China
Africa
Explore chapters and articles related to this topic
Testicular germ cell apoptosis and spermatogenesis
Published in Rajender Singh, Molecular Signaling in Spermatogenesis and Male Infertility, 2019
Caspases are the initiators and executioners of apoptosis. They are synthesized in the form of procaspases, which get activated during the apoptotic process (73). These procaspases contain three domains: an NH2 domain and the p20 and p10 domains. Caspases are cysteine proteases that cleave their substrate protein after the aspartic acid residue that leads to cell death (45). The executioner caspases exist in the cytosol in the form of inactive dimers, and their activation is carried out by the initiator caspases through proteolytic cleavage of its catalytic domain to an active scaffold. The proteolytic cleavage allows the rearrangement of its mobile loop conferring it the catalytic activity (74,75). In the cytosol, caspase-3 and caspase-7 exist in their dimeric forms, and activation is through the cleavage within their respective linker segments (76). In human testis biopsies, effector caspase-7 seemed to be absent from normal human testes, whereas procaspase-3 and procaspase-6 were detected in germ cells. Increased germ cell apoptosis in patients with the spermatogenic arrest was associated with increased levels of active caspase-3, which indicates that caspase-3 is the major executioner of apoptosis in human infertility (77). Similarly, in rodents also caspase-3 appears to be the major executioner of apoptosis (78,79).
Immunomodulatory Activities of Silver Nanoparticles (AgNPs) in Human Neutrophils
Published in Huiliang Cao, Silver Nanoparticles for Antibacterial Devices, 2017
We then performed another study using smaller AgNPs with a diameter of 15 nm, AgNP15. Similarly to AgNP20, AgNP15 were found to rapidly penetrate human PMNs (Liz et al. 2015). However, AgNP15 appears to induce unconventional apoptosis. Indeed, in contrast to the cell shrinkage and CD16 cell surface shedding (Dransfield et al. 1994) normally observed in human apoptotic PMNs that we routinely used in our laboratory as markers of apoptotic cells, we rather observed that AgNP15 increase the cell volume and do not induce CD16 shedding. This unconventional cell death was clearly distinct from cell necrosis and was reversed by the addition of a pan-caspase inhibitor known to mostly inhibit caspase-1, caspase-3, caspase-4 and caspase-7. Because of this, and since we previously published that the ER stress-induced cell apoptotic pathway was operational in human PMNs, including the fact that these cells were also found to express caspase-4 and that it could be activated (Binet et al. 2010), we then tried to inhibit AgNP15-induced atypical cell death by adding specific inhibitors to caspase-1 and to caspase-4. Interestingly, both of these inhibitors were found to prevent the effect of AgNP15. Knowing that these two inflammatory caspases are known to be involved in inflammasome activation and IL-1β production (Fernandes-Alnemri et al. 2007; Man and Kanneganti 2015), it was logical to verify if AgNP15 increase the IL-1β production and, if so, to determine if caspase-1 or caspase-4 is involved. We found that, indeed, AgNP15 increased the neutrophil IL-1β production and that both caspases are involved, although caspase-4 is more importantly implicated (Liz et al. 2015). In this study, we also demonstrated that AgNP15 increased ROS production and that ROS participate in AgNP15-induced cell death. Finally, we reported in this study that when PMNs were forced to adhere, AgNP15 induced the NET formation.
Current and Future Perspectives of Marine Drugs for Cancer Disorders: A Critical Review
Published in Rohit Dutt, Anil K. Sharma, Raj K. Keservani, Vandana Garg, Promising Drug Molecules of Natural Origin, 2020
Bhaskaran Mahendran, Thirumalaraju Vaishnavi, Vishakante Gowda, Johurul Islam, Narahari Rishitha, Arunachalam Muthuraman, Rajavel Varatharajan
Seaweeds are the main sources of vitamins, iodine, protein, and minerals. The metabolites of seaweeds have a promising role in treating cancer cell proliferation. In addition, Halimeda sp. (Chlorophyceae) has a large number of polyphenols like catechin, epicatechin, epigallocatechin gallate, and gallic acid. These compounds are documented to the shown antioxidant, anti-tumor, and immunomodulating actions (Bocanegra et al., 2009). Further, edible seaweed, i.e., Palmaria palmate produces the anticancer activity with reduction of oxidative stress. The alcoholic extract of Acanthophora spicifera (red algae) inhibits the growth of Ehrlich’s ascites carcinoma cells. This report is similar to that of 5-fluorouracil treatment. Therefore, it considers as anti-cancer agents. Similarly, various marine algae like Ulva reticulata, Gracilariaf oliifera, and Padina boergesenii are reported to produce cytotoxic action (Patra and Muthuraman, 2013). Moreover, it also produces the anticancer action on adenocarcinoma cell via immunomodulatory action. The low-molecular-weight fucoidan of Ascophyllum nodosum also reported to produces the anti-proliferative effect on malignant and normal cells like fibroblasts, sigmoid colon adenocarcinoma cells, and smooth muscle cells via antitumor, anticancer, antimetastatic, and fibrinolytic action (Huang and Pardee, 1999). Furthermore, a variously isolated compound of marine algae, i.e., stylopoldione from Stypodium sp.; and condriamide-A from the Chondria sp. have produced the cytotoxic effect in colorectal cancer cells and human nasopharyngeal (Sung et al., 2005). In addition, caulerpenyne from Caulerpa sp.; meroterpenes and usneoidone from Cystophora sp.; eckol, phlorofucofuroeckol A, dieckol, and 8,8–bieckol of brown alga (Eisenia bicyclis) also produced the anticancer, antitumor, and anti-proliferating effects (Popovich and Kitts, 2004). Further, these compounds possess the various molecular mechanisms for an anticancer activity like modulation of apoptotic activity via caspase-7, caspase-8, Bax, Bcl-xL, and poly (ADP-ribose) polymerase (PARP). PARP is inducers of apoptosis of cancer cells via DNA cleavage (Elmore, 2007). However, the large exposure and clinical evidence remain to be explored. Further, seaweeds reduce the higher level of potassium in plasma leads to prevent the abnormalities of blood pressure (Srinath Reddy and Katan, 2004). Clinically, the seaweed-derived alginic acid is producing the glucose-lowering effects in diabetic patients. The dietary fibers of seaweed reported on antioxidant, anti-mutagenic, anticoagulant, and antitumor activities. In addition, it also plays an important role in the modification of lipid metabolism and protein modification in the cancer cell.
Edible Tuber Amorphophallus paeoniifolius (Dennst.) Extract Induces Apoptosis and Suppresses Migration of Breast Cancer Cells
Published in Nutrition and Cancer, 2021
Munmi Majumder, Manoj Sharma, Siddhartha Maiti, Rupak Mukhopadhyay
Induction of apoptosis is a possible mode of cell death in cancer cells. Treatment of APTE induced significant apoptosis in both MCF-7 and MDA-MB-231 cells. Dose-dependent increase of pro-apoptotic BAX and inhibition of antiapoptotic BCL-2 indicated induction of apoptosis by the extract. BAX is a key component for apoptosis via mitochondrial stress and increases membrane’s permeability. This results in the release of cytochrome c from mitochondria and initiation of CASPASE activation pathway for apoptosis. There are reports that demonsrtrate p53-mediated induction of BAX. However, APTE treatment did not induce p53 expression suggesting BAX activation in this case might be independent of p53 (35). The expression of CASPASE-7 is a major contributor to the execution of apoptosis. It is cleaved by different enzymes whose expressions are upregulated during apoptosis. The activated CASPASE-7 is responsible for cleavage of many substrates, including PARP. APTE successfully induced CASPASE-7 activation leading to cleavage of PARP in experimental cells (36). These observations suggest that APTE induces apoptosis in both MCF-7 and MDA-MB-231 cells possibly by a CASPASE-7 dependent pathway (37).
Chemopreventive effect of α-hederin/carboplatin combination against experimental colon hyperplasia and impact on JNK signaling
Published in Toxicology Mechanisms and Methods, 2021
Hoda I. Bahr, Afaf T. Ibrahiem, Attia M. Gabr, Alaaeldeen M. Elbahaie, Hoda S. Elmahdi, Nema Soliman, Amal M. Youssef, Mohamed El-Sherbiny, Sawsan A. Zaitone
The current results indicated that caspase 3 was increased in mice treated with carboplatin or carboplatin + α-hederin. Actually, apoptosis is involved in the development, maintenance and tissue homeostasis involving activation of caspase 3 and caspase 7 and is recognized as a target for chemopreventive therapies (Jan and Chaudhry 2019). Also, treatment of breast cancer cells with 2 μg/ml α-hederin for 24 h promoted apoptosis via interfering with mitochondrial potential and subsequently caspase 9 and caspase 3 activation (Cheng et al. 2014). Recently, α-hederin has been exhibited anti-proliferative impact in cisplatin-resistant gastric cancer cells via elevating ROS production with depletion in GSH activating caspase pathway in vitro (HGC27/DDP) and in vivo (Liu Y et al. 2019). Further, α-hederin can impede proliferation and trigger apoptosis of SCC-25 cells via suppression of PI3K/AKT/mTOR signaling pathway with upregulating caspase 3 and 9 activities (Wang H et al. 2019).
In vitro evaluation of Annona muricata L. (Soursop) leaf methanol extracts on inhibition of tumorigenicity and metastasis of breast cancer cells
Published in Biomarkers, 2020
Aditi Venkatesh Naik, Krishnan Sellappan
Intensive molecular studies to date have shown that there are two key apoptotic pathways, namely extrinsic through a death receptor and intrinsic caspase triggered mitochondrial-mediated pathways. The intrinsic cytochrome c pathway stimulates the caspase-9 while the extrinsic route stimulates the caspase-8. Unless these initiator caspases are activated, the apoptosis execution process is triggered via caspase-7,-6 and-3 activation. Expression of caspase protease is the premise of cell apoptosis, and further activation of caspase-3 in the apoptotic mechanism is a crucial downstream effect (Moghadamtousi et al.2014, 2015b). Our results showed that treatment with LMAM elevated caspase-3 activities. It is thus postulated that apoptosis activation is through a mitochondrial-mediated cascade in the breast cancer cells notably closely related to the occurrence of bioactive components in A. muricata extracts namely potent alkaloids, phenols, flavonoids, and acetogenins (ACG) (Pieme et al.2014, George et al.2015, Abdullah et al.2017, Syed Najmuddin et al.2017).