scholarly journals New Diterpenoids from Mesona procumbens with Antiproliferative Activities Modulate Cell Cycle Arrest and Apoptosis in Human Leukemia Cancer Cells

2021 ◽  
Vol 14 (11) ◽  
pp. 1108
Author(s):  
Hung-Tse Huang ◽  
Chia-Ching Liaw ◽  
Yu-Chi Lin ◽  
Geng-You Liao ◽  
Chih-Hua Chao ◽  
...  

Mesona procumbens is a popular material used in foods and herbal medicines in Asia for clearing heat and resolving toxins. However, phytochemical research on this plant is very rare. In this study, eleven new diterpenoids, mesonols A-K (1–11), comprising seven ent-kauranes, three ent-atisanes, and one sarcopetalane, were isolated from its methanolic extract. Structural elucidation of compounds 1–11 was performed by spectroscopic methods, especially 2D NMR, HRESIMS, and X-ray crystallographic analysis. All isolates were assessed for their antiproliferative activity, and compounds 1-4 showed potential antiproliferative activities against A549, Hep-3B, PC-3, HT29, and U937 cancer cells, with IC50 values ranging from 1.97 to 19.86 µM. The most active compounds, 1 and 2, were selected for further investigation of their effects on cell cycle progression, apoptosis, and ROS generation in U937 human leukemia cancer cells. Interestingly, it was found that compounds 1 and 2 induced antiproliferative effects in U937 cells through different mechanisms. Compound 1 caused cell cycle arrest at the G2/M phase and subsequent cell death in a dose- and time-dependent manner. However, 2-mediated antiproliferation of U937 cells triggered ROS-mediated mitochondrial-dependent apoptosis. These results provide insight into the molecular mechanism involved in the antiproliferative activities of compounds 1 and 2 in U937 cells. Altogether, the study showed that new diterpenoid compounds 1 and 2 from M. procumbens are potent and promising anticancer agents.

2017 ◽  
Vol 38 (3) ◽  
pp. 1783-1789 ◽  
Author(s):  
Na Lam Hwang ◽  
Yong Jung Kang ◽  
Bokyung Sung ◽  
Seong Yeon Hwang ◽  
Jung Yoon Jang ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Zheng-hua Fei ◽  
Kan Wu ◽  
Yun-liang Chen ◽  
Bing Wang ◽  
Shi-rong Zhang ◽  
...  

Several data has reported that capilliposide, extracted from a traditional Chinese medicine,Lysimachia capillipesHemsl. (LC) could exhibit inhibitory effect on cell proliferation in various cancers. The current study investigated the antitumor efficacy ofCapilliposideand elucidated its potential molecular mechanism involved in vivo and vitro. Our results indicated that LC capilliposide inhibited proliferation of lung cancer cells in a dose-dependent manner. LC capilliposide induced cell cycle arrest at the S stage and enhanced apoptosis in NSCLC cells. Treatment with LC capilliposide increased the intracellular level of ROS, which activated the mitochondrial apoptotic pathway. Blockage of ROS by NAC highly reversed the effect of LC capilliposide on apoptosis. Xenograft tumor growth was significantly lower in the LC-treated group compared with the untreated control group(P<0.05). The results also show that LC treatment does not produce any overt signs of acute toxicity in vivo. These findings demonstrate that LC capilliposide could exert an anti-tumor effect on NSCLC through mitochondrial-mediated apoptotic pathway and the activation of ROS is involved.


Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 1043 ◽  
Author(s):  
Ho Lee ◽  
Venu Venkatarame Gowda Saralamma ◽  
Seong Kim ◽  
Sang Ha ◽  
Suchismita Raha ◽  
...  

Pectolinarigenin (PEC), a natural flavonoid present in Cirsium chanroenicum and in some species of Citrus fruits, has various pharmacological benefits such as anti-inflammatory and anti-cancer activities. In the present study, we investigated the anti-cancer mechanism of PEC induced cell death caused by autophagy and apoptosis in AGS and MKN28 human gastric cancer cells. The PEC treatment significantly inhibited the AGS and MKN28 cell growth in a dose-dependent manner. Further, PEC significantly elevated sub-G1 phase in AGS cells and G2/M phase cell cycle arrest in both AGS and MKN28 cells. Apoptosis was confirmed by Annexin V and Hoechst 33342 fluorescent staining. Moreover, Immunoblotting results revealed that PEC treatment down-regulated the inhibitor of apoptosis protein (IAP) family protein XIAP that leads to the activation of caspase-3 thereby cleavage of PARP (poly-ADP-ribose polymerase) in both AGS and MKN28 cells in a dose-dependent manner. The autophagy-inducing effect was indicated by the increased formation of acidic vesicular organelles (AVOs) and increased protein levels of LC3-II conversion in both AGS and MKN28 cells. PEC shows the down regulation of PI3K/AKT/mTOR pathway which is a major regulator of autophagic and apoptotic cell death in cancer cells that leads to the down-regulation of p-4EBP1, p-p70S6K, and p-eIF4E in PEC treated cells when compared with the untreated cells. In conclusion, PEC treatment might have anti-cancer effect by down-regulation of PI3K/AKT/mTOR pathway leading to G2/M phase cell cycle arrest, autophagic and apoptotic cell death in human gastric cancer cells. Further studies of PEC treatment can support to develop as a potential alternative therapeutic agent for human gastric carcinoma.


2020 ◽  
Vol 20 (13) ◽  
pp. 1530-1537 ◽  
Author(s):  
Santhosh Arul ◽  
Harinee Rajagopalan ◽  
Jivitesh Ravi ◽  
Haripriya Dayalan

Background: Ovarian cancer is the fifth most common cause of cancer deaths among women with lesser prognostics. Current treatment options are chemotherapy with platinum and taxane based chemotherapy. β-Caryophyllene (BCP) an essential oil found in many plant species is known to possess an anti-proliferative effect. Objective: We aimed to investigate the antiproliferative, cytotoxic, and apoptotic role of BCP against ovarian cancer cells PA-1 and OAW 42. Methods: The antiproliferative effect of BCP was determined by MTT assay and cell viability by trypan blue exclusion assay. Cell cycle and live/dead cell analyses were performed by flow cytometry to determine cell cycle distribution and apoptosis, respectively. Results: Results of MTT assay proved the anti-proliferative effect of BCP in a dose and time-dependent manner in ovarian cancer cells. Cell cycle analysis showed that BCP induced S Phase arrest in OAW 42 cells. Results of apoptosis assay confirmed the apoptosis inducing potential of BCP in ovarian cancer cells. The apoptosis is mediated by caspase-3 activation and PARP cleavage. Conclusion: The results of our present study prove that BCP exerts its action partly by inducing cell cycle arrest and apoptosis in ovarian cancer. We conclude that BCP is a potential anti-cancer agent.


2016 ◽  
Vol 11 (2) ◽  
pp. 478 ◽  
Author(s):  
Fu-Hua Zhang ◽  
Yu-Ling Yan ◽  
Ying Wang ◽  
Zhen Liu

<p class="Abstract">The main purpose of the present study was to examine the antitumor and apoptotic effects of lactucin in HL-60 human leukemia cancer cells. MTT assay was used to examine the cytotoxic effects of lactucin while as phase contrast, fluorescence and transmission electron microscopy techniques were used to evaluate the apoptotic effects of lactucin in these cells. Flow cytometry was used to assess the effects of lactucin on cell cycle phase distribution. The results indicate that lactucin induced potent, time– and dose-dependent antitumor effects. The microscopic techniques showed that lactucin induced characteristic features of apoptosis including cell shrinkage, membrane blebbing, appearance of vacuoles, swelling of mitochondria and endoplasmic reticulum. Viable cells are stained green, early apoptotic cells are stained yellow, while as late apoptotic cells are stained reddish orange. Flow cytometry revealed that lactucin induced sub-G1 cell cycle arrest.</p><p class="Abstract"><strong>Video Clips</strong></p><p class="Abstract">Phase contrast microscopy:  <a href="https://www.youtube.com/v/xrTjOVvlTxQ">1</a>  <a href="https://www.youtube.com/v/GxuMkGnkpSE">2</a>  <a href="https://www.youtube.com/v/SfmdL2-O45Y">3</a>  <a href="https://www.youtube.com/v/7vbJ9HMRTHU">4</a>  <a href="https://www.youtube.com/v/u4aLzmlXF8s">5</a>  <a href="https://www.youtube.com/v/ucl8DjPeV9c">6</a>  <a href="https://www.youtube.com/v/uI932TJVfFY">7</a>  <a href="https://www.youtube.com/v/5sMlUKbKMhc">8</a>  <a href="https://www.youtube.com/v/-tx20gFHYnc">9</a></p><p> </p>


2020 ◽  
Author(s):  
Aiai Ma ◽  
Xinge Qi ◽  
Kan Jiang ◽  
Bin Chen ◽  
Junlin Liu ◽  
...  

Abstract Background: Endophytic actinomycetes, as emerging sources of bioactive metabolites, play a vital role in pharmaceutical development. Recent reports demonstrated that endophytic Streptomyces isolates could yield compounds with potent anticancer and antimicrobial properties that may be developed into chemotherapeutic drugs. Our study displayed that Streptomyces sp. LRE541 obtained from the root tissues of Lilium davidii var. unicolor Cotton, could be a potential source of anticarcinogens and antimicrobials.Results: Isolate LRE541 was characterized and identified as belonging to the genus Streptomyces based on the 16S rDNA sequence analysis, with highest sequence similarity to Streptomyces tauricus JCM4837T (98.81%). It produced extensively branched red substrate and vivid pink aerial hyphae that changed into amaranth, with elliptic spores sessile to the aerial mycelia. The secondary metabolites (EtOAc extract) produced by isolate LRE541 exhibited significant anticancer activities with IC50 values of 0.021, 0.2904, 1.484, 4.861, 6.986, 8.106, 10.87, 12.98, and 16.94 μg/mL against cancer cells RKO, 7901, HepG2, CAL-27, MCF-7, K562, Hela, SW1190 and A549, respectively, evaluated by the MTT assay. In contrast, the EtOAc extract showed less cytotoxicity activity against the normal human pulmonary artery endothelial cell (HPAEC) with an IC50 value of > 20 μg/mL than that of the cancer cells. To further explore the mechanism underlying the decrease in viability of cancer cells following the EtOAc extract treatment, cell apoptosis and cell cycle arrest assays were performed using two cancer cell lines, RKO and 7901. The result demonstrated that the EtOAc extract inhibited cell proliferation of RKO and 7901 cells by causing cell cycle arrest both at the S phase and inducing apoptosis in a dose‑dependent manner. Moreover, the EtOAc extract of isolate LRE541 with the concentrations within 100 μg/mL also possessed the antagonistic activities against E. coli ATCC 25922, MRSA ATCC 25923, P. aeruginosa and C. albicans ATCC 66415, and the antagonistic potent against the tested pathogens all displayed a dose-dependent manner. The UHPLC-MS/MS analysis of the EtOAc extract revealed that the presence of antitumor, potential antitumor and antimicrobial compounds could account for the potent antineoplasmic and antagonistic properties of the extract. Conclusion: This study provides the potential therapeutic applications of the bioactive metabolites from Streptomyces sp. LRE541 as novel antimicrobial and anticancer agents.


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