Inhibition Capacity of the n-Hexane Fraction of Myrmecodia pendens as a Potential Anti-Cancer in Breast and Cervical Cancer: In Vitro Study

Breast cancer (BC) and cervical cancer (CC) have a high prevalence and mortality rate worldwide. Despite the availability of advanced treatment, resistance to conventional chemotherapies has emerged. Myrmecodia pendens, one of the species of Sarang Semut (local name), possess a potential of antitumor effects by inducing cell death different cancer cell entities. This study aimed to assess anti-tumor activities of n-hexane fraction of M. pendens in inhibiting cell survival and cell migration in BC and CC cells. M. pendens was extracted in methanol then fractionated using n-hexane or ethyl acetate. BC cells including MCF-7 (luminal A), HCC-1954 (HER2+) cells and CC Hela cells were treated with M. pendens extracts to evaluate cytotoxic activity using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay as well as anti-cell migration using scratch assay. We also analyzed inhibitory concentration 50 (IC50) of n-hexane fraction in BC and CC cells. We started with comparing cytotoxicity activities of methanol extract, ethyl acetate and n-hexane fractions of M. pendens. Data showed that the n-hexane fraction was the most potent inducing BC cell death. Therefore, we used the n-hexane fraction for further experiments. Interestingly, IC50 of this fraction in HCC-1954 and Hela cells were lower than in MCF-7 cells, 16; 13 and 60 ppm, respectively. Moreover, the low concentrations of n-hexane fraction inhibited HeLa cells migration, compared to control group (p<0.05). The n-hexane fraction of M. pendens shows promising anti-cancer agent, by inhibiting BC and CC cell survival as well as inhibiting CC cells migration.Keywords: breast cancer, cervical cancer, MTT assay, Sarang Semut, scratch assay

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Differential Mechanisms of Cell Death Induced by HDAC Inhibitor SAHA and MDM2 Inhibitor RG7388 in MCF-7 Cells

Cells ◽

10.3390/cells8010008 ◽

2018 ◽

Vol 8 (1) ◽

pp. 8 ◽

Cited By ~ 5

Author(s):

Umamaheswari Natarajan ◽

Thiagarajan Venkatesan ◽

Vijayaraghavan Radhakrishnan ◽

Shila Samuel ◽

Appu Rathinavelu

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Death ◽

Cancer Cells ◽

Hdac Inhibitor ◽

The Other ◽

Combination Treatments ◽

Cycle Arrest ◽

Anti Cancer ◽

Mcf 7

Gene expression is often altered by epigenetic modifications that can significantly influence the growth ability and progression of cancers. SAHA (Suberoylanilide hydroxamic acid, also known as Vorinostat), a well-known Histone deacetylase (HDAC) inhibitor, can stop cancer growth and metastatic processes through epigenetic alterations. On the other hand, Letrozole is an aromatase inhibitor that can elicit strong anti-cancer effects on breast cancer through direct and indirect mechanisms. A newly developed inhibitor, RG7388 specific for an oncogene-derived protein called MDM2, is in clinical trials for the treatment of various cancers. In this paper, we performed assays to measure the effects of cell cycle arrest resulting from individual drug treatments or combination treatments with SAHA + letrozole and SAHA + RG7388, using the MCF-7 breast cancer cells. When SAHA was used individually, or in combination treatments with RG7388, a significant increase in the cytotoxic effect was obtained. Induction of cell cycle arrest by SAHA in cancer cells was evidenced by elevated p21 protein levels. In addition, SAHA treatment in MCF-7 cells showed significant up-regulation in phospho-RIP3 and MLKL levels. Our results confirmed that cell death caused by SAHA treatment was primarily through the induction of necroptosis. On the other hand, the RG7388 treatment was able to induce apoptosis by elevating BAX levels. It appears that, during combination treatments, with SAHA and RG7388, two parallel pathways might be induced simultaneously, that could lead to increased cancer cell death. SAHA appears to induce cell necroptosis in a p21-dependent manner, and RG7388 seems to induce apoptosis in a p21-independent manner, outlining differential mechanisms of cell death induction. However, further studies are needed to fully understand the intracellular mechanisms that are triggered by these two anti-cancer agents.

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The Effects of Apigenin and Curcumin on Autophagy Related Cell Death and Apoptosis

Proceedings ◽

10.3390/proceedings2251586 ◽

2018 ◽

Vol 2 (25) ◽

pp. 1586

Author(s):

Sera Kayacan ◽

Kaan Yilancioglu ◽

Ayse Seda Akdemir ◽

Fatma Kaya Dagistanli ◽

Gulay Melikoglu ◽

...

Keyword(s):

Cervical Cancer ◽

Cell Death ◽

Natural Products ◽

Plant Extracts ◽

Mtt Assay ◽

Hela Cells ◽

Qrt Pcr ◽

Antiviral Effects ◽

Related Cell ◽

Promising Therapeutic Approach

: Cervical cancer is one of the frequent types of cancer seen in females. It has been suggested that natural compounds can be used effectively for cancer treatment. Apoptosis and autophagy related cell death play important roles in suppression of tumorigenesis. Apigenin and curcumin are natural products isolated from plant extracts known to have antitumoral, antibacterial and antiviral effects. Varying doses of curcumin and apigenin were applied to HeLa cancer cell lines. The expression of the genes related to apoptosis and/or autophagy related cell death were measured using qRT-PCR and cell viability was measured using MTT assay. Our results showed that curcumin and apigenin are effective on apoptosis and autophagy related cell death in HeLa cells. We suggested that these natural products seem to be a new promising therapeutic approach in cancer.

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Anti-cancer effect of Urginea maritima bulb extract invitro through cell cycle arrest and induction of apoptosis in human breast cancer cell lines

Current Drug Discovery Technologies ◽

10.2174/1570163817666200817111703 ◽

2020 ◽

Vol 17 ◽

Author(s):

Khadije Saket ◽

Roshanak Salari ◽

Ehsan Saburi ◽

Mahdi Yousefi ◽

Mohammad Ali Khodadoust ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Migration ◽

Cell Cycle Arrest ◽

Breast Cancer Cell ◽

Breast Cancer Cell Lines ◽

Cycle Arrest ◽

Anti Cancer ◽

Induction Of Apoptosis ◽

Mcf 7

Background: Breast cancer is the most common known malignancy in women and it is therefore very important to prevent and treat this cancer. In this experimental study, the anti-breast cancer effect of Urginea matrima was investigated. Method: Breast cancer cell lines [MCF-7 and MDA-MB231] and L929 normal cells [as a control group] were cultivated in DMEM medium. Bulb aqueous and hydroalcoholic extracts [70:30] were prepared through maceration method. The cultured cells were treated with different concentrations [6, 3, 1.5, 0.75, 0.375, 0.187 and 0.093 μg/mL] of U.maritima extracts for 24, 48 and 72 h. Toxicity of the extracts on cells were examined using MTT test. The Annexin V–FITC Apoptosis Detection Kit was used to evaluate apoptosis and necrosis. Flow cytometry technique was employed to evaluate the cell cycle and the cell migration was evaluated by Scratch method. Data were analyzed by GraphPad Prism and SPSS software and P <0.05 was considered significant. Result: Results showed that both extracts of U.maritima in the concentration of 1.5 and 3 μg/ ml at 24,48 and 72h presented cytotoxicity effect on MCF7 cell line . Also, both extracts in the concentration of 3 μg/ ml at 24 and 72h, and in the concentration of 6 μg/ ml at 72h showed cytotoxicity effect significantly on MDA-MB231 cells. In addition, the plant extracts at the dosage of 3 and 6 μg/ ml induced an accumulation of G0/G1 cells, as well as reduce in S and G2/M phases in MCF-7 and MDA-MB231 cells. Moreover, the aqueous and hydroalcoholic of U.maritima extracts at three concentrations [ 1.5, 3 and 6 μg/ ml ] in 24h inhibited the cell migration by 60% up to 70% respectively. In addition, the content of phenolic compounds in both extracts [aqueous and hydroalcoholic] was 7 mg and 10 mg gallic acid equivalent per gram of the crude extract, respectively. Conclusion: Our results suggest that U.maritima extracts has significant anti-cancer activity against breast cancer cells due to cell cycle arrest and induction of apoptosis pathway.

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Anti-cancer Effects of Epigenetics Drugs Scriptaid and Zebularine in Human Breast Adenocarcinoma Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666210608103251 ◽

2021 ◽

Vol 21 ◽

Author(s):

Zhi Hung Yap ◽

Wei Yang Kong ◽

Abdur Rahmaan Azeez ◽

Chee-Mun Fang ◽

Siew Ching Ngai

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Migration ◽

Histochemical Staining ◽

Breast Adenocarcinoma ◽

Nuclear Chromatin ◽

Human Breast ◽

Human Breast Adenocarcinoma ◽

Anti Cancer ◽

Mcf 7

Background: High relapse and metastasis progression in breast cancer patients have prompted the need to explore alternative treatments. Epigenetic therapy has emerged as an attractive therapeutic strategy due to the reversibility of epigenome structures. Objective: This study investigated the anti-cancer effects of epigenetic drugs scriptaid and zebularine in human breast adenocarcinoma MDA-MB-231 and MCF-7 cells. Methods: First, the half maximal inhibitory concentration (IC50) of scriptaid, zebularine and the combination of both drugs on human breast adenocarcinoma MDA-MB-231 cells was determined. Next, MDA-MB-231 and MCF-7 cells were treated with scriptaid, zebularine and the combination of both. After treatments, the anti-cancer effects were evaluated via cell migration assay, cell cycle analysis and apoptotic studies, which included histochemical staining and reverse-transcriptase polymerase chain reaction (RT-PCR) of the apoptotic genes. Results: Both epigenetic drugs inhibited cell viability in a dose-dependent manner with 2 nM scriptaid, 8 µM zebularine and combination of 2 nM scriptaid and 2 µM zebularine. Both MDA-MB-231 and MCF-7 cells exhibited a reduction in cell migration after the treatments. In particular, MDA-MB-231 cells exhibited a significant reduction in cell migration (p < 0.05) after the treatments of zebularine and the combination of scriptaid and zebularine. Besides, cell cycle analysis demonstrated that scriptaid and the combination of both drugs could induce cell cycle arrest at the G0/G1 phase in both MDA-MB-231 and MCF-7 cells. Furthermore, histochemical staining allowed the observation of apoptotic features, such as nuclear chromatin condensation, cell shrinkage, membrane blebbing, nuclear chromatin fragmentation and cytoplasmic extension, in both MDA-MB-231 and MCF-7 cells after the treatments. Further apoptotic studies revealed that the upregulation of pro-apoptotic Bax, downregulation of anti-apoptotic Bcl-2 and elevation of Bax/Bcl-2 ratio were found in MDA-MB-231 cells treated with zebularine and MCF-7 cells treated with all drug regimens. Conclusion: Collectively, these findings suggest that scriptaid and zebularine are potential anti-cancer drugs, either single or in combination, for the therapy of breast cancer. Further investigations of the gene regulatory pathways directed by scriptaid and zebularine are definitely warranted in the future.

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Ricinus communis Butanol Fraction Inhibits MCF-7 Breast Cancer Cell Migration, Adhesion, and Invasiveness

Integrative Cancer Therapies ◽

10.1177/1534735420977684 ◽

2021 ◽

Vol 20 ◽

pp. 153473542097768

Author(s):

Rixile Mabasa ◽

Kholofelo Malemela ◽

Karabo Serala ◽

Mante Kgakishe ◽

Thabe Matsebatlela ◽

...

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Cell Migration ◽

Cell Viability ◽

Apoptotic Cell ◽

Ricinus Communis ◽

Gelatin Zymography ◽

Apoptotic Cell Death ◽

Butanol Fraction ◽

Mcf 7

In this study, the potential of an n-butanol fraction from Ricinus communis to prevent metastasis in MCF-7 breast cancer cells was investigated. The effect of the fraction on BUD-8 and MCF-7 cell viability was assessed using the MTT assay. Apoptotic cell death was analyzed by Hoechst staining assay. The antimetastatic effect of the fraction on MCF-7 cell was evaluated using the wound healing, adhesion and Boyden chamber invasion assays. Gelatin-zymography was used to assess the effect of the fraction on MMP-2 and MMP-9 activity. The expression profile of proteins implicated in metastasis and angiogenesis was determined using the human angiogenesis antibody array kit, following treatment with the fraction. BUD-8 cell viability was significantly reduced at concentrations between 300 and 500 µg/ml of the extract. In contrast, a significant reduction in cell viability was seen in MCF-7 cells treated with 400 to 500 µg/ml of the fraction. At sub-lethal concentrations (100 and 200 µg/ml) of the fraction, no nuclei morphological changes associated with apoptotic cell death were observed in MCF-7 cells. In addition, the fraction showed to have an inhibitory effect on MCF-7 cell migration, adhesion, invasiveness, and MMP-2 activity. Moreover, the fraction was seen to modulate the expression of several proteins, such as MMP-9, uPA, VEGF, and TGF-β1, playing a role in the metastasis process. This study demonstrates that the n-butanol fraction of R. communis can inhibit major steps of the metastatic cascade and modulate metastasis regulatory proteins. Thus, the fraction can be considered a potential source of antimetastatic agents that could be useful in the treatment of malignant cancers.

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Extracts of edible, medicinal Thai plants inhibit the human breast cancer cells

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i3.20 ◽

2020 ◽

Vol 19 (3) ◽

pp. 595-601

Author(s):

Benjaporn Buranrat ◽

Ampa Konsue ◽

Pornpimon Wongsuwan

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cell Death ◽

Cell Migration ◽

Cancer Cell ◽

Plant Extracts ◽

Azadirachta Indica ◽

Piper Nigrum ◽

Cancer Cell Death ◽

Mcf 7

Purpose: To evaluate the effects of ten edible, medicinal Thai plant extracts on MCF-7 cell viability and cell migration, as well as their mechanism(s) of action. Methods: Ethanolic plant extracts of ten edible, medicinal plants were tested for their cytotoxicity against MCF-7 cells using sulforhodamine B (SRB). To investigate the cytotoxic mechanism(s) of action of these extracts, the study was examined gene expression and protein expression by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Cell migration was studied by wound healing assay. Results: Four of the ten test extracts were potently cytotoxic, Careya sphaerica (CS), Azadirachta indica (AI), Piper nigrum (PN) and Oroxylum indicum (OI) with half maximal inhibitory concentrations (IC50) less than 100 μg/mL. All four extracts stimulated ROS overgeneration, increased caspase 3 activity and decreased growth-related gene expression including cdk2, cdk4, cdk6, cyclin D1 and cyclin E. Furthermore, the extracts significantly enhanced cyclin-dependent kinase inhibitor (CDKI) p21 levels and activated cancer cell death. The four extracts, CS, AI, PN and OI, also significantly reduced cancer cell migration, with PN being the most potent. Conclusion: Extract of the edible plants CS, AI, PN and OI have in vitro anticancer activity and are promising starting points for the development of breast cancer drugs. Keywords: Careya sphaerica (CS), Azadirachta indica (AI), Piper nigrum (PN), Oroxylum indicum (OI), Breast cancer, Cell death

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The Antitumor Efficiency of Zinc Finger Nuclease Combined with Cisplatin and Trichostatin A in Cervical Cancer Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200804102300 ◽

2020 ◽

Vol 20 (17) ◽

pp. 2125-2135

Author(s):

Ci Ren ◽

Chun Gao ◽

Xiaomin Li ◽

Jinfeng Xiong ◽

Hui Shen ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Zinc Finger ◽

Hela Cells ◽

Colony Formation ◽

Trichostatin A ◽

Combined Therapy ◽

Hpv E7 ◽

Anti Cancer ◽

Cervical Cancer Cells

Background: Persistent infection with the high-risk of human papillomavirus (HR-HPVs) is the primary etiological factor of cervical cancer; HR-HPVs express oncoproteins E6 and E7, both of which play key roles in the progression of cervical carcinogenesis. Zinc Finger Nucleases (ZFNs) targeting HPV E7 induce specific shear of the E7 gene, weakening the malignant biological effects, hence showing great potential for clinical transformation. Objective: Our aim was to develop a new comprehensive therapy for better clinical application of ZFNs. We here explored the anti-cancer efficiency of HPV targeted ZFNs combined with a platinum-based antineoplastic drug Cisplatin (DDP) and an HDAC inhibitor Trichostatin A (TSA). Methods: SiHa and HeLa cells were exposed to different concentrations of DDP and TSA; the appropriate concentrations for the following experiments were screened according to cell apoptosis. Then cells were grouped for combined or separate treatments; apoptosis, cell viability and proliferation ability were measured by flow cytometry detection, CCK-8 assays and colony formation assays. The xenograft experiments were also performed to determine the anti-cancer effects of the combined therapy. In addition, the HPV E7 and RB1 expressions were measured by western blot analysis. Results: Results showed that the combined therapy induced about two times more apoptosis than that of ZFNs alone in SiHa and HeLa cells, and much more inhibition of cell viability than either of the separate treatment. The colony formation ability was inhibited more than 80% by the co-treatment, the protein expression of HPV16/18E7 was down regulated and that of RB1 was elevated. In addition, the xenografts experiment showed a synergistic effect between DDP and TSA together with ZFNs. Conclusion: Our results demonstrated that ZFNs combined with DDP or TSA functioned effectively in cervical cancer cells, and it provided novel ideas for the prevention and treatment of HPV-related cervical malignancies.

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Synthesis of 1-[(Aryl)(3-amino-5-oxopyrazolidin-4-ylidene) methyl]-2-oxo-1,2-dihydroquinoline-3-carboxylic Acid Derivatives and Their Breast Anticancer Activity

Crystals ◽

10.3390/cryst11050571 ◽

2021 ◽

Vol 11 (5) ◽

pp. 571

Author(s):

Ahmed Gaber ◽

Walaa F. Alsanie ◽

Majid Alhomrani ◽

Abdulhakeem S. Alamri ◽

Ibrahim M. El-Deen ◽

...

Keyword(s):

Breast Cancer ◽

Carboxylic Acid ◽

Anticancer Activity ◽

Cell Line ◽

Mtt Assay ◽

Analytical Techniques ◽

Anticancer Effect ◽

Reference Compound ◽

Anticancer Effects ◽

Mcf 7

This research aimed to produce new 1-[(aryl)(3-amino-5-oxopyrazolidin-4-ylidene) methyl]-2-oxo-1,2-dihydroquinoline-3-carboxylic acid derivatives and check their anticancer effect against the breast cancer MCF-7 cell line. The 2-oxo-1,2-dihydroquinoline-3-carboxylic acid (4) compound was obtained by hydrolyzing ethyl 2-oxo-1,2-dihydroquinoline-3-carboxylate (2) with thiourea and anhydrous potassium carbonate ethanol, which was then treated with ethyl 3-substituted 2-cyanoacrylates (6) in the presence of triethylamine in diethyl formamide to give 1-[2-(ethoxy)carbonyl-2-cyano-1-arylvinyl]-2-oxo-1,2-dihydroquinoline-3-carboxylic (7a,d). Cyclization of compound 7 with hydrazine hydrate ethanol inferred the association of 1-[(aryl)(3 amino-5-oxopyrazolidin-4-ylidene)methyl-2-oxo-1,2-dihydroquinol-3-carboxylates (8a,d). Spectroscopic and micro-analytical techniques such as IR, NMR, and elemental analysis were used to validate the structure of the synthesized organic compounds. The anticancer effects of the synthesized compounds 7a–d and 8a–d were tested by using the MTT assay on the MCF-7 cell line. When compared to the reference compound Dox, the compounds 7b, 7c, 8a, 8b, and 8c demonstrated strong anticancer activity against the MCF-7 cell line. The anticancer effects of the synthesized compounds 7a–d and 8a–d were tested against the MCF-7 cell line, using MTT assay. The compounds 7b, 7c, 8a, 8b, and 8c showed significant anticancer activity compared to the reference compound Dox against the MCF-7 cell line.

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