scholarly journals Cytotoxic Constituents of the Bark of Hypericum roeperianum towards Multidrug-Resistant Cancer Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Michel-Gael F. Guefack ◽  
Francois Damen ◽  
Armelle T. Mbaveng ◽  
Simplice Beaudelaire Tankeo ◽  
Gabin T. M. Bitchagno ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Colon Adenocarcinoma ◽  
Cancer Cell Lines ◽  
Multidrug Resistant ◽  
Leukemia Cells ◽  
Ros Production ◽  
Cytotoxic Effects ◽  
Induced Apoptosis

The global cancer burden remains a serious concern with the alarming incidence of one in eight men and one in eleven women dying in developing countries. This situation is aggravated by the multidrug resistance (MDR) of cancer cells that hampers chemotherapy. In this study, the cytotoxicity of the methanol extract (HRB), fractions (HRBa, HRBb, and HRBa1-5), and compounds from the bark of Hypericum roeperianum (HRB) was evaluated towards a panel of 9 cancer cell lines. The mode of action of the HRB and trichadonic acid (1) was also studied. Column chromatography was applied to isolate the constituents of HRB. The cytotoxicity of botanicals and phytochemicals was evaluated by the resazurin reduction assay (RRA). Caspase-Glo assay was used to evaluate the activity of caspases, and reactive oxygen species (ROS) (H2DCFH-DA) were assessed by flow cytometry. Phytochemicals isolated from HRB were trichadonic acid (1), fridelan-3-one (2), 2-hydroxy-5-methoxyxanthone (3), norathyriol (4), 1,3,5,6-tetrahydroxyxanthone (5), betulinic acid (6), 3′-hydroxymethyl-2′-(4″-hydroxy-3″,5″-dimethoxyphenyl)-5′,6′:5,6-(6,8-dihydroxyxanthone)-1′,4′-dioxane (7), and 3′-hydroxymethyl-2′-(4″-hydroxy-3″,5″-dimethoxyphenyl)-5′,6′:5,6-(xanthone)-1′,4′-dioxane (8). Botanicals HRB, HRBa, HRBa2-4, HRBb, and doxorubicin displayed cytotoxic effects towards the 9 tested cancer cell lines. The recorded IC50 values ranged from 11.43 µg/mL (against the P-glycoprotein (gp)-overexpressing CEM/ADR5000 leukemia cells) to 26.75 µg/mL (against HCT116 (p53+/+) colon adenocarcinoma cells) for the crude extract HRB. Compounds 1, 5, and doxorubicin displayed cytotoxic effects towards the 9 tested cancer cell lines with IC50 values varying from 14.44 µM (against CCRF-CEM leukemia cells) to 44.20 µM (against the resistant HCT116 (p53−/−) cells) for 1 and from 38.46 µM (against CEM/ADR5000 cells) to 112.27 µM (against the resistant HCT116 (p53−/−) cells) for 5. HRB and compound 1 induced apoptosis in CCRF-CEM cells. The apoptotic process was mediated by enhanced ROS production for HRB or via caspases activation and enhanced ROS production for compound 1. This study demonstrated that Hypericum roeperianum is a potential source of cytotoxic phytochemicals such as trichadonic acid and could be further exploited in cancer chemotherapy.

scholarly journals Cytotoxicity of Extracts from New Zealand Surf Clams Against Organ Cancer Cell Lines

Biomedicines ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 25 ◽  
Author(s):  
Tinu Odeleye ◽  
William White ◽  
Jun Lu
Keyword(s):  
New Zealand ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Cytotoxic Effects ◽  
Colon Cells ◽  
Surf Clam ◽  
Dependent Inhibition ◽  
Time Dependent Inhibition

In this study, we examined the cytotoxic effects of four fractions from three species of New Zealand (NZ) surf clam on four common organ cancer cells. In most cases, a dose- and time-dependent inhibition on the proliferation of the cancer cells was observed. This was most significant in WiDr (colon) cells, where the percentages of viability reduced to as low as 6%, 5%, and 17% (at 1000 µg 72 h) by extracts from Diamond shell, Storm shell, and Tua tua species, respectively. A549 (lung) cells were the least susceptible to the treatment, with viability percentages at 82%, 15%, and 45%, under the same conditions. Induction of caspase-dependent apoptosis and alterations to the cell cycle further supported the observed morphological analysis. The ethanol, petroleum ether, and ethyl acetate fractions of NZ surf clam, rich in lipids and proteins, were more potent than their water-based counterpart. This is the first demonstration where extracts from NZ surf clams show the ability to inhibit the growth and proliferation of cancer cell lines. We suggest that NZ surf clam extracts have the potential to be further studied and developed as candidates for cancer supplementary management/treatment.

Neferine-induced apoptosis is dependent on the suppression of Bcl-2 expression via downregulation of p65 in renal cancer cells

2019 ◽  
Vol 51 (7) ◽  
pp. 734-742 ◽  
Author(s):  
Eun-Ae Kim ◽  
Eon-Gi Sung ◽  
In-Hwan Song ◽  
Joo-Young Kim ◽  
Hwa-Jung Sung ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Western Blot ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Renal Cancer ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Cancer Cell Lines ◽  
Induced Apoptosis

Abstract Neferine is an alkaloid extracted from a seed embryo of Nelumbo nucifera and has recently been shown to have anticancer effects in various human cancer cell lines. However, the detailed molecular mechanism of neferine-induced apoptosis has not been elucidated in renal cancer cells. In the present study, we observed that neferine induced inhibition of cell proliferation and apoptosis in Caki-1 cells in a dose-dependent manner by using MT assay and flow cytometry and that neferine-mediated apoptosis was attenuated by pretreatment with N-benzyloxycarbony-Val-Ala-Asp (O-methyl)-fluoromethyketone, a pan-caspase inhibitor. Treatments with neferine dose-dependently downregulated B cell lymphoma-2 (Bcl-2) expression at the transcriptional level determined by reverse transcriptase-polymerase chain reaction. The forced expression of Bcl-2 and p65 attenuated the neferine-mediated apoptosis in Caki-1 cells. In addition, neferine induced apoptosis by downregulating Bcl-2 and p65 expression in the other two kidney cancer cell lines determined by flow cytometry and western blot analysis. Finally, we observed that treatment with neferine induced apoptosis by inhibiting the NF-κB pathway through caspase-mediated cleavage of the p65 protein by western blot analysis. Collectively, this study demonstrated that neferine-induced apoptosis is mediated by the downregulation of Bcl-2 expression via repression of the NF-κB pathway in renal cancer cells.

Apigenin Inhibits Growth of Breast Cancer Cells: The Role of ERα and HER2/neu

Acta Naturae ◽  
2015 ◽  
Vol 7 (3) ◽  
pp. 133-139 ◽  
Author(s):  
A. M. Scherbakov ◽  
O. E. Andreeva
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Lines ◽  
Luciferase Reporter ◽  
Her2 Positive ◽  
Cytotoxic Effects ◽  
High Doses

Phytoestrogens are a group of plant-derived compounds with an estrogen-like activity. In mammalians, phytoestrogens bind to the estrogen receptor (ER) and participate in the regulation of cell growth and gene transcription. There are several reports of the cytotoxic effects of phytoestrogens in different cancer cell lines. The aim of this study was to measure the phytoestrogen activity against breast cancer cells with different levels of ER expression and to elucidate the molecular pathways regulated by the leader compound. Methods used in the study include immunoblotting, transfection with a luciferase reporter vector, and a MTT test. We demonstrated the absence of a significant difference between ER+ and ER- breast cancer cell lines in their response to cytotoxic stimuli: treatment with high doses of phytoestrogens (apigenin, genistein, quercetin, naringenin) had the same efficiency in ER-positive and ER-negative cells. Incubation of breast cancer cells with apigenin revealed the highest cytotoxicity of this compound; on the contrary, naringenin treatment resulted in a low cytotoxic activity. It was shown that high doses of apigenin (50 М) do not display estrogen-like activity and can suppress ER activation by 17-estradiol. Cultivation of HER2-positive breast cancer SKBR3 cells in the presence of apigenin resulted in a decrease in HER2/neu expression, accompanied by cleavage of an apoptosis substrate PARP. Therefore, the cytotoxic effects of phytoestrogens are not associated with the steroid receptors of breast cancer cells. Apigenin was found to be the most effective phytoestrogen that strongly inhibits the growth of breast cancer cells, including HER2-positive ones.

Advances of proteomics technologies for multidrug-resistant mechanisms

2019 ◽  
Vol 11 (19) ◽  
pp. 2573-2593 ◽  
Author(s):  
Tiantian Zhang ◽  
Qijuan Yuan ◽  
Zhipeng Gu ◽  
Changhu Xue
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Large Scale ◽  
Cancer Cell Lines ◽  
Multidrug Resistant ◽  
Drug Induced ◽  
Dna Repair Mechanisms ◽  
Repair Mechanisms ◽  
Recent Developments ◽  
Induced Apoptosis

Multidrug resistance (MDR) is a vital issue in cancer treatment. Drug resistance can be developed through a variety of mechanisms, including increased drug efflux, activation of detoxifying systems and DNA repair mechanisms, and escape of drug-induced apoptosis. Identifying the exact mechanism related in a particular case is a difficult task. Proteomics is the large-scale study of proteins, particularly their expression, structures and functions. In recent years, comparative proteomic methods have been performed to analyze MDR mechanisms in drug-selected model cancer cell lines. In this paper, we review the recent developments and progresses by comparative proteomic approaches to identify potential MDR mechanisms in drug-selected model cancer cell lines, which may help understand and design chemical sensitizers.

scholarly journals Antiproliferation effect of sulforaphene isolated from radish (Raphanus sativus L.) seeds on A549 cells

2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Sooyeon Lim ◽  
Jin-Chul Ahn ◽  
Eun Jin Lee ◽  
Jongkee Kim
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
A549 Cells ◽  
Cancer Cell Lines ◽  
Human Cancer Cells ◽  
Induced Apoptosis ◽  
Ht 29 ◽  
A549 Lung

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.

Bovine lactoferrin and lactoferrin peptides affect endometrial and cervical cancer cell lines

2020 ◽  
Author(s):  
Diana A. Ramírez-Sánchez ◽  
Izamar G. Arredondo-Beltran ◽  
Adrian Canizalez-Roman ◽  
Hector Flores-Villaseñor ◽  
Kamran Nazmi ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Morphological Changes ◽  
Uterine Cancer ◽  
Female Genital Tract ◽  
Cancer Cell Lines ◽  
Bovine Lactoferrin ◽  
Additive Interaction ◽  
Induced Apoptosis

Cervical, uterine and ovarian cancers are the most common malignancies of the female genital tract worldwide. In spite of advances in prevention, early diagnosis, effective screening, and treatment programs, mortality remains high. Consequently, it is important to search for new treatments. The activity of bovine Lactoferrin (bLF) and LF-peptides against several types of cancer has been studied, however, there are only a few studies reporting the effect of bLF and LF-peptides against cervical and endometrial cancers. In this study, we explored the effect of bLF, LFchimera and its constituent peptides LFcin17-30 and LFampin265-284 on the viability of cervical (HeLa, SiHa) and endometrial (KLE, HEC-1A) cancer cell lines. Cell proliferation was quantified with an MTT assay; cell morphological changes and damage were determined by Giemsa and phalloidin-TRITC and DAPI staining; and apoptotic and necrotic cells were identified by Alexa Fluor® 488 Annexin V and PI staining. Additionally, the effect of combinations of bLF and LF-peptides with cisplatin was assessed. BLF and LF-peptides inhibited the proliferation of uterine cancer cells and caused cellular morphological changes and damage to cell monolayers. BLF induced apoptosis; LFcin17-30 and LFampin265-284 induced apoptosis and necrosis, and LFchimera induced necrosis. Additionally, bLF and LFchimera showed an additive interaction with cisplatin against uterine cancer cells.

scholarly journals Demethylation of TMS1 Gene Sensitizes Thyroid Cancer Cells to TRAIL-Induced Apoptosis

2010 ◽  
Vol 24 (11) ◽  
pp. 2241-2242
Author(s):  
Abdul K. Siraj ◽  
Azhar R. Hussain ◽  
Maha Al-Rasheed ◽  
Maqbool Ahmed ◽  
Prashant Bavi ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Methylation Status ◽  
Cancer Cell Lines ◽  
Thyroid Cancer Cell ◽  
Induced Apoptosis ◽  
Thyroid Cancer Cell Lines ◽  
Thyroid Cancer Cells

Abstract Context: TMS1 is a tumor suppressor gene that encodes for caspase recruitment domain containing regulatory protein and has been shown to be hypermethylated in various cancers. However, its methylation status has not been investigated in thyroid cancer. Therefore, we studied the methylation of TMS1 and its functional consequence in thyroid cancer. Design: The methylation status of the promoter region of the TMS1 gene was determined using methylation-specific PCR in 40 papillary thyroid cancer samples, 10 normal thyroid tissue, and seven thyroid cancer cell lines. RT-PCR and Western blot analysis were used to assess the expression levels. 5-aza-2′-deoxycytidine was used to demethylate the thyroid cancer cell lines. Cell viability and apoptosis was determined by dimethylthiazoldiphenyltetra-zoliumbromide and flow cytometry. Results: Twenty-three percent of the papillary thyroid carcinoma samples were found to be methylated for the TMS1 gene. Two of seven thyroid cell lines were either completely or partially methylated for the TMS1 gene. The treatment of methylated thyroid cancer cell lines with 5-aza-2′-deoxycytidine resulted in the demethylation of the TMS1 gene leading to the restoration of its expression. After demethylation, treatment of cells with TNF-related apoptosis-inducing ligand (TRAIL) led to the induction of apoptosis via activation of caspases-8, caspase-3, and poly(ADP-ribose) polymerase. Interestingly, gene silencing of TMS1 using TMS1-specific small interfering RNA prevented TRAIL-mediated apoptosis. Conclusion: Our results demonstrated that the TMSI gene is methylated in thyroid cancer cells and repression of methylation by 5-aza-2′-deoxycytidine restored expression of the TMS1 gene and sensitized cells to TRAIL-induced apoptosis. These findings suggest that the TMS1 gene can be targeted by combination of demethylating agents with TRAIL to induce efficient apoptosis in thyroid cancer cells.

scholarly journals Sulforaphene Isolated from Radish (Raphanus Sativus L.) Seeds Inhibits Growth of Six Cancer Cell Lines and Induces Apoptosis of A549 Cells

2018 ◽  
Author(s):  
Sooyeon Lim ◽  
Jinchul Ahn ◽  
Eun Jin Lee ◽  
jongkee Kim
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
A549 Cells ◽  
Adenosine Diphosphate ◽  
Cancer Cell Lines ◽  
Human Cancer Cells ◽  
Ic50 Values ◽  
Induced Apoptosis

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 (IC50) values ranging from 1.37 to 3.31 g/mL. Among the six cancer cell lines evaluated, SFE showed the greatest growth inhibition against A549 lung cancer cells. In A549 cells, SFE induced apoptosis via changes in the levels of poly (adenosine diphosphate 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.

scholarly journals Autophagy inhibition enhances Matrine derivative MASM induced apoptosis in cancer cells via a mechanism involving reactive oxygen species-mediated PI3K/Akt/mTOR and Erk/p38 signaling

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuming Zou ◽  
Melika Sarem ◽  
Shengnan Xiang ◽  
Honggang Hu ◽  
Weidong Xu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Reactive Oxygen ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Oxygen Species ◽  
Induced Apoptosis

Abstract Background In the quest for new anti-cancer drugs, the drug discovery process has shifted to screening of active ingredients in traditional eastern medicine. Matrine is an active alkaloid isolated from plants of the Sophora genus used in traditional Chinese herbal medicine that exhibits a wide spectrum of biological properties and has a potential as an anti-proliferative agent. In this study, we investigated the anticancer property of MASM, ([(6aS, 10S, 11aR, 11bR, 11cS)210-Methylamino-dodecahydro-3a, 7a-diaza-benzo (de)anthracene-8-thione]), a potent derivative of matrine. Methods Four epithelial cancer cell lines representing the dominant cancers, namely: A549 (non-small-cell lung cancer cell line), MCF-7 and MDA-MB-231 (breast cancer cell lines), and Hela (cervical cancer cell line) were employed, and the mechanistic underpinning of MASM-induced apoptosis was investigated using flow cytometry, western blot and immunofluorescence. Results MASM, induced apoptosis via caspase 3 dependent and independent pathways, and autophagy in all the four cancer cell lines, but post-EMT (epithelial mesenchymal transition) cells showed greater sensitivity to MASM. Scavenging reactive oxygen species using N-acetylcysteine rescued all cancer cell lines from apoptosis and autophagy. Mechanistic analysis revealed that MASM induced autophagy involves inhibition of Akt signaling and the activation of Erk and p38 signaling, and inhibition of autophagy further enhanced the apoptosis induced by MASM. Conclusions These results indicate that MASM possesses potency against cancer cells and modulating autophagy during MASM administration could be used to further enhance its therapeutic effects.

scholarly journals Cytotoxicity and Modes of Action of the Methanol Extracts of Six Cameroonian Medicinal Plants against Multidrug-Resistant Tumor Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Victor Kuete ◽  
Aimé G. Fankam ◽  
Benjamin Wiench ◽  
Thomas Efferth
Keyword(s):  
Cell Cycle ◽  
Medicinal Plants ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Multidrug Resistant ◽  
Cycle Arrest ◽  
Enhanced Production ◽  
Resazurin Assay ◽  
Induced Apoptosis

Introduction. The present study aims at evaluating the cytotoxicity of twelve parts from six Cameroonian medicinal plants on sensitive and drug-resistant cancer cell lines. We also studied the mode of action of the most active plants,Gladiolus quartinianus,Vepris soyauxii, andAnonidium mannii.Methods. The cytotoxicity of the extracts was determined using a resazurin assay. Flow cytometry was used for cell-cycle analysis and detection of apoptosis, analysis of mitochondrial membrane potential (MMP), and measurement of reactive oxygen species (ROS).Results. At 40 g/mL, three extracts showed a growth of CCRF-CEM leukemia cells by less than 50%. This includes the extracts fromG. quartinianus(GQW; 25.69%),Vepris soyauxiileaves (VSL; 29.82%), andAnonidium manniileaves (AML; 31.58%). The lowest IC50values below 30 μg/mL were obtained with GQW, AML and VSL against 7/9, 8/9, and 9/9 tested cancer cell lines, respectively. The lowest IC50values for each plant were 4.09 μg/mL, and 9.14 μg/mL (against U87MG.ΔEGFRcells), respectively, for VSL and AML and 10.57 μg/mL (against CCRF-CEM cells) for GQW. GQW induced cell cycle arrest between G0/G1 and S phases, whilst VSL and AML induced arrest in G0/G1. All three extracts induced apoptosis in CCRF-CEM cells by loss of MMP, whilst AML also enhanced production of ROS.Conclusion. The three active plants may be a source for the development of new anticancer drugs.

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