China
Africa
Explore chapters and articles related to this topic
Herbs in Cancer Therapy
Published in Anil K. Sharma, Raj K. Keservani, Surya Prakash Gautam, Herbal Product Development, 2020
Annum Malik, Shahzadi Sidra Saleem, Kifayat Ullah Shah, Learn-Han Lee, Bey Hing Goh, Tahir Mehmood Khan
Vinorelbine and Vinblastine by phosphorylation cause Bcl-2 inactivation. This inactivation of Bcl-2 cause the basis for death of cancerous cells by apoptosis (Fan et al. 2000, Liu et al. 2001). Recently mitotic catastrophe has been described in which Vincristine induces cell death. This mode of cell death involves aberrant mitosis forming tetraploid non-viable cells containing multiple micronuclei (Darwiche et al. 2007). In response to Vincristine, the apoptosis resistant HL60-derived HCW-2 cell line underwent mitotic catastrophe, which led to the capase-3 activation and oligonucleosomal DNA degradation (Magalska et al. 2006). Campothecins induce cell death by upregulating proapoptotic genes and downregulating antiapoptotic genes (Darwiche et al. 2007). Apoptosis by Homoharringtonine is confirmed in several tumor types including leukemia, lymphoma, neuroblastoma and carcinoma (Borgne et al. 2006). Homoharringtonine (proliferation and protein inhibitor) may be more effective in resistant cancer when used in combination treatments with nucleoside analogs or mitosis inhibitors (Darwiche et al. 2007).
The Role of Nanoparticles in Cancer Therapy through Apoptosis Induction
Published in Hala Gali-Muhtasib, Racha Chouaib, Nanoparticle Drug Delivery Systems for Cancer Treatment, 2020
Marveh Rahmati, Saeid Amanpour, Hadiseh Mohammadpour
The superfamily of BCl-2 family proteins located in the mitochondrial membrane determines cell fate decisions (i.e., cell survival or death) by controlling MOMP. Members of this family are classified into two groups, including pro-apoptotic or anti-apoptotic proteins, and are in the forms of homodimers or heterodimers. The pro-apoptotic proteins are further classified as multi-domain members, such as BCL-2 homology (BH) domain proteins such as BAX, BCLXs, and BAK, or single domain members, including BH3-only proteins BID, BIM, BAD, PUMA (p53 upregulated controller of apoptosis), and NOXA. The anti-apoptotic members contain multi-BH domain and include BCL-2, BCL-XL and MCL-1. Owing to the crucial role of BCL-2 family proteins, especially BH3-only proteins, in regulating and promoting apoptosis, they could be a potential target for therapeutic options [30]. Under normal physiological conditions, there is a balance between pro-apoptotic (BAX, BID, BAK or BAD) and anti-apoptotic (BCL-XL and BCL-2) members of the BCL-2 family. This balance can be disrupted by an internal stimulus, leading to an increase in the pro-apoptotic BCL-2 family members or the decrease in the anti-apoptotic BCL-2 family proteins. In most conditions, pro-apoptotic homodimers in the outer membrane of the mitochondrion are formed to make the mitochondrial membrane permeable to release cytochrome c and SMAC which, in turn, trigger the activation of apoptosis cascade [31].
Codelivery in Nanoparticle-based siRNA for Cancer Therapy
Published in Loutfy H. Madkour, Nanoparticle-Based Drug Delivery in Cancer Treatment, 2022
Among nondrug pump–related mechanisms, the most important is the activation of antiapoptotic pathways; a defense mechanism that rescues cells from cell death [38]. Apoptosis is the most common type of programmed cell death and is an essential part of the cell cycle. Apoptosis is activated by a series of cascade signals in which many proteins are involved. Bcl-2 is a protein of the Bcl-2 family, encoded by the gene BCL-2, which has a major role in preventing apoptosis in healthy cells [11]. Bcl-2 overexpression prevents cells from entering apoptosis. It is correlated with cancer cell survival and cancer cell resistance. Other members of the Bcl-2 family, such as Mcl-1, a protein encoded by the gene MCL-1, have been identified as inhibitors of apoptosis [39].
Formulation and evaluation of a two-stage targeted liposome coated with hyaluronic acid for improving lung cancer chemotherapy and overcoming multidrug resistance
Published in Journal of Biomaterials Science, Polymer Edition, 2023
Xuelian Wang, Hongye Cai, Xinyu Huang, Zhuhang Lu, Luxi Zhang, Junjie Hu, Daizhi Tian, Jiyu Fu, Guizhi Zhang, Yan Meng, Guohua Zheng, Cong Chang
Apoptosis, a form of programmed cell death, is crucial for preventing cancer development, and inducing apoptosis has become a popular target for cancer treatment [42]. There are two major apoptotic pathways: the exogenous (mitochondrial pathway) and endogenous pathways (death receptor pathway), both of which aim to initiate cell death. The Bcl-2 protein family plays a key role in apoptosis regulation, including anti-apoptotic/pro-survival proteins such as BCL-2, BCL-XL, as well as pro-apoptotic proteins such as Bax and Bak. In the mitochondrial apoptosis pathway, activated Bax forms multimeric pores in the mitochondrial membrane, leading to a decrease in MMP and an increase in membrane permeability [43]. Subsequently, a series of apoptotic factors are released from mitochondria into the cytoplasm. The apoptosis initiator protease caspase-9 is then activated, followed by downstream effector caspase-3 activation, ultimately inducing apotosis. As shown in Figure 9E–F, after treatment with HA/TT LP/PTX, the expression of the anti-apoptotic protein Bcl-2 was downregulated, while the expression of Bax, cleaved caspase 3, and cleaved caspase 9 was upregulated, indicating the induction of apoptosis.
Inhibitory potentials of phytocompounds from Ocimum gratissimum against anti-apoptotic BCL-2 proteins associated with cancer: an integrated computational study
Published in Egyptian Journal of Basic and Applied Sciences, 2022
Gideon A. Gyebi, Oludare M. Ogunyemi, Ibrahim M. Ibrahim, Saheed O. Afolabi, Rotimi J. Ojo, Uju D.I. Ejike, Joseph O. Adebayo
The members of the anti-apoptotic B cell lymphoma 2 (BCL- 2) protein family play key regulatory roles in cellular apoptosis. Deregulation of the normal apoptotic process in the cell, driven by the members of the BCL-2 proteins, is a fundamental element in carcinogenesis [1]. The Bcl-2 proteins are reportedly overexpressed in about half of all human cancers which reveals the involvement of the anti-apoptotic members in carcinogenesis (Yip and Reed 2008). The four BH (BH1, BH2, BH3 and BH4) conserved domains, which were identified from nuclear magnetic resonance (NMR) investigation in 2001 [2], are critical for the signaling functions of these proteins. The BH1-BH3 domain forms a hydrophobic groove, while the BH4 stabilizes the entire structure. The BH3 domain which resides superficially on the anti-apoptotic proteins plays a central role as it accommodates pro-apoptotic partners (Bax/Bak) [3]. On account of this structural built up, substances that interact with the critical amino acid residues in this groove serve as promising inhibitors that may interfere with anti-apoptotic BCL-2 proteins; and thereby promote apoptosis in cancer cells [4]. In this direction, navitoclax [5] and ABT-199 [6] and other drugable compounds have been developed through combinatorial technique and are under way through clinical trials for treatment of cancers [7]. Thus, targeting the BCL- 2 proteins, which are known to perform pivotal functions in the regulation of apoptosis, have been explored toward developing anticancer drugs.
Neurotoxicity of β-HgS differs from environmental mercury pollutants (MeHgCl and HgCl2) in Neuro-2a cell
Published in International Journal of Environmental Health Research, 2021
Zhenghua Xia, Hongtao Bi, Cen Li, Lujing Geng, Muhammad Usman, Yuzhi Du, Lixin Wei
Bcl-2 family proteins are involved in the response to apoptosis (Ji et al. 2008). Due to Bcl-2 family proteins has been proved to regulate mitochondrial-dependent apoptosis meanwhile balance anti- and pro-apoptotic members to arbitrate life/death decisions, therefore the ratio of Bcl-2 to Bax can use as a pivotal factor to determines whether apoptosis will occur in the cells exposed to injurious chemicals (Cheng et al. 2007; Pradelli et al. 2010). With the increase of incubation time, compared with the control group, the ratios of Bcl-2 and Bak in MeHg group decreased gradually, while the ratio of β-HgS increased gradually. Furthermore, our previous study found that mercury could affect the release of inflammatory cytokines in neuroglial cells (Tan et al. 2018). In this study, compare with the control group, the expressions of TNF-α, IL-6 and IL-1β in MeHgCl group were up-regulated significantly in 6 h, 12 h and 24 h, and the expressions of IL-1β and IL-6 in HgCl2 group was increased significant in 6 h and 24 h respectively. While, there was only significantly up-regulated of IL-6 in Neuro-2a cells after β-HgS exposure for 24 h. These findings indicate that β-HgS is much less neurotoxicity than MeHgCl and HgCl2 in Neuro-2a cells. However, the critical roles of these differences were still required investigation in the future.