassipes) have several secondary metabolites that have medicinal value. These include sterols, alkaloids, phenolics, flavonoids, tannins, and saponins. In the current study, the methanolic petiole extract of E. crassipeswas examined to determine its potential antiproliferative activity against Sloan Kettering Melanoma 5 (SK-Mel-5) cell lines. Materials and methods Eichhorniacrassipeswere obtained from the water bodies of Ezhikkara, Ernakulam, Kerala. The Soxhlet technique was used to produce the extract. Leaves, petioles, and roots were dried and pulverized before being analyzed phytochemically in a number of solvents. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to measure the extent to which various dosages of the extract inhibited cell proliferation, and the methanolic extract of petioles was chosen since it contained more anticancer components. The half maximal inhibitory concentration (IC50) was determined by utilizing a probit model and the slope-gradient method of the regression equation. The Statistical Package for Social Sciences (SPSS) version 21 (IBM SPSS Statistics, Armonk, NY) was used for the analysis. Results We examined the effects of 12.5, 25, 50, 100, and 200 μg/ml of methanolic petiole extract. The data indicated that the methanol extract significantly reduced SK-Mel-5 cell viability. Cell growth inhibition increased with concentration but was shown to be relatively low at 100 g/ml, exhibiting 38.911% of inhibitory activity. The percentage of cell growth inhibition at 200 g/ml was 52.965%. The methanolic petiole extracts of E. crassipes were found to be cytotoxic with IC50 values of 172.186 g/ml. Probit analysis was performed to obtain the regression equation. Conclusion The in vitro study suggests that the methanol extract of the petiole ofE. crassipeshad modest antiproliferative action against SK-Mel-5 cells, a typical human melanocyte tumor cell line. The study findings shed light on the anticancer activity of E. crassipes, making it an appropriate source of drug-lead chemicals for the development of safer and cost-effective remedies for cutaneous ailments varying from rashes to awful melanoma.

Efficacy of Trevesia palmata (Roxb. ex Lindl.) Vis. Extract on MG 63 cell lines and arthritis-induced animal models

Ethnopharmacological relevanceDespite widespread use of herbal remedies for treating arthritis and osteosarcoma, many plants are still not pharmacologically evaluated for their efficacy. Contrary to many non-steroidal, immunosuppressants, antibiotics, and antineoplastic drugs that have adverse effects, phytotherapeutic compounds have promising benefits with fewer complications. In this study the unexplored Northeastern India indigenous plant Trevesia palmata (Roxb. ex Lindl.) Vis. used in traditional medicine to cure bone fractures is chosen for studying anti-proliferative and anti-rheumatic properties. Aim of the studyThis study designed to explore the polyphenolic composition, antioxidant, anti-inflammatory and anti-arthritic potential of T. palmata leaf extracts. Further, the cellular activity was studied using MG 63 osteoblast cell lines and pharmacologically evaluated using Complete Freund's Adjuvant (CFA) induced arthritic rat model. Materials and methodsIn vitro free radical scavenging activity, anti-inflammatory and anti-arthritic activities of extracts were analyzed using standardized methods. The polyphenolic profiling and apoptosis inducing ability of T. palmata ethyl acetate (TPEA) extract on MG 63 osteoblast cell lines were analyzed. The in vivo pharmacological studies were carried out with low dose 250 mg/kg and high dose of 500 mg/kg of T. palmata. The biochemical and haematological parameters and in vivo antioxidant activity were evaluated for the control and treated groups. Radiological and histological study were done to understand the impact and penetration of inflammatory arthritis from tissues to joint bones. ResultsTPEA showed highest free radical scavenging activity (DPPH - 4.72 IC50, ABTS - 242.33 ± 6.81 mM TE/g extract), anti-inflammatory (40.04% inhibition of RBC lysis) and anti-arthritic activity (32.4% inhibition of protein denaturation) with the presence of gallic acid, catechin, caffeic acid, rutin, quercetin and naringenin. The TPEA extract inhibited cell proliferation of MG 63 osteoblast cells and induced apoptosis by arresting cell cycle at different phases. After acute toxicity studies the doses 250 mg/kg and 500 mg/kg were fixed and showed better results in CFA-induced arthritic animals. Thus, the extract phytoconstituents may have immense potential against chronic inflammation, joint ailments, bone cancer and arthritis which serves as a phytomedicine contrary to synthetic medications. ConclusionsThe potential treatment of polyphenolic compounds in the T. palmata extract on osteosarcoma and arthritis was demonstrated from this study. Thus, cellular inflammatory infiltrates are significantly reduced in bone and joint tissues as well.

Antiproliferative activity of Andrographis paniculata seed extracts on hepatocellular carcinoma cells

Leading cause of death world side is because of severe health problems due to cancer. Compounds occurring naturally from plants known as phytochemical are rich sources of anticancer drug development, in depth screening assessments are necessary. The objective of the present study aimed to investigate the mechanistic pathway of antiproliferative activity of ethanolic Andrographis paniculata seed extract against Hepatocellular carcinoma cell (HepG2) cell line. Cell cycle arrest and apoptosis study was performed by Flow cytometry analysis. The expression of certain apoptosis gene associated with cell cycle regulation was conducted by QRT-PCR assay to assess the effect of ethanolic Andrographis paniculata seed extract on HepG2 cells. Andrographis paniculata seed extract inhibited cell proliferation and arrest proliferation on HepG2 cells at G2/M phase when compared to untreated cells. The ethanol extract of Andrographis paniculata seed found to be active cell inhibitor at the time and dose dependent manner. The QRT-PCR assay report reveals that pro-apoptotic genes BCL2 Associated X (BAX), Caspase-3, Caspase-8 genes on both treated and untreated cells. B-cell lymphoma 2 (Bcl-2) is down regulated in treated groups compared to untreated group and Beta actin was used as internal control.

The Suppressive Activity of Water Mimosa Extract on Human Gastric Cancer Cells

Epidemiological studies have evidenced that natural dietary products can prevent or manage gastric cancer. Neptunia oleracea, an aquatic vegetable and edible plant, has been reported to have anti-cancer properties. In this study, N. oleracea extract’s suppression of gastric cancer cells was investigated on an in vitro experimental model. We found that ethyl acetate (EtOAc) extract inhibited cell proliferation at IC50 value of 172 µg/mL. Moreover, the treatment of EtOAc extract at a concentration of 50 µg/mL for 24 h caused suppression of cancer cell migration. Notably, a real-time PCR assay revealed that EtOAc extract induced the process of apoptosis via upregulating the mRNA expression level of caspase-8, Bax, caspase-9, and caspase-3 in cancer cells. In conclusion, N. oleracea had potential anti-cancer activity against gastric cancer cells, suggesting its role in the prevention and management of gastric cancer.

Piper betle stem extract induces apoptosis through mitochondria inactivation, p38MAPK activation and ErB2/ErbB3 suppression on oral squamous cell carcinoma cells

BackgroundOral cancers are a group of carcinomas that appear in the oral cavity. The cause of oral cancer is still unclear. However, betel nut chewing, smoking and drinking alcohol are all known risk factors for oral cancers, among which the habit of chewing of betel nuts is known to be associated with the highest risk of oral cancer. Hypothesis/PurposeThis study aimed to examine the mechanisms of anti-cancer effects of the Piper betle (P. betle) stem. MethodsIn this study, MTT assays, cell morphology analysis and flow cytometry were employed to evaluate the anti-cancer effects of an extract of the P. betle stem on human oral squamous cell carcinoma cell lines Cal-27 and Ca9-22. Potential effects on cell proliferation and apoptotic molecular mechanisms were evaluated by western blotting. ResultsTreatment with P. betle stem extract inhibited cell proliferation in Cal-27 and Ca9-22 cells, and its effect on cell growth was mediated by a mechanism associated with apoptosis. The apoptotic cell death involved mitochondrial inactivation, causing downregulation of the expressions of Bcl-2 and Bcl-xl and increasing the expressions of Bax and Bad. Activation of p38MAPK and inhibition of the expressions of ErbB2 and ErbB3 were also involved in the P. betle stem extract-induced apoptosis in oral cancer cells. ConclusionThe findings from this study indicated that crude extract of the P. betle stem may regulate signaling pathways via apoptosis, suggesting that this extract has great potential for development as a new drug for the treatment of oral cancer.

Elaeagnus angustifolia Plant Extract Induces Apoptosis via P53 and Signal Transducer and Activator of Transcription 3 Signaling Pathways in Triple-Negative Breast Cancer Cells.

Elaeagnus angustifolia (EA) is used as an alternative medicine in the Middle East to manage numerous human diseases. We recently reported that EA flower extract inhibits cell proliferation and invasion of human oral and HER2-positive breast cancer cells. Nevertheless, the outcome of EA extract on triple-negative breast cancer (TNBC) cells has not been explored yet. We herein investigate the effect of the aqueous EA extract (100 and 200 μl/ml) on two TNBC cell lines (MDA-MB-231 and MDA-MB-436) for 48 h and explore its underlying molecular pathways. Our data revealed that EA extract suppresses cell proliferation by approximately 50% and alters cell-cycle progression of these two cancer cell lines. Additionally, EA extract induces cell apoptosis by 40–50%, accompanied by the upregulation of pro-apoptotic markers (Bax and cleaved caspase-8) and downregulation of the anti-apoptotic marker, Bcl-2. Moreover, EA extract inhibits colony formation compared to their matched control. More significantly, the molecular pathway analysis of EA-treated cells revealed that EA extract enhances p53 expression, while inhibiting the expression of total and phosphorylated Signal Transducer and Activator Of Transcription 3 (STAT3) in both cell lines, suggesting p53 and STAT3 are the main key players behind the biological events provoked by the extract in TNBC cells. Our findings implicate that EA flower extract may possess an important potential as an anticancer drug against TNBC.

Chemical characterization of non-psychoactive Cannabis sativa L. extracts, in vitro antiproliferative activity and induction of apoptosis in chronic myelogenous leukaemia cancer cells.

In this study, extracts from non‐psychoactive Cannabis sativa L. varieties were characterized by means of ultra high‐performance liquid chromatography coupled with high‐resolution mass spectrometry (UHPLC‐HRMS) and their antiproliferative activity was assessed in vitro. The human chronic myelogenous leukaemia cell line K562 was chosen to investigate the mechanism of cell death. The effect on the cell cycle and cell death was analysed by flow cytometry. Proteins related to apoptosis were studied by western blotting. Mechanical properties of cells were assessed using the Micropipette Aspiration Technique (MAT). The results indicated that the cannabidiol (CBD)‐rich extract inhibited cell proliferation of K562 cell line in a dose‐dependent manner and induced apoptosis via caspase 3 and 7 activation. A significant decrease in the mitochondrial membrane potential was detected, together with the release of cytochrome c into the cytosol. The main apoptotic markers were not involved in the mechanism of cell death. The extract was also able to modify the mechanical properties of cells. Thus, this hemp extract and its pure component CBD deserve further investigation for a possible application against myeloproliferative diseases, also in association with other anticancer drugs.

Quercus acutissima Carruth. root extract triggers apoptosis, autophagy and inhibits cell viability in breast cancer cells

Ethnopharmacological relevanceThe bark of Quercus acutissima Carruth. (QA) has long been used by Chinese people to treat noncancerous growths and cancerous ailments. It was traditionally used by Chinese folk to inhibit tumor proliferation in cancerous treatment, but the specific mechanism remain to be elucidated. Aim of the studyThis study investigated the anticancer activities of QA root extract and its regulatory pathways in two human breast cancer cell lines (MCF-7 and SUM159). Materials and methodsDried QA root barks were extracted by ethanol and used to treat human breast cancer MCF-7 and SUM159 cells with varying concentrations. The CCK-8 assay, Hoechst 33342 staining assay and wound healing assay were used to detect the cell proliferation, apoptotic cell morphology, and cell migration in each group, respectively. Caspase 3 activity assay kit was used to determine caspase 3 activity. Western blot was used to measure proteins expression level in apoptosis and autophagy pathways (Bcl-W, caspase 3, Beclin1, LC3 and Atg5). LC-MS was performed to determine the chemical components in QA root extract. ResultsCCK-8 assay showed that QA root extract significantly inhibited cell viability and proliferation in breast cancer cells by a concentration-dependent manner. Cell wound healing assay indicated that it had high suppression ability on cell migration both in MCF-7 and SUM159 cells. QA root extract treatment induced the morphological and nuclear structural changes in breast cancer cells including rounded appearance and shrunken nucleus with several nuclear body fragments. Western blot indicated that QA root extract induced mitochondria-mediated apoptosis by up-regulating caspase 3 and down-regulating Bcl-W. Moreover, QA root extract up-regulated Beclin1 and Atg5, and activated LC3 in two human breast cancer cell lines. LC-MS results showed that QA root extract contains high content of bioactive compounds like coumarins and derivatives, prenol lipids, flavonoids and tannins. ConclusionsQA root extract inhibited cell proliferation and migration in MCF-7 and SUM159 cells, and it also induced cell morphology changes and regulated mitochondria-mediated apoptotic cell death and autophagic cell death.

Leaf extract of Osbeckia octandra induces apoptosis in oral squamous cell carcinoma cells

BackgroundOsbeckia octandra is a plant endemic to Sri Lanka and is used in ethnomedicine for treating various diseases. However, the anti-cancer properties of O. octandra are yet to be fully investigated. In the present study, we evaluated the anti-cancer effects of O. octandra on oral cancer cells.MethodsHuman oral cancer cell lines (HSC2, YD10B, YD38, YD9, and YD32) were used in this study. BrdU incorporation, cell cycle and annexin-V/PI staining were all evaluated using flow cytometry to determine the extent to which O. octandra leaf extract inhibits cell proliferation and induces apoptosis. Cell viability and reactive oxygen species (ROS) were also measured in order to investigate the anti-cancer effects of O. octandra extracts. Western blotting was performed to detect cell cycle related protein such as cyclin d1 and cdk4, and to detect apoptosis-related proteins such as Bcl-2, Bcl-XL, Bax, Caspase-9, Cleaved caspase-3, Fas, Caspase-8, and Bid.ResultsLeaf extract of O. octandra reduced oral squamous cell carcinoma (OSCC) cell viability in a dose-dependent manner. Leaf extract of O. octandra has non-toxic in normal keratinocytes. Also, O. octandra extract interrupted the DNA replication via G1 phase arrests, and this effect was independent of ROS generation. In the apoptosis-related experiments, the population of annexin V-positive cells increased upon treatment with O. octandra extract. Furthermore, the expression of anti-apoptotic protein (Bcl-2 and Bcl-xL) was decreased, whereas the expression of cleaved caspase-3 protein was increased in O. octandra-treated OSCC cells.ConclusionsThe results suggest that a leaf extract of O. octandra inhibited the proliferation of OSCC cells through G1 phase arrest and interrupting DNA replication. The leaf extract of O. octandra could trigger the apoptotic response via caspase 3 activation in OSCC cells. These results suggest that O. octandra has the potential to be developed as an alternative medicine for treating OSCC.

Antrodia salmonea extract inhibits cell proliferation through regulating cell cycle arrest and apoptosis in prostate cancer cell lines.

Antrodia salmonea (AS) is a fungus, which belongs to a fungal family of Taiwanofungus salmoneus with the features of anti-oxidant, anti-inflammatory, and anticancer. Recent studies have shown that AS has anti-cancer functions in ovarian and breast cancer. However, the effects of AS on prostate cancer (PCa) proliferation remain unknown. Therefore, we investigated the role of AS in PCa proliferation through apoptosis, and cell cycle regulation in PCa cell lines. Our results showed that Antrodia salmonea extract (ASE) inhibited PCa cells growth with a dose-dependent manner. In addition, ASE decreased the anchorage-independent growth formation ability in PC3 cells. Moreover, ASE-induced cell growth inhibition in PCa cells (DU145, PC3) was correlated to decreased cell cycle-related proteins such as cyclin A/B and cyclin-dependent kinase CDK1/2/4, and increased cell cycle inhibitor proteins p21. Besides, ASE decreased the total protein level of epidermal growth factor receptor and its downstream signaling pathways Akt and Erk in both PCa cells. We found that apoptotic markers such as cleaved-PARP protein levels increased significantly in DU145 cells indicating ASE might induce apoptosis. In conclusion, our results suggest that ASE may have the ability to induce PCa cell death through regulating cell cycle arrest and apoptosis pathways.

Cytotoxicity of Medicinal Mushrooms Oudemansiella canarii and Ganoderma lucidum (Agaricomycetes) Against Hematologic Malignant Cells via Activation of Apoptosis-Related Markers.

Cancer is the second leading cause of death worldwide, and despite of the of the availability of the advanced chemical treatments, development of effective and safe alternatives derived from natural resources are still of high interest. Mushroom is one of the important resources of pharmacologically active cytotoxic compounds. In this paper, we report the cytotoxicity of ethanolic extracts of Oudemansiella canarii (Jungh.) Höhn. and Ganoderma lucidum (W. Curt.: Fr.) P. Karst. against nine hematologic malignant cells and describe their molecular mechanisms. Cell lines were exposed to varying concentrations of mushroom extracts for 48 h and the cell proliferation and apoptosis parameters were determined. Western blot analysis was performed to determine the extract-induced changes in the level of apoptosis-related proteins in cancer cell lines and patient-derived mononuclear cells. Results revealed that O. canarii and G. lucidum extracts exhibited cytotoxicity with IC50 values of 26.8-66.0 ppm and 48.1-78.4 ppm, respectively, in all the cancer cell lines used. Mushroom extracts inhibited cell proliferation by 57.3-72.5% (O. canarii) and 44.2-67.4% (G. lucidum), which correlates to the activation of apoptosis as indicated by increased annexin V positivity, cells in sub G0/G1 phase and production of reactive oxygen species, and decreased mitochondrial membrane potential. Western blot analysis showed increase in the level of apoptotic markers (cleaved PARP1, cleaved caspase 3 and phosphorylation of histone 2AX) and activation of the stress-activated protein kinase (SAPK/JNK) signaling pathway. The extract-activated apoptosis was also observed in mononuclear cells isolated from the peripheral blood of leukemia and lymphoma patients. In conclusion, activation of pro-apoptotic markers is one of the major mechanisms of the cytotoxicity of O. canarii and G. lucidum extracts against hematologic malignant cells.

Ginkgo biloba Extract Inhibited Cell Proliferation and Invasion by Stimulating TET2 Expression Through miR-29a in Colorectal Carcinoma Cells.

Ginkgo biloba extract (GBE) has antitumor and antioxidant properties, which play a role in regulating gene and protein expression. The ten-eleven translocation (TET) proteins have the ability to regulate epigenetic modifications. However, the abnormal expression of TET2 protein has also been demonstrated in cancer development. In the present study, we analyzed the effects of GBE administration on TET2 expression in human colorectal cancer (CRC). The Cancer Genome Atlas database suggested that the expression of TET2 was lost in CRC. To investigate the expression profiles of TET2, GBE was used to treat CRC cells. The results showed that GBE could increase the expression of TET2 and 5-hydroxymethylcytosine (5hmC). In addition, GBE inhibited cell growth and invasion in SW480 cells. Moreover, to confirm whether TET2 expression affected cell proliferation, apoptosis, migration, and invasion, TET2 was knocked down and a TET2-overexpressing vector was constructed in human CRC cells. The results showed that overexpression of TET2 induced cell proliferation and invasion. Bioinformatic analyses showed that TET2 is a target gene of microRNA-29a (miR-29a). Moreover, reduced expression of miR-29a and increased TET2 expression in CRC cells. GBE was also used to treat a tumor model in nude mice. Compared to the control group, tumor growth was inhibited, and there was increased expression of TET2 in the GBE-treatment group in vivo. In conclusion, these results indicated that GBE inhibited cell proliferation and invasion through TET2 protein expression regulated by miR-29a in the development of CRC.

Evaluation of the anticarcinogenic potential of the endophyte, Streptomyces sp. LRE541 isolated from Lilium davidii var. unicolor (Hoog) Cotton

BackgroundEndophytic actinomycetes, as emerging sources of bioactive metabolites, have been paid great attention over the years. Recent reports demonstrated that endophytic streptomycetes could yield compounds with potent anticancer properties that may be developed as chemotherapeutic drugs.ResultsHere, a total of 15 actinomycete-like isolates were obtained from the root tissues of Lilium davidii var. unicolor (Hoog) Cotton based on their morphological appearance, mycelia coloration and diffusible pigments. The preliminary screening of antagonistic capabilities of the 15 isolates showed that isolate LRE541 displayed antimicrobial activities against all of the seven tested pathogenic microorganisms. Further in vitro cytotoxicity test of the LRE541 extract revealed that this isolate possesses potent anticancer activities with IC50 values of 0.021, 0.2904, 1.484, 4.861, 6.986, 8.106, 10.87, 12.98, and 16.94 μg/mL against cancer cell lines RKO, 7901, HepG2, CAL-27, MCF-7, K562, Hela, SW1990, and A549, respectively. LRE541 was characterized and identified as belonging to the genus Streptomyces based on the 16S rRNA gene sequence analysis. It produced extensively branched red substrate and vivid pink aerial hyphae that changed into amaranth, with elliptic spores sessile to the aerial mycelia. To further explore the mechanism underlying the decrease of cancer cell viability following the LRE541 extract treatment, cell apoptosis and cell cycle arrest assays were conducted in two cancer cell lines, RKO and 7901. The result demonstrated that LRE541 extract inhibited cell proliferation of RKO and 7901 by causing cell cycle arrest both at the S phase and inducing apoptosis in a dose-dependent manner. The chemical profile of LRE541 extract performed by the UHPLC-MS/MS analysis revealed the presence of thirty-nine antitumor compounds in the extract. Further chemical investigation of the LRE541 extract led to the discovery of one prenylated indole diketopiperazine (DKP) alkaloid, elucidated as neoechinulin A, a known antitumor agent firstly detected in Streptomyces; two anthraquinones 4-deoxy-ε-pyrromycinone (1) and epsilon-pyrromycinone (2) both displaying anticancer activities against RKO, SW1990, A549, and HepG2 with IC50 values of 14.96 ± 2.6 − 20.42 ± 4.24 μg/mL for (1); 12.9 ± 2.13, 19.3 ± 4.32, 16.8 ± 0.75, and 18.6 ± 3.03 μg/mL for (2), respectively.ConclusionOur work evaluated the anticarcinogenic potential of the endophyte, Streptomyces sp. LRE541 and obtained one prenylated indole diketopiperazine alkaloid and two anthraquinones. Neoechinulin A, as a known antitumor agent, was identified for the first time in Streptomyces. Though previously found in Streptomyces, epsilon-pyrromycinone and 4-deoxy-ε-pyrromycinone were firstly shown to possess anticancer activities.Graphical