Apoptosis in cancer: From pathogenesis to treatment

Division of Human Biology, School of Medical and Health Sciences, International Medical University, No. 126, Jalan Jalil Perkasa 19, Bukit Jalil 57000 Kuala Lumpur, Malaysia.
Journal of Experimental & Clinical Cancer Research (Impact Factor: 4.43). 09/2011; 30(1):87. DOI: 10.1186/1756-9966-30-87
Source: PubMed


Apoptosis is an ordered and orchestrated cellular process that occurs in physiological and pathological conditions. It is also one of the most studied topics among cell biologists. An understanding of the underlying mechanism of apoptosis is important as it plays a pivotal role in the pathogenesis of many diseases. In some, the problem is due to too much apoptosis, such as in the case of degenerative diseases while in others, too little apoptosis is the culprit. Cancer is one of the scenarios where too little apoptosis occurs, resulting in malignant cells that will not die. The mechanism of apoptosis is complex and involves many pathways. Defects can occur at any point along these pathways, leading to malignant transformation of the affected cells, tumour metastasis and resistance to anticancer drugs. Despite being the cause of problem, apoptosis plays an important role in the treatment of cancer as it is a popular target of many treatment strategies. The abundance of literature suggests that targeting apoptosis in cancer is feasible. However, many troubling questions arise with the use of new drugs or treatment strategies that are designed to enhance apoptosis and critical tests must be passed before they can be used safely in human subjects.

Download full-text


Available from: Rebecca Shin Yee Wong, May 27, 2014
  • Source
    • "Biochemical changes in apoptosis, DNA fragmentation and caspase activation, may explain in part some of the morphological changes in apoptosis. Therefore, it is important to note that apoptosis may occur without oligonucleosomal DNA fragmentation and can be caspase-independent [31] "
    [Show abstract] [Hide abstract]
    ABSTRACT: A new synthesis of goniobutenolides A (1) and B (2) and the corresponding 7-epimers has been achieved starting from diacetone d-glucose. The key step of the synthesis is a new one-pot sequence that commenced with Z-selective Wittig (or Horner-Wadsworth-Emmons) olefination, followed by successive γ-lactonisation and β-elimination. The above-mentioned unsaturated lactones were then converted to the corresponding 5-halogenated crassalactone D derivatives by using the appropriate haloetherification protocol. The most of synthesized compounds exhibited potent cytotoxic activities against a panel of tumour cell lines. The main structural features responsible for their antitumour potency have been revealed by means of SAR analysis. Flow cytometry data suggested that cytotoxic effects of these compounds in the culture of K562 cells might be mediated by apoptosis, additionally revealing that these molecules induced changes in cell cycle distribution of these cells. Results of semi-quantitative Western blot analysis indicate that the most of synthesized compounds induce apoptosis in a caspase-dependent manner.
    Full-text · Article · Jan 2016 · European Journal of Medicinal Chemistry
  • Source
    • "For example, BRCA2 participates in homologous recombination and regulating the S-phase checkpoint, and mutations of deficiencies in BRCA2 are strongly associated with tumorigenesis [53].Table 3 The common pathways by using DAVID and CPDB for early-stage NSCLC (the p M -value and p T -value represent the corresponding p-value obtained by machine learning algorithms and topological parameter-based classification)Table 4 agrees closely with the results of our previous work [6], which also identified cell-cycle, the mitotic anaphase, DNA replication, the sister-chromatid segregation process, the Cdc20:Phospho-APC/C-mediated degradation of Cy-clin A, the M-phase and mitotic G1- G1/S phases. Although defective apoptosis is critical to the development and progression of cancer, apoptosis is important in the treatment of cancer as it is a popular target of many treatment strategies [54]. Wong et al. [55] noted that PKG-Iα kinase activity is necessary to maintaining high levels of cAMP response element binding (CREB) phosphorylation at ser133, and promotes the formation of colonies in NSCLC cells. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Non-small cell lung cancer (NSCLC) is one of the leading causes of death globally, and research into NSCLC has been accumulating steadily over several years. Drug repositioning is the current trend in the pharmaceutical industry for identifying potential new uses for existing drugs and accelerating the development process of drugs, as well as reducing side effects. This work integrates two approaches - machine learning algorithms and topological parameter-based classification - to develop a novel pipeline of drug repositioning to analyze four lung cancer microarray datasets, enriched biological processes, potential therapeutic drugs and targeted genes for NSCLC treatments. A total of 7 (8) and 11 (12) promising drugs (targeted genes) were discovered for treating early- and late-stage NSCLC, respectively. The effectiveness of these drugs is supported by the literature, experimentally determined in-vitro IC 50 and clinical trials. This work provides better drug prediction accuracy than competitive research according to IC 50 measurements. With the novel pipeline of drug repositioning, the discovery of enriched pathways and potential drugs related to NSCLC can provide insight into the key regulators of tumorigenesis and the treatment of NSCLC. Based on the verified effectiveness of the targeted drugs predicted by this pipeline, we suggest that our drug-finding pipeline is effective for repositioning drugs.
    Full-text · Article · Jan 2016 · BMC Bioinformatics
  • Source
    • "One of the hallmarks of cancer is resistance to programmed cell death or apoptosis [19]. Biochemical and morphological measures can be used to characterize apoptosis, such as pyknosis, chromatin condensation, and formation of apoptotic bodies [20], cell shrinkage [21], DNA fragmentation [22] and structure disruption of membrane [23] . "
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To investigate the cytotoxic activity of the hexane and ethyl acetate extracts of Curcuma mangga rhizomes against human colorectal adenocarcinoma cell lines (HT29). Methods: The cytotoxic activity of the hexane and ethyl acetate extracts of Curcuma mangga rhizomes against human colorectal adenocarcinoma cell lines (HT29) was determined by using the SRB assay. Results: The ethyl acetate extract showed a higher cytotoxic effect compared to the hexane extract. Morphological changes of the HT29 cells such as cell shrinkage, membrane blebbling and formation of apoptotic bodies while changes in nuclear morphology like chromatin condensation and nuclear fragmentation were observed. Further evidence of apoptosis in HT29 cells was further supported by the externalization of phosphatidylserine which indicate early sign of apoptosis. Conclusions: The early sign of apoptosis is consistent with the cell cycle arrest at the G0/G1 checkpoint which suggests that the changes on the cell cycle lead to the induction of apoptosis in HT29.
    Full-text · Article · Dec 2015 · Asian Pacific Journal of Tropical Medicine
Show more