Human breast tumour cells viability effect of African Dioscorea Rotundata Tuber extracts in MCF-7 and MDA-MB231 cell lines

Abstract Background : Several Dioscorea species are used in Chinese medicine for tumours and Dioscorea species grown in Africa are yet to be tested to the best of knowledge for efficacy as cytotoxic agents. In Nigeria, the greatest producer of edible yams in the world, Dioscorea is the king of plants. Its tubers feeds millions of people and also function as ethnomedicine for diverse diseases. We aim to test the efficacy of edible Dioscorea species grown and consumed in Nigeria on two breast cancer cell lines; MCF-7 and MDA-MB231 derived from a luminal and a triple-negative breast cancer (TNBC) respectively and to confirm safety in non-tumour cells MCF-10A (normal breast cell lines) using a well established cytotoxic compound paclitaxel as a standard. Metastatic breast cancer is a prevalent cause of mortality in women around the world. Breast cancer therapies have greatly advanced in recent years, leading to the statement that cancer is not a death sentence but many patients develop cancer re-occurrence and metastasis and subsequently yield to the disease because of chemoresistance. Methods : Ethanolic extracts of Dioscorea rotundata boiled and raw (DiosB and DiosR) respectively were chemically analysed for the presence of diosgenin using HPLC and their cytotoxic activity was tested on MCF-7, MDA-MB-231 and MCF-10A cells I n vitro by MTT assay.Results : DiosB and DiosR extracts were more effective on MCF-7 than on MDA-MB231 cells showing a higher maximal effect on MCF-7 cells than on MDA-MB231 after 24 h and 48 h treatments (p<0.0001 and p<0.05 respectively). DiosR, if applied at a range between 50-70 g/ml, can be effective to reduce breast tumor cell viability without affecting non tumorigenic MCF-10A cells either at 24 h or at 48 h. African yams contain cytotoxic principles. DiosB showed an IC 50 of 38.83µg/ml while DiosR showed an IC 50 of 41.80µg/ml. Discussion : The results have shown that Dioscorea rotundata tubers could be used effectively to treat breast cancer tumors and this is in sync with its diosgenin content, a known cytotoxic compound and the use of other Dioscorea species for similar treatments in Asia etc. A major limitation will be in creating higher demand for the tuber which is consumed as a staple and at the moment affordable to all.Conclusion : There will be need to make consumers aware of the significant anticancer importance of D. rotundat a and a great need to increase its cultivation in order to make it sufficient as food and as medicine.

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HUMAN BREAST TUMOUR CELLS VIABILITY EFFECT OF AFRICAN DIOSCOREA ROTUNDATA TUBER EXTRACTS IN MCF-7 AND MDA-MB231 CELL LINES

10.1101/2020.05.08.084269 ◽

2020 ◽

Author(s):

Joy Ifunanya Odimegwu ◽

Olukemi Abiodun Odukoya ◽

Alejandro Español ◽

Maria Elena Sales

Keyword(s):

Breast Cancer ◽

Cell Lines ◽

Metastatic Breast ◽

Tumour Cells ◽

Breast Cancer Cell Lines ◽

Maximal Effect ◽

Dioscorea Rotundata ◽

Ethanolic Extracts ◽

Dioscorea Species ◽

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ABSTRACTObjectiveWe aim to test the efficacy of edible Dioscorea species grown and consumed in Nigeria, Africa on two breast cancer cell lines; MCF-7 and MDA-MB231 derived from a luminal and a triple-negative breast cancer (TNBC) respectively and to confirm safety in non-tumour cells MCF-10A using a well established cytotoxic compound paclitaxel as a standard. Metastatic breast cancer is a prevalent cause of mortality in women around the world. Breast cancer therapies have greatly advanced in recent years, but many patients develop cancer re-occurrence and metastasis and subsequently yield to the disease because of chemoresistance.MethodsEthanolic extracts of Dioscorea rotundata boiled and raw (DiosB and DiosR) respectively were chemically analysed for the presence of diosgenin using HPLC and the cytotoxic activity of the extracts were tested on MCF-7, MDA-MB-231 and MCF-10A cells In vitro by MTT assay.ResultsDiosB and DiosR extracts showed a higher maximal effect on MCF-7 cells than on MDA-MB231 after 24 h and 48 h treatments (p<0.0001 and p<0.05 respectively). DiosR, if applied at a range between 50-70 g/ml, can be effective to reduce breast tumor cell viability without affecting non tumorigenic MCF-10A cells either at 24 h or at 48 h. DiosB showed an IC50 of 38.83μg/ml while DiosR showed an IC50 of 41.80μg/ml.ConclusionThese results show that ethanolic extracts of Dioscorea rotundata tubers could be used effectively to treat breast cancer tumors and this is in sync with its diosgenin content as other Dioscorea species applied for similar treatments in Asia and elsewhere.

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Design, Synthesis and Cytotoxicity Evaluation of New 3, 5-Disubstituted-2-Thioxoimidazolidinones

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666171129213838 ◽

2018 ◽

Vol 18 (4) ◽

pp. 573-582 ◽

Cited By ~ 1

Author(s):

Khaled R.A. Abdellatif ◽

Mostafa M. Elbadawi ◽

Mohammed T. Elsaady ◽

Amer A. Abd El-Hafeez ◽

Takashi Fujimura ◽

...

Keyword(s):

Breast Cancer ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Topoisomerase I ◽

Cancer Cell Line ◽

Cytotoxic Agents ◽

Dependent Manner ◽

Human Lung Fibroblast ◽

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Background: Some 2-thioxoimidazolidinones have been reported as anti-prostate and anti-breast cancer agents through their inhibitory activity on topoisomerase I that is considered as a potential chemotherapeutic target. Objective: A new series of 3,5-disubstituted-2-thioxoimidazolidinone derivatives 10a-f and their S-methyl analogs 11a-f were designed, synthesized and evaluated for cytotoxicity against human prostate cancer cell line (PC-3), human breast cancer cell line (MCF-7) and non-cancerous human lung fibroblast cell line (WI-38). </P><P> Results and Method: While compounds 10a-f showed a broad range of activities against PC-3 and MCF-7 cell lines (IC50 = 34.0 – 186.9 and 24.6 – 147.5 µM respectively), the S-methyl analogs 11a-f showed (IC50 = 22.7 – 198.5 and 16.9 – 188.2 µM respectively) in comparison with 5-fluorouracil (IC50 = 60.7 and 40.7 µM respectively). 11c (IC50 = 22.7 and 29.2 µM) and 11f (IC50 = 28.7 and 16.9 µM) were the most potent among all compounds against both PC-3 and MCF-7 respectively with no cytotoxicity against WI-38. Conclusion: The newly synthesized compounds showed good activity against PC-3 and MCF-7 cell lines in comparison with 5-fluorouracil. Compounds 11c and 11f bound with human topoisomerase I similar to its known inhibitors and significantly inhibited its DNA relaxation activity in a dose dependent manner which may rationalize their molecular mechanism as cytotoxic agents.

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Cytotoxic activity and anti-cancer potential of Ontario grown onion extracts against breast cancer cell lines

Functional Foods in Health and Disease ◽

10.31989/ffhd.v8i3.408 ◽

2018 ◽

Vol 8 (3) ◽

pp. 159 ◽

Cited By ~ 1

Author(s):

Meghan Fragis ◽

Abdulmonem I. Murayyan ◽

Suresh Neethirajan

Keyword(s):

Breast Cancer ◽

Cytotoxic Activity ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Cancer Cell Lines ◽

Breast Cancer Cell Lines ◽

Cytotoxic Activities ◽

Cancer Line ◽

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Background: Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths among Canadian women. Cancer management through changes in lifestyle, such as increased intake of foods rich in dietary flavonoids, have been shown to decrease the risk associated with breast, liver, colorectal, and upper-digestive cancers in epidemiologic studies. Onions are high in flavonoid content and one of the most common vegetables. Additionally, onions are used in most Canadian cuisines.Methods: We investigated the effect of five prominent Ontario grown onion (Stanley, Ruby Ring, LaSalle, Fortress, and Safrane) extracts on two subtypes of breast cancer cell lines: a triple negative breast cancer line MDA-MB-231 and an ER+ breast cancer line MCF-7.Results: These onion extracts elicited strong anti-proliferative, anti-migratory, and cytotoxic activities on both the cancer cell lines. Flavonoids present in these onion extracts induced apoptosis, cell cycle arrest in the G2/M phase, and a reduction in mitochondrial membrane potential at dose-dependent concentrations. Onion extracts were more effective against MDA-MB-231 compared to the MCF-7 cell line. Conclusion: In this study, we investigated the extracts synthesized from Ontario-grown onion varieties in inducing anti-migratory, cytostatic, and cytotoxic activities in two sub-types of human breast cancer cell lines. Anti-tumor activity of these extracts depends upon the varietal and can be formulated into nutraceuticals and functional foods for the wellbeing of cancer patients. Overall, the results suggest that onion extracts are a good source of flavonoids with anti-cancerous properties.Keywords: onion extracts; flavonoids; anti-proliferative; breast cancer; cytotoxic activity

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Thieno[2,3-d]pyrimidin-4(3H)-one Derivatives of Benzimidazole as Potential Anti-Breast Cancer (MDA-MB-231, MCF-7) Agents.

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200721131431 ◽

2020 ◽

Vol 20 ◽

Author(s):

Stefan Dimov ◽

Anelia Ts. Mavrova ◽

Denitsa Yancheva ◽

Biliana Nikolova ◽

Iana Tsoneva

Keyword(s):

Breast Cancer ◽

Cell Lines ◽

Mechanism Of Action ◽

Biologically Active ◽

Breast Cancer Cell Lines ◽

3T3 Cells ◽

Fluorescence Study ◽

Compound 21 ◽

Mutational Activation ◽

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Aims: The purpose was the synthesis of some new thienopyrimidines derivative of 1,3-disubstituted benzimidazoles and the evaluation of their cytotoxicity towards MDA-MB-231 and MCF-7 cell lines as well 3T3 cells. Background: An overexpression or mutational activation of TK receptors EGFR and HER2/neu are characteristic for tumors. It has been found that some thieno[2,3-d]pyrimidines exhibit better inhibitory activity against epidermal growth factor receptor (EGFR/ErbB-2) tyrosine kinase in comparison to aminoquinazolines. Breast cancer activity towards MDAMB-231 and MCF-7 cell lines by inhibiting EGFR was revealed by a novel 2-arylbenzimidazole. This motivated the synthesis of new thienopyrimidines possessing benzimidazole fragment in order to evaluate their cytotoxicity to the above mentioned cell lines. Objective: The objectives were the design and synthesis of a novel series thieno[2,3-d]pyrimidines bearing biologically active moieties as 1,3-disubstituted-benzimidazole heterocycle structurally similar to diaryl ureas in order to evaluate their cytotoxicity against MDA-MB-231, MCF-7 breast cancer cell lines. Methods: N,N-disubstituted benzimidazole-2-one carbonitriles were synthesized by Aza-Michael addition and used as precursors to generate some of the new thieno[2,3-d]pyrimidines in acidic medium. The interaction of chloroethyl-2- thienopyrimidines and 2-amino-benzimidazole resp. benzimidazol-2-one nitriles under solid-liquid transfer catalysis conditions lead to obtaining of new thienopyrimidines. MTT assay for cells survival was performed in order to establish the cytotoxicity of the tested compounds. Fluorescence study was used to elucidate some aspect of mechanism. Results: The effect of nine of the synthesized compounds was investigated towards MDA-MB-231 and MCF-7 cells as well as to 3T3 cells. Thieno[2,3-d]pyirimidine-4-one 16 (IC50 – 0.058 μM) and 21 (IC50 – 0.029 μM) possess high cytotoxicity against MDA-MB-231 cells after 24h. The most toxic against breast cancer MCF-7 cells was compounds 21 (IC50 – 0.074 μM), revealing lower cytotoxicity towards mouse fibroblast 3T3 cells with IC50 – 0.20 μM. SAR analisys was performed. Fluorescence study of the treatment of MDA-MB cells with compound 21 was carried out in order to clarify some aspects of mechanism of action. Conclusion: The relationship between cytotoxicity of compounds 14 and 20 against MCF-7 and 3T3 cells can suggest a similar mechanism of action. The antitumor potential of the tested compounds proves the necessity for further investigation to estimate the exact inhibition pathway in the cellular processes. The fluorescence study of the treatment of MDA-MB cells with compound 21 showed a rapid process of apoptosis.

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Lemon Juice Mediated Synthesis of 3-Substituted Quinazolin-4(3H)-Ones and their Pharmacological Evaluation

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190723151909 ◽

2020 ◽

Vol 19 (16) ◽

pp. 2001-2009 ◽

Cited By ~ 1

Author(s):

Malavattu G. Prasad ◽

C. Vijaya Lakshmi ◽

Naresh K. Katari ◽

Sreekantha B. Jonnalagadda ◽

Manojit Pal

Keyword(s):

Cell Line ◽

Cell Lines ◽

Hek293 Cell ◽

Glyoxylic Acid ◽

Lemon Juice ◽

Cytotoxic Agents ◽

Diverse Range ◽

Hek293 Cell Line ◽

Three Component Reaction ◽

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Background: Compounds containing the quinazoline-4(3H)-one framework constitute an important class of fused N-heterocycles that are found in more than 200 naturally occurring alkaloids. These compounds also show a diverse range of pharmacological activities including antitumor properties. This prompted us to explore a series of quinazolin-4-(3H)-one derivatives having no substituent at C-2 as potential cytotoxic agents. Objective: The objective of this study was to synthesize and evaluate 3-substituted quinazolin-4(3H)-one derivatives for their potential cytotoxic properties. Methods: A convenient method has been developed for the rapid synthesis of this class of compounds under a mild and non-hazardous reaction condition in good yields. The methodology involved a three-component reaction employing isatoic anhydride, amines and glyoxylic acid as reactants in the presence of lemon juice in PEG- 400 at room temperature (25-30ºC) under ultrasound irradiation. All the synthesized compounds were screened via an MTT assay for their potential cytotoxic properties in vitro using the cancerous cell lines e.g. A549, A2780, HepG2, K562, MCF-7 and HCT-116 and a non-cancerous HEK293 cell line. Results: Several compounds such as 3a, 3b, 3d, 3e and 3f showed promising growth inhibition against these cancer cell lines but no significant effects on HEK293 cell line. The IC50 values of these compounds were comparable to doxorubicin whereas 3f significantly induced apoptosis in MCF-7 cells that also was comparable to doxorubicin. Conclusion: An ultrasound-assisted MCR facilitated by lemon juice has been developed to synthesize 3- substituted quinazolin-4(3H)-one derivatives that could act as potential anticancer agents.

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Design, Synthesis, In Vitro Anti-cancer Activity, ADMET Profile and Molecular Docking of Novel Triazolo[3,4-a]phthalazine Derivatives Targeting VEGFR-2 Enzyme

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180412123833 ◽

2018 ◽

Vol 18 (8) ◽

pp. 1184-1196 ◽

Cited By ~ 13

Author(s):

Abdel-Ghany A. El-Helby ◽

Helmy Sakr ◽

Rezk R.A. Ayyad ◽

Khaled El-Adl ◽

Mamdouh M. Ali ◽

...

Keyword(s):

Breast Cancer ◽

Molecular Docking ◽

Cell Lines ◽

Colon Adenocarcinoma ◽

Human Colon ◽

Kinase Assay ◽

Anticancer Activities ◽

In Silico Admet ◽

Human Colon Adenocarcinoma ◽

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Background: Extensive studies were reported in the synthesis of several phthalazine derivatives as promising anticancer agents as potent VEGFR-2 inhibitors. Vatalanib (PTK787) was the first anilinophthalazine published derivative as a potent inhibitor of VEGFR. The discovery of vatalanib as a clinical candidate led to the design and synthesis of different anilinophthalazine derivatives as potent inhibitors for VEGFR-2. The objective of present research work is the synthesis of new agents with the same essential pharmacophoric features of the reported and clinically used VEGFR-2 inhibitors (e.g vatalanib and sorafenib). The main core of our molecular design rationale comprised bioisosteric modification strategies of VEGFR-2 inhibitors at four different positions. </P><P> Material and Methods: A correlation between structure and biological activity of our designed phthalazines was established using molecular docking and VEGFR-2 kinase assay. Results and Discussion: In view of their expected anticancer activity, novel triazolo[3,4-a]phthalazine derivatives 5-6a-o and 3-substituted-bis([1,2,4]triazolo)[3,4-a:4',3'-c]phthalazines 9a-b were designed, synthesized and evaluated for their anti-proliferative activity against two human tumor cell lines HCT-116 human colon adenocarcinoma and MCF-7 breast cancer. It was found that, compound 6o the most potent derivative against both HCT116 and MCF-7 cancer cell lines. Compounds 6o, 6m, 6d and 9b showed the highest anticancer activities against HCT116 human colon adenocarcinoma with IC50 of 7±0.06, 13±0.11, 15±0.14 and 23±0.22 µM respectively while compounds 6o, 6d, 6a and 6n showed the highest anticancer activities against MCF-7 breast cancer with IC50 of 16.98±0.15, 18.2±0.17, 57.54±0.53 and 66.45±0.67 µM respectively. Sorafenib as a highly potent VEGFR-2 inhibitor was used as a reference drug with IC50 of 5.47±0.3 and 7.26±0.3 µM respectively. Nine compounds were further evaluated for their VEGFR-2 inhibitory activity. Compounds 6o, 6m, 6d and 9b emerged as the most active counterparts against VEGFR-2 with IC50 values of 0.1±0.01, 0.15±0.02, 0.28±0.03 and 0.38±0.04 µM, respectively comparable to that of sorafenib (IC50 = 0.1±0.02) µM. Furthermore, molecular docking studies were carried out for all synthesized compounds to investigate their binding pattern and predict their binding affinities towards VEGFR-2 active site. In silico ADMET studies were calculated for the tested compounds. Most of our designed compounds exhibited good ADMET profile. Conclusion: The obtained results showed that, the most active compounds could be useful as a template for future design, optimization, adaptation and investigation to produce more potent and selective VEGFR-2 inhibitors with higher anticancer analogs.

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