DNA binding, artificial nuclease activity and cytotoxic studies of newly synthesized steroidal pyrimidines

Dar, Ayaz Mahmood; Rah, Bilal; Mir, Shafia; Nabi, Rizwan; Shamsuzzaman, _; Gatoo, Manzoor Ahmad; Mashrai, Ashraf; Khan, Yusuf

doi:10.1016/j.ijbiomac.2017.12.128

Cited by 16 publications

(8 citation statements)

References 43 publications

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“…Anticancer drugs kill tumor malignant cells mainly by apoptosis as well as trigger cell cycle arrest to attenuate the tumor cell growth (Zilla et al, 2014;Dar et al, 2018;Alnuqaydan et al, 2020). Luo and others (Luo et al, 2018) showed that a 6-Gingerol promotes apoptosis and subsequently triggers cell cycle arrest of gastric carcinoma cells to reduce the growth of malignant cells (Luo et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Artemisinin potentiates apoptosis and triggers cell cycle arrest to attenuate malignant growth of salivary gland tumor cells

et al. 2022

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One of the rare malignant tumors developing within the glands of the buccal cavity in human beings is salivary gland tumors (SGTs). The hallmark of SGTs is the fusion of nuclear factor IB (NFIB) and myeloblastosis (MYB) genes developed after the translocation of q22-23; p23-24. Although the aetiology of SGTs is not clear, however, the therapeutic modalities are surgical resection followed by the combination of chemotherapy and radiotherapy if a chance of recurrence seems to develop. Owing to have numerous side effects of chemotherapy, the drug development has been shifted to natural products with minimal side effects. One of the key phytochemical artemisinin derived from wormwood Artemisia annua exhibits various pharmacological activities against various in-vivo and in-vitro cellular models. Here, we evaluated the cytotoxic potential of artemisinin against A-253 cells with possible underlying cell death mechanisms. Our results showed that artemisinin reduces the proliferation of cells in a concentration-dependent manner and displays IC50 value in a range of 10.23, 14.21 μM, and 203.18 μM against A-253/HTB-41 and transformed salivary gland SMIE cells, respectively. Flow cytometry analysis demonstrated that artemisinin promotes a significant amount of apoptotic cellular population and triggers G0/G1 arrest of A-253 cells in a concentration-dependent manner. To verify the mechanism of cell death induced by artemisinin in A-253 cells, we found an increased level of Bax, Bim, Bad, Bak and reduced level of antiapoptotic protein Bcl-2, Bcl-XL with concomitant release of mitochondrial resident protein cytochrome c into the cytoplasm. Additionally, we found that artemisinin augments the production of reactive oxygen species which further leads to the activation of proapoptotic proteins PARP1, and caspase-3, in a concentration-dependent manner thereby triggering apoptosis. In conclusion, artemisinin exhibits promising anticancer therapeutic potential against A-253 cells and needs further validation of in-vitro results in preclinical models.

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Section: Discussionmentioning

confidence: 99%

Artemisinin potentiates apoptosis and triggers cell cycle arrest to attenuate malignant growth of salivary gland tumor cells

et al. 2022

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“…HCC (HepG2) cells (5·10 5 ) were seeded on coverslips in 30-mm Petri dishes and were exposed to different concentrations of plant methanolic extract for 24 h ( 29 ). After completion of the treatment, the cells were processed for phase-contrast microscope LSM-510 (Carl Zeiss, Munich, Germany) to detect the phenotypic changes in the morphology of the treated cells.…”

Section: Methodsmentioning

confidence: 99%

“…Next day the cells were processed for cell cycle analysis by incubating fixed cells with RNase (100 μg/mL) for 30 minutes at 37 °C and stained with PI (50 μg/mL) in the dark for another 30 min at 4 °C. The cell cycle analysis was done by using the BDTM LSRII (5•10 5) were seeded on coverslips in 30 mm Petri-dishes and were exposed to different concentrations of TA methanolic extract of for 24 h (24). After completion of the treatment period, cells were processed for phase-contrast microscope LSM-510 (Carl Zeiss, Germany) to detect the phenotypic changes in the morphology of treated cells.…”

Section: Cell Cycle Analysismentioning

confidence: 99%

Tamarix articulata Inhibits Cell Proliferation, Promotes Cell Death Mechanisms and Triggers G0/G1 Cell Cycle Arrest in Hepatocellular Carcinoma Cells

Alnuqaydan

2021

Food Technol. Biotechnol. (Online)

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Research background. From ancient times plants have been used for medicinal purposes against various ailments. In the modern era, plants are a major source of drugs and are an appealing drug candidate for the anticancer therapeutics against various molecular targets. Here we tested Tamarix articulata methanolic extract of dry leaves for anticancer activity against a panel of hepatocellular carcinoma cells. Experimental approach. Cell viability of hepatocellular carcinoma cells was determined by MTT assay after dose-dependent treatment with extract of Tamarix articulata. Phase-contrast microscopy and DAPI staining were performed to analyze cellular and nuclear morphology. Immunoblotting was performed to determine the expression of proteins associated with autophagy, apoptosis, and cell cycle. However, flow cytometry was used for the quantification of apoptotic cells and the analysis of cells in different phases of the cell cycle after treatment with varying doses of Tamarix articulata. Additionally, acridine orange staining and DCFHDA dye were used to analyze the quantification of autophagosomes and reactive oxygen species. Results and conclusion. Our results demonstrate that Tamarix articulata methanolic extract exhibits promising antiproliferative activity with IC50 values (271±4.38), (298±7.08) and (336±6.11) µg/mL against HepG2, Huh7D12, and Hep3B cell lines, respectively. Mechanistically, we found Tamarix articulata methanolic extract induces cell death by activating apoptosis and autophagy pathways. First, Tamarix articulata methanolic extract promotes autophagy which was confirmed by acridine orange staining. The immunoblotting analysis further confirms that Tamarix articulata methanolic extract consistently induces the conversion of, LC3I to LC3II form with a gradual decrease in expression of autophagy substrate protein p62 at higher doses. Second, Tamarix articulata methanolic extract promotes reactive oxygen species production in hepatocellular carcinoma cells and activates reactive oxygen species-mediated apoptosis. Flow cytometry and immunoblotting analysis showed that Tamarix articulata methanolic extract induces dose-dependent apoptosis and activates proapoptotic proteins caspase-3 and PARP1. Additionally, Tamarix articulata methanolic extract triggers the arrest of the G0/G1 phase of the cell cycle and upregulates the protein expression of p27/Kip, and p21/Cip, with a decrease in cyclin-D1 expression in hepatocellular carcinoma cells. Novelty and scientific contribution. The current study demonstrates that Tamarix articulata methanolic extract exhibits promising anticancer potential to kill tumor cells by programmed-cell-death type I and II mechanisms and could be explored for potential drug candidate molecules to curtail cancer in the future.

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“…The cells were cultured using the standard protocol as described previously (Dar et al, 2018). Briefly, lung adenocarcinoma cells were seeded in 96-well plates at 5×10 3 per well and incubated at 37°C in a 5% CO 2 incubator overnight to allow for a proper adhesion to the bottom surface of the plate.…”

Section: Cell Proliferation/cell Viability Assaymentioning

confidence: 99%

Histone demethylase KDM5A enhances cell proliferation, induces EMT in lung adenocarcinoma cells, and have a strong causal association with paclitaxel resistance

2021

Acta Biochim Pol

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Recent reports suggest that histone demethylase KDM5A emerges as a new player in the development of drug resistance and thus increases the challenges of chemotherapy. Here, we explore the role of KDM5A in cell proliferation, epithelial-mesenchymal transition (EMT)and its causal association with paclitaxel resistance in lung adenocarcinoma. Paclitaxel-resistant lung adenocarcinoma PTX-Calu-3 cells showed significantly higher IC50 value (7±0.176 µM) upon paclitaxel treatment than lung adenocarcinoma SK-LI-1 (3.6±0.005 nM), Calu-3 (4.3±0.015 nM), and A549 (4.5±0.106 nM) cells. We found that expression of KDM5A and P-glycoprotein (P-gp), which plays a critical role in the development of paclitaxel resistance, were significantly higher in PTX-Calu-3 cells compared to SK-LI-1, Calu-3, and A549 cells.. We observed a significant increase in the expression of mesenchymal markers N-cadherin and vimentin, and a concomitant decrease in expression of E-cadherin and α-catenin in PTX-Calu-3 compared to SK-LI-1, Calu-3, and A549 lung cancer cell lines. Transwell Boyden chamber and wound healing assays further demonstrated that a significantly higher number of PTX-Calu-3 cells were invasive and motile compared to SK-LI-1, Calu-3, and A549 cells, thus supporting the role of KDM5A in metastasis-associated processes. Additionally, a significantly higher expression of KDM5A was observed in lung adenocarcinoma patients’ samples compared with adjacent normal tissues as well as in PTX-Calu-3 cells compared toSK-LI-1, Calu-3, and A549 cells, as shown both with histochemistry and real time-polymerase chain reaction (RT-PCR). In summary, these results suggest that KDM5A plays a key role in lung adenocarcinoma by promoting proliferation, EMT, and drug resistance to paclitaxel treatment.

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DNA binding, artificial nuclease activity and cytotoxic studies of newly synthesized steroidal pyrimidines

Cited by 16 publications

References 43 publications

Artemisinin potentiates apoptosis and triggers cell cycle arrest to attenuate malignant growth of salivary gland tumor cells

Artemisinin potentiates apoptosis and triggers cell cycle arrest to attenuate malignant growth of salivary gland tumor cells

Tamarix articulata Inhibits Cell Proliferation, Promotes Cell Death Mechanisms and Triggers G0/G1 Cell Cycle Arrest in Hepatocellular Carcinoma Cells

Histone demethylase KDM5A enhances cell proliferation, induces EMT in lung adenocarcinoma cells, and have a strong causal association with paclitaxel resistance

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