scholarly journals Emodin, isolated and characterized from an endophytic fungus Polyporales sp., induces apoptotic cell death in human lung cancer cells through the loss of mitochondrial membrane potential

2017 ◽  
Vol 6 (5) ◽  
pp. 288-292
Author(s):  
Refaz Ahmad Dar ◽  
◽  
Rabiya Majeed ◽  
Abid Ali sheikh ◽  
Shakeel-u Rehman ◽  
...  

Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a Chinese herbal anthraquinone that exhibits numerous biological activities, such as antitumor, antibacterial, antiinflammatory, and immunosuppressive. From an endophytic fungus, a close relative of Polyporales sp., found in association with Rheum emodi, Wall. ex Meissn a compound (Rz) was isolated and characterizedby different spectroscopic techniques (1H-NMR, 13CNMR, 2D-NMR, and HRMS). The compound (Rz) displayed a range of cytotoxicities against different human cancer cell lines like THP-1(Leukemia), A549 (Lung), NCI-H322 (lung) and Colo-205(colon) at a concentration of 70 and 100 µM. The compound had strong anticancer activity by arresting the cell cycle at G1 and G2/M phase and loss of mitochondrial membrane potential in A-549 lung cancer cells in concentration dependent manner. The study suggests that emodin induced anticancer effects may have novel therapeutic applications for the treatment of lung cancer.

Author(s):  
Konstantin Komoshvili ◽  
Tzippi Beker ◽  
Jacob Levitan ◽  
Asher Yahalom ◽  
Ayan Barbora ◽  
...  

Efficiently targeted cancer therapy without causing detrimental side effects is necessary for alleviating patient care and improving survival rates. This paper presents observations of morphological changes in H1299 human lung cancer cells following MMW irradiation (75 – 105 GHz) at a non-thermal power density of 0.2 mW/cm2, investigated over 14 days of subsequent physiological incubation following exposure. Microscopic analyses of physical parameters measured indicate MMW irradiation induces significant morphological changes characteristic of apoptosis and senescence. The Immediate short-term stress responses translate into long-term effects, retained over the duration of the experiment(s); reminiscent of the phenomenon of Accelerated Cellular Senescence (ACS) achieving terminal tumorigenic cell growth. Further, results were observed to be treatment-specific in energy (dose) dependent manner and were achieved without the use of chemotherapeutic agents, ionizing radiation or thermal ablation employed in conventional methods; thereby overcome associated side effects. Adaptation of the experimental parameters of this study in clinical oncology concomitant with current developmental trends of non-invasive medical endoscopy alleviates MMW therapy as an effective treatment procedure for human non-small cell lung cancer (NSLC)


2020 ◽  
pp. jbc.RA120.015188
Author(s):  
Daniela Volonte ◽  
Morgan Sedorovitz ◽  
Victoria E. Cespedes ◽  
Maria L. Beecher ◽  
Ferruccio Galbiati

Oncogenic K-Ras (K-RasG12V) promotes senescence in normal cells but fuels transformation of cancer cells after the senescence barrier is bypassed. The mechanisms regulating this pleiotropic function of K-Ras remain to be fully established and bear high pathological significance. We find that K-RasG12V activates the angiotensinogen (AGT) gene promoter and promotes AGT protein expression in a Kruppel Like Factor 6 (KLF6)-dependent manner in normal cells. We show that AGT is then converted to angiotensin II (Ang II) in a cell-autonomous manner by cellular proteases. We show that blockade of the Ang II receptor type 1 (AT1-R) in normal cells inhibits oncogene-induced senescence (OIS). We provide evidence that the oncogenic K-Ras-induced synthesis of Ang II and AT1-R activation promote senescence through caveolin-1-dependent and NOX2-mediated oxidative stress. Interestingly, we find that expression of AGT remains elevated in lung cancer cells but in a KLF6-independent and High Mobility Group AT-Hook 1 (HMGA1)-dependent manner. We show that Ang II-mediated activation of the AT1-R promotes cell proliferation and anchorage-independent growth of lung cancer cells through a STAT3-dependent pathway. Finally, we find that expression of AGT is elevated in lung tumors of K-RasLA2-G12D mice, a mouse model of lung cancer, and human lung cancer. Treatment with the AT1-R antagonist losartan inhibits lung tumor formation in K-RasLA2-G12D mice. Together, our data provide evidence of the existence of a novel cell-autonomous and pleiotropic Ang II-dependent signaling pathway through which oncogenic K-Ras promotes OIS in normal cells while fueling transformation in cancer cells.


2001 ◽  
Vol 412 (1) ◽  
pp. 13-20 ◽  
Author(s):  
H.Christian Weber ◽  
James Walters ◽  
Julius Leyton ◽  
Marchessini Casibang ◽  
Sally Purdom ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Arpasinee Sanuphan ◽  
Preedakorn Chunhacha ◽  
Varisa Pongrakhananon ◽  
Pithi Chanvorachote

Nitric oxide (NO) found in the vicinity of lung cancer cells may play a role in the regulation of cancer cell behaviors. To explore the possible effects of NO on cell motility, human lung cancer cells were exposed to nontoxic concentrations of NO for 0–14 days, and the migratory characteristics of the cells were determined. The present study found that long-term treatment with NO significantly enhanced cell migration in a dose- and time-dependent manner. Furthermore, we found that the increased migratory action was associated with the increased expression of caveolin-1 (Cav-1), which in turn activated the focal adhesion kinase (FAK) and ATP-dependent tyrosine kinase (Akt) pathways. Notably, the NO-treated cells exhibited an increased number of filopodia per cell, as well as an increase in the levels of cell division cycle 42 (Cdc42) protein. Together, these results indicate that extended NO exposure has a novel effect on cell migration through a Cav-1-dependent mechanism, a finding that strengthens our understanding of cancer biology.


Author(s):  
Konstantin Komoshvili ◽  
Tzippi Becker ◽  
Jacob Levitan ◽  
Asher Yahalom ◽  
Ayan Barbora ◽  
...  

Efficiently targeted cancer therapy without causing detrimental side effects is necessary for alleviating patient care and improving survival rates. This paper presents observations of morphological changes in H1299 human lung cancer cells following W-band MMW irradiation (75 – 105 GHz) at a non-thermal power density of 0.2 mW/cm2, investigated over 14 days of subsequent physiological incubation following exposure. Microscopic analyses of physical parameters measured indicate MMW irradiation induces significant morphological changes characteristic of apoptosis and senescence. The Immediate short-term responses translate into long-term effects, retained over the duration of the experiment(s); reminiscent of the phenomenon of Accelerated Cellular Senescence (ACS) achieving terminal tumorigenic cell growth. Further, results were observed to be treatment-specific in energy (dose) dependent manner and were achieved without the use of chemotherapeutic agents, ionizing radiation or thermal ablation employed in conventional methods; thereby overcoming associated side effects. Adaptation of the experimental parameters of this study for clinical oncology concomitant with current developmental trends of non-invasive medical endoscopy alleviates MMW therapy as an effective treatment procedure for human non-small cell lung cancer (NSCLC).


2020 ◽  
Vol 19 (9) ◽  
pp. 1835-1842
Author(s):  
Supita Tanasawet ◽  
Wanida Sukketsiri ◽  
Pennapa Chonpathompikunlert ◽  
Pennapa Chonpathompikunlert ◽  
Wanwimol Klaypradit ◽  
...  

Purpose: To investigate the anti-cancer potential of astaxanthin from Litopenaeus vannamei encapsulated in liposomes (ASX) to treat lung cancer A549 cells.Methods: Lung adenocarcinoma A549 cells were cultured and treated with ASX, following which cell viability and nuclear staining were performed. Generation of ROS was identified by the DCFH-DA assay while tetramethylrhodamine ethyl ester was used to determine the mitochondrial membrane potential. Flow cytometry was applied to investigate caspase-3/7 activity and cell cycle distribution.Results: ASX inhibited growth of A549 in a concentration- and time- dependent manner. The IC50 values at 24, 48 and 72 h were 53.73, 22.85, 17.46 μg/mL, respectively (p < 0.05). After incubation with ASX, the morphological changes were observed in A549 cells following Hoechst 33342/PI fluorescent staining. ASX increased ROS generation and was associated with the collapse of mitochondrial membrane potential, which subsequently triggered the activation of caspase-3/7 activity leading to apoptosis (p < 0.05). In addition, A549 cells accumulated in the G0/G1 phase.Conclusion: The results suggest that ASX is a valuable nutraceutical agent to target A549 lung cancer cells via ROS-dependent pathway as well as blockage of cell cycle progression. Keywords: Astaxanthin, Litopenaeus vannamei, Lung cancer, A549, Apoptosis


2020 ◽  
Author(s):  
Ziyu Cheng ◽  
Zhihui Li ◽  
Ling Gu ◽  
Liqiu Li ◽  
Qian Gao ◽  
...  

Abstract Background: Drug resistance has become the main reason for the failure of tumor chemotherapy. In our previous study, ophiopogonin B (OP-B) has been verified to inhibit cell proliferation in numerous non-small cell lung cancer (NSCLC) cells. However, it is still unknown whether it can improve the drug resistance of lung cancer cells. Herein, we compared the inhibition effects of OP-B on NCI-H460, A549, A549/DDP and A549/PTX cells, and tried to find out the most sensible cell line to OP-B and the underlying reasons. Methods: The sensitivity of NCI-H460, A549, A549/DDP, and A549/PTX cells to OP-B was determined by CCK-8 assay, and the results were further verified in orthotopic tumor nude mice model and zebrafish tumor model. To identify pyroptosis in the cells, electron microscopy was used to observe cell morphology, flow cytometry was used to detect the mitochondrial membrane potential, and the LDH release rate was analyzed by microplate reader. Otherwise, immunofluorescence and immunohistochemical staining assay, western blot and qRT-PCR were used for detection of pyroptosis-correlated pathway.Results: In vitro, A549/DDP cell was verified to be most sensitive to OP-B than NCI-H460, A549, or A549/PTX cells. In vivo, OP-B inhibited the growth of A549/DDP orthotopic tumor more significantly than that of A549 both in nude mice and zebrafish models. Cell morphological feature, mitochondrial membrane potential, LDH release rate, production of IL-1β and expression of Caspase-1/GSDMD all showed that pyroptosis happened more significantly in A549/DDP cells than that in A549 cells after OP-B treatment.Conclusion: Though inducing more significantly pyroptosis by activating Caspase-1/GSDMD pathway, OP-B relieved DDP resistance of A549 cells.


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