Antiproliferative Properties of Extracts from Stachys sieboldii MIQ

2020 ◽  
Vol 16 (3) ◽  
pp. 342-347
Author(s):  
Eun Na ◽  
Jung Woo Lee ◽  
Stefan Winkler ◽  
Sun Young Lim

Background: The objective of this study was to investigate the antiproliferative effect of Stachys sieboldii MIQ. extracts on cancer cell lines. Methods: Dried S. sieboldii MIQ. was extracted using acetone/methylene chloride (A+M) or methanol (MeOH), and then fractionated using n-hexane, 85% aq. methanol (MeOH), butanol (BuOH) and distilled water. The cytotoxic activity of S. sieboldii MIQ. against AGS human gastric, HT-29 human colon and HT-1080 fibroblast cancer cell lines was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay. Results: The A+M extract showed significantly higher inhibition of cell growth in all three cell lines compared to the MeOH extract (p < 0.05). All the extracts and fractions from S. sieboldii MIQ. decreased the growth of AGS cells, and the effect was concentration-dependent. Among the different fractions, the n-Hexane and 85% aq. MeOH fractions inhibited AGS cell growth by >50% at a concentration of 0.1 mg/mL (p < 0.05). All fractions inhibited the proliferation of HT-29 cancer cell lines (p < 0.05), showing >50% inhibition at a concentration of 0.25 mg/mL. The A+M extract inhibited the growth of the HT-1080 cancer cells by 60% at a concentration of 0.25 mg/mL. The n-Hexane and 85% aq. MeOH fractions showed the highest growth inhibitory effect on the HT-1080 cancer cells (p < 0.05), similar to that observed in the AGS cancer cells. Conclusion: Thus, the n-Hexane and 85% aq. MeOH fractions from S. sieboldii MIQ. likely contain bioactive compounds such as polyphenols and flavonoids that could prevent cancer proliferation. Further research is needed to isolate these important compounds from the extracts.

2021 ◽  
Author(s):  
Suneetha Nunna ◽  
Ying-Pei Huang ◽  
Mahdi Rasa ◽  
Krepelova Anna ◽  
Francesco Annunziata ◽  
...  

Abstract BackgroundColorectal cancer (CRC) is one of the most frequent and lethal cancers in the world. The current medical treatment for CRC primarily includes combination of multiple chemotherapeutic, targeted and/or immunotherapeutic drugs. However, these approaches are still not fully successful and cause numerous and severe side effects for the patient. Therefore, there is an urgent need to discover novel and cancer-selective drugs for CRC treatment. As many other natural compounds, a-Mangostin and Paeonol possess anti-cancer properties, but both of these compounds have low solubility and low membrane permeability.Methodsa-Mangostin and Paeonol derivatives were chemically synthesized to increase cytotoxicity versus cancer cell over non-transformed cells. The anticancer properties of these compounds were investigated on human colon cancer cell lines by employing cell viability, apoptosis and cell-cycle analyses. Transcriptome of cancer cells treated with natural compounds were also analyzed by total RNA-sequencing. Finally, we investigated their effects on human colon organoids derived from healthy and cancerous tissue of the same patient.ResultsWe found the two derivative compounds (a-Mangostin-1 (aMan1) and Paeonol-1 (Pae1)) more efficiently induced cytotoxicity in HCT116, HT-29, and SW48 colorectal cancer cell lines than the parental compounds. Both, aMan1 and Pae1 arrested HCT116 cells in G1 and HT-29 and SW48 cells in G2/M phase of the cell cycle. aMan1 and Pae1 induced selective transcriptional responses in CRC cells involving genes related to metabolic stress and DNA damage response signaling pathways. Both aMan1 and Pae1 induced apoptosis in human cancer cells and organoids derived from tumor tissue without affecting the viability of human non-cancer cells and intestinal organoids derived from healthy tissue.ConclusionsOur findings increase the knowledge about natural compound derivatives as anticancer compounds and open new research options on the derivation of lead compounds aimed to the development of novel CRC chemotherapeutic drugs that selectively target cancer, but not healthy cells.


1994 ◽  
Vol 266 (3) ◽  
pp. G459-G468 ◽  
Author(s):  
P. Singh ◽  
Z. Xu ◽  
B. Dai ◽  
S. Rajaraman ◽  
N. Rubin ◽  
...  

Gastrin is mitogenic for several colon cancers. To assess a possible autocrine role of gastrin in colon cancers, we examined human colon cancer cell lines for expression of gastrin mRNA and various forms of gastrin. Gastrin mRNA was not detected in the majority of colon cancer cell lines by Northern hybridization but was detected in all human colon cancer lines by the sensitive method of reverse transcriptase-polymerase chain reaction (PCR). Gastrin mRNA was quantitated by the competitive PCR method. The majority of cell lines expressed very low levels of gastrin mRNA (< 1-5 copies/cell); only one cell line expressed > 20 copies/cell. The mature carboxyamidated form of gastrin was not detected in any of the cell lines by radioimmunoassay or immunocytochemistry. Results suggested that either gastrin mRNA expressed by colon cancer cells was altered (mutated) or posttranslational processing of progastrin was incomplete. Gastrin cDNA from all the colon cancer cell lines had an identical sequence to the published sequence of human gastrin cDNA. Specific antibodies against precursor forms of gastrin were used, and significant concentrations of nonamidated (glycine-extended) and prepro forms of gastrin were measured in tumor extracts of representative colon cancer cell lines. The presence of precursor forms of gastrin suggested a lack of one or more of the processing enzymes and/or cofactors. Significant concentrations of the processing enzyme (peptidylglycine alpha-amidating monooxygenase) were detected in colon cancer cells by immunocytochemistry. Therefore, lack of other cofactors or enzymes may be contributing to incomplete processing of precursor forms of gastrin, which merits further investigation. Since low levels of gastrin mRNA were expressed by the majority of human colon cancer cell lines and progastrin was incompletely processed, it seems unlikely that gastrin can function as a viable autocrine growth factor for colon cancer cells. High concentrations of glycine-extended gastrin-17 (GG) (> 10(-6) M) were mitogenic for a gastrin-responsive human colon cancer (DLD-1) cell line in vitro. It remains to be seen if GG or other precursor forms of gastrin are similarly mitogenic in vivo, which may then lend credibility to a possible autocrine role of gastrinlike peptides in colon cancers.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14515-14515
Author(s):  
V. Dangles-Marie ◽  
P. Validire ◽  
S. Richon ◽  
L. Weiswald ◽  
M. Briffod ◽  
...  

14515 Background: In vitro spheroid model using cancer cell lines is widely admitted to mimic in vivo micro tumors, including micrometastases. Floating spheroid cell cluster culture has been recently used for normal and cancer stem cell expansion. Spontaneously spheroids generated in vivo have been only studied in ovarian cancer ascites while organoid aggregates have been sometimes observed in the establishment of human colon cancer cell lines. In this study, we investigated whether spontaneous spheroid aggregates from colon cancer could be isolated and characterized. Methods: 127 colorectal primary tumor specimens have been collected and mechanically dissociated into small fragments, which were then shortly cultured on cell plastic flask. Production of spheroid- like structures, referred to as colospheres, was examined at Day 1 and colospheres were gathered for phenotypic characterization. Results: Colospheres were successfully generated from 67 surgical specimens (53%). The capacity to form colospheres was strictly restricted to tumor tissue: dissociated normal colon mucosa never generated colospheres and colospheres were formed exclusively by cancer cells. The ability to generate colospheres was demonstrated to be significantly related to tumor aggressiveness, according to nodal status and AJCC’s stages (Chi-2 test, p<0.05). Immunohistochemical studies showed that cells forming colospheres were frequently positive for Ki67, and displayed often a disturbed expression of the epithelial caretaker E-cadherin. Peripheral cells of colospheres were able to migrate into Matrigel in absence of any chemoattractant. Conclusions: Collectively, the morphology of these colospheres derived directly from tumoral tissues and made up exclusively of cancer cells, their potential capacity to acquire an epithelial-to-mesenchymal transition phenotype and their in vitro migration ability could be aligned with the collective migration properties of carcinomas. Consequently, these ex vivo spherical structures might form an in vitro cell system for micrometastasis studies, at the very time when mortality among colorectal cancer patients continues to be attributed to metastasis development. No significant financial relationships to disclose.


2022 ◽  
Vol 11 ◽  
Author(s):  
Lihuiping Tao ◽  
Changliang Xu ◽  
Weixing Shen ◽  
Jiani Tan ◽  
Liu Li ◽  
...  

BackgroundExosomes are extracellular vesicles secreted by most cells to deliver functional cargoes to recipient cells. MicroRNAs (miRNAs) constitute a significant part of exosomal contents. The ease of diffusion of exosomes renders them speedy and highly efficient vehicles to deliver functional molecules. Cancer cells secrete more exosomes than normal cells. Reports have showed that exosomal miRNAs of cancer cells facilitate cancer progression. Yet the complexity of cancer dictates that many more functional exosomal miRNAs remain to be discovered.MethodsIn this study, we analyzed miRNA expression profiles of tissue and plasma exosome samples collected from 10 colorectal cancer (CRC) patients and 10 healthy individuals. We focused on hsa-miR-101-3p (101-3p), a profoundly up-regulated miRNA enriched in plasma exosomes of patients bearing CRC. We performed target analysis of 101-3p and pursued functional studies of this microRNA in two colorectal cancer cell lines, namely HCT116 and SW480.ResultsOur results indicated that inhibiting 101-3p slowed cell growth and retarded cell migration in vivo in two colorectal cancer cell lines. Target analysis showed that Homeodomain-interacting protein kinase (HIPK3) is a target of miR-101-3p. HCT116 and SW480 cells stably overexpressing HIPK3 showed increased level of phosphorylated FADD, as well as retarded cell growth, migration, and increased sensitivity to 5-FU. In-depth analysis revealed increased mitochondrial membrane potential upon HIPK3 overexpression along with increased production of reactive oxygen species, number of mitochondria, and expression of respiratory complexes. Measurements of glycolytic parameters and enzymes revealed decreased level of glycolysis upon HIPK3 overexpression in these two cell lines. Xenograft model further confirmed a profoundly improved potency of the synergistic treatment combining both 5-FU and 101-3p inhibitor compared to 5-FU alone.ConclusionThis study unraveled an oncogenic nature of the exosomal 101-3p and suggested a relationship between the 101-3p-HIPK3 axis and metabolic homeostasis in colorectal cancer. Expression level of 101-3p is positively correlated with glycolytic capacity in CRC and therefore 101-3p itself is an oncomiR. Combining 101-3p inhibitor with chemotherapeutic agents is an effective strategy against CRC.


2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Sooyeon Lim ◽  
Jin-Chul Ahn ◽  
Eun Jin Lee ◽  
Jongkee Kim

Abstract Sulforaphene (SFE), a major isothiocyanate in radish seeds, is a close chemical relative of sulforaphane (SFA) isolated from broccoli seeds and florets. The anti-proliferative mechanisms of SFA against cancer cells have been well investigated, but little is known about the potential anti-proliferative effects of SFE. In this study, we showed that SFE purified from radish seeds inhibited the growth of six cancer cell lines (A549, CHO, HeLa, Hepa1c1c7, HT-29, and LnCaP), with relative half maximal inhibitory concentration values ranging from 1.37 to 3.31 μg/mL. Among the six cancer cell lines, SFE showed the greatest growth inhibition against A549 lung cancer cells, where it induced apoptosis by changing the levels of poly(ADP-ribose) polymerase and caspase-3, -8, and -9. Our results indicate that SFE from radish seeds may have significant anti-proliferative potency against a broad range of human cancer cells via induction of apoptosis.


2019 ◽  
Vol 38 (4) ◽  
pp. 990-1002 ◽  
Author(s):  
Agnieszka Wróbel ◽  
Beata Kolesińska ◽  
Justyna Frączyk ◽  
Zbigniew J. Kamiński ◽  
Anna Tankiewicz-Kwedlo ◽  
...  

Summary This study provides new information on the cellular effects of 1,3,5-triazine nitrogen mustards with different peptide groups in DLD and Ht-29 human colon cancer cell lines. A novel series of 2,4,6-trisubstituted 1,3,5-triazine derivatives bearing 2-chloroethyl and oligopeptide moieties was designed and synthesized. The most cytotoxic derivative was triazine with an Ala-Ala-OMe substituent on the ring (compound 7b). This compound induced time- and dose-dependent cytotoxicity in the DLD-1 and HT-29 colon cancer cell lines. The triazine derivative furthermore induced apoptosis through intracellular signaling pathway attenuation. Compound 7b may be a candidate for further evaluation as a chemotherapeutic agent against colorectal cancer.


Materials ◽  
2019 ◽  
Vol 12 (6) ◽  
pp. 909 ◽  
Author(s):  
Marta Kutwin ◽  
Ewa Sawosz ◽  
Sławomir Jaworski ◽  
Mateusz Wierzbicki ◽  
Barbara Strojny ◽  
...  

Inefficient drug administration into cancer cells is related to the chemoresistance of cancer cells caused by genetic mutations including genes involved in drug transport, enzyme metabolism, and/or DNA damage repair. The objective of the present study was to evaluate the properties of platinum (NP-Pt), graphene oxide (GO), and the nanocomplex of GO functionalized with platinum nanoparticles (GO-NP-Pt) against several genetically, phenotypically, and metabolically different cancer cell lines: Colo205, HT-29, HTC-116, SW480, HepG2, MCF-7, LNCaP, and Hela B. The anticancer effects toward the cancer cell lines were evaluated by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxyanilide salt (XTT) and bromodeoxyuridine (BrdU) assays and measurements of cell apoptosis and morphology deformations. The NP-Pt and GO could effectively be introduced to cancer cells, but more effective delivery was observed after GO-NP-Pt treatment. The delivery of the GO-NP-Pt nanocomplex significantly decreased the viability of Colo 205 and HepG2 cells, but did not increase the cytotoxicity of other investigated cancer cells. The nanocomplex GO-NP-Pt also significantly increased the apoptosis of Colo 205 and HepG2 cancer cells. The obtained results suggest that the nanocomplex GO-NP-Pt is a remarkable nanostructure that can improve the delivery of Pt nanoparticles into cancer cells and has potential anticancer applications.


2020 ◽  
Vol 10 ◽  
Author(s):  
Abdi Wira Septama ◽  
Noor Azlina Abu Bakar ◽  
Nik Nurul Najihah Nik Mat Daud

Abstract:: Artocarpus heterophyllus, has been used as a folk medicine. This plant contained wide range of flavonoid compounds and possessed several pharmacological properties including anticancer. Chemotherapeutic agent is major option for cancer treatment. However, it may lead to tumor relapse. Therefore, it needs to discover alternative to reduce this limitation using natural products. Objective:: This study was aimed to determine anti-proliferative activities of isolated compounds against cancer cell lines. The morphological changes of cancer cell lines after treatment with the compounds was also evaluated. Methods:: The flavonoid compounds were determined for their cytotoxic activity against leukaemia HL-60 (CCL-240), colorectal adenocarcinoma HT-29 (HTB-38), breast adenocarcinoma cancer MCF-7 (HTB-22), and non-small lung cancer H460 (HTB-177) cell lines using MTT assay. Hoechst 33342/PI staining assay was used to evaluated the morphological changes, and observed using fluorescent microscope. Results:: It showed that amongst compound, artocarpin consistently exhibited strong cytotoxic activity against H460, HT-29, MCF-7, and HL-60 cancer cell lines with IC50 values of 5.07, 5.56, 12.53, and 19.94 μg/mL, respectively. The activity was comparable to the cisplatin as a positive control. Morphological observations showed the most typical apoptotic morphology of cancer cells upon treatment with artocarpin and the least typical of apoptotic structure with other compounds. Conclusion:: It can be suggested that A. heterophyllus bioactive compound modulates apoptosis by the presence of its distinctive, typical forms of morphological changes in treating cancer cells. Thus, artocarpin compound may provide high potential therapeutic use in chemotherapeutic strategies.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 592-592 ◽  
Author(s):  
Gaurav Goel ◽  
Krishnaveni Ramanan ◽  
Christof Kaltenmeier ◽  
Lin Zhang ◽  
Gordon J. Freeman ◽  
...  

592 Background: Colorectal cancer (CRC) is a major public health problem worldwide. Chemotherapy consisting of a fluoropyrimidine backbone constitutes a major therapeutic modality used in the treatment of CRC patients. However, cancer cells often develop resistance to such cytotoxic chemotherapy and this represents a major therapeutic challenge. B7-homolog 1 (B7-H1), also known as programmed death ligand-1 (PD-L1) is an immunoregulatory protein that belongs to the B7 family of T-cell co-regulatory molecules, and is overexpressed in several human tumors. Upregulation of PD-L1 expression is an important mechanism by which tumor cells can escape host T-cell immunity. Emerging evidence suggests that chemotherapeutic agents can regulate PD-L1 expression on cancer cells, which may have an impact on anti-tumor immunity and immune evasion. We performed this study to evaluate the effect of 5-Fluorouracil (5-FU) on PD-L1 expression in colon cancer cell lines, using an in vitro approach. Methods: Flow cytometry and western immunoblot analyses for PD-L1 expression were performed on human colon cancer cell lines (HCT116-WT, HCT116-p53 KO, SW480, HT29) upon treatment with IFN-ɣ and 5-FU. Results: We found that the tested human colon cancer cell lines rarely expressed PD-L1 protein on their cell surface at baseline, but a high level of expression was induced by treatment with IFN-ɣ. More importantly, we demonstrated that the chemotherapeutic agent 5-FU induces PD-L1 expression in colon cancer cells. Conclusions: It is therefore plausible that combining 5-FU with PD-1/PD-L1 blockade might help overcome some of the chemoresistance to 5-FU and thereby enhance its anti-cancer activity. Further experiments are being planned to formally test this hypothesis.


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