BH3-Only Proteins Noxa and Puma Are Key Regulators of Induced Apoptosis

Roufayel, Rabih; Younes, Khaled; Al-Sabi, Ahmed; Murshid, Nimer

doi:10.3390/life12020256

Cited by 46 publications

(34 citation statements)

References 187 publications

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“…In response to DNA and oxidative stress, p53 accumulates into the cytoplasmic matrix, where it interacts with pro-apoptotic proteins, such as Bax and Bak, BH3-only pro-apoptotic protein initiators, and other members Bcl-2 family of proteins. These molecular interactions may directly or indirectly promote MOMP and tumor cell death by apoptosis [ 69 , 70 ].…”

Section: Discussionmentioning

confidence: 99%

In Vitro Cell Death Mechanisms Induced by Dicoma anomala Root Extract in Combination with ZnPcS4 Mediated-Photodynamic Therapy in A549 Lung Cancer Cells

Chota

George

Abrahamse

2022

Cells

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Globally, lung cancer has remained the leading cause of morbidity and mortality in men and women. To enhance photodynamic therapeutic effects in vitro, the present study was designed to reduce dose-dependence in photodynamic therapy (PDT) and evaluate the anticancer effects of Dicoma anomala (D. anomala) root extracts (i.e., chloroform (Chl), ethyl acetate (EtOAc), and methanol (MeOH)) on A549 lung cancer cells. The most active extract of D. anomala (D.A) was used to establish the 50% inhibitory concentration (IC50), which was further used to evaluate the anticancer efficacy of D.A in combination with ZnPcS4-mediated PDT IC50. The study further evaluated cell death mechanisms by cell viability/ cytotoxicity (LIVE/DEADTM assay), flow cytometry (Annexin V-fluorescein isothiocyanate (FITC)-propidium iodide (PI) staining), immunofluorescence (p38, p53, Bax, and caspase 3 expressions), and fluorometric multiplex assay (caspase 8 and 9) 24 h post-treatment with IC50 concentrations of ZnPcS4-mediated PDT and D.A MeOH root extract. Morphological changes were accompanied by a dose-dependent increase in cytotoxicity, decrease in viability, and proliferation in all experimental models. Apoptosis is the highly favored cell death mechanism observed in combination therapy groups. Apoptotic activities were supported by an increase in the number of dead cells in the LIVE/DEADTM assay, and the upregulation of p38, p53, Bax, caspase 3, 8, and 9 apoptotic proteins. In vitro experiments confirmed the cytotoxic and antiproliferative effects of D.A root extracts in monotherapy and in combination with ZnPcS4-mediated PDT. Taken together, our findings demonstrated that D.A could be a promising therapeutic candidate worth exploring in different types of cancer.

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Section: Discussionmentioning

confidence: 99%

In Vitro Cell Death Mechanisms Induced by Dicoma anomala Root Extract in Combination with ZnPcS4 Mediated-Photodynamic Therapy in A549 Lung Cancer Cells

Chota

George

Abrahamse

2022

Cells

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“…BOK is not as stable as BAX and BAK, and its cellular level is regulated by the endoplasmic reticulum-associated degradation (ERAD) pathway ( 68 ). Human BOK is the only protein with a leucine sequence in BCL-2, and high expression of BOK accelerates morphological changes in mitochondria ( 69 ), ER ( 70 ), and Golgi bodies ( 67 ). This finding suggests that BOK may play an important role in shaping organelle membranes and suggests the presence of nuclear output signals in the BH3 domain.…”

Section: The Structural Domains Of Bcl-2 Family Proteinsmentioning

confidence: 99%

The role of BCL-2 family proteins in regulating apoptosis and cancer therapy

et al. 2022

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Apoptosis, as a very important biological process, is a response to developmental cues or cellular stress. Impaired apoptosis plays a central role in the development of cancer and also reduces the efficacy of traditional cytotoxic therapies. Members of the B-cell lymphoma 2 (BCL-2) protein family have pro- or anti-apoptotic activities and have been studied intensively over the past decade for their importance in regulating apoptosis, tumorigenesis, and cellular responses to anticancer therapy. Since the inflammatory response induced by apoptosis-induced cell death is very small, at present, the development of anticancer drugs targeting apoptosis has attracted more and more attention. Consequently, the focus of this review is to summarize the current research on the role of BCL-2 family proteins in regulating apoptosis and the development of drugs targeting BCL-2 anti-apoptotic proteins. Additionally, the mechanism of BCL-2 family proteins in regulating apoptosis was also explored. All the findings indicate the potential of BCL-2 family proteins in the therapy of cancer.

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“…On the other hand, NOXA and other BH3-only family proteins can promote autophagic cell death by deregulating the Bcl-2 family members that bind Beclin-1 [ 117 ]. In addition, Beclin-1 may also be the target of several endoproteases that hydrolyze peptide such as caspase-3 and caspase-8.…”

Section: Autophagy and Apoptosismentioning

confidence: 99%

Molecular Mechanisms of Autophagy in Cancer Development, Progression, and Therapy

et al. 2022

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Autophagy is an evolutionarily conserved and tightly regulated process that plays an important role in maintaining cellular homeostasis. It involves regulation of various genes that function to degrade unnecessary or dysfunctional cellular components, and to recycle metabolic substrates. Autophagy is modulated by many factors, such as nutritional status, energy level, hypoxic conditions, endoplasmic reticulum stress, hormonal stimulation and drugs, and these factors can regulate autophagy both upstream and downstream of the pathway. In cancer, autophagy acts as a double-edged sword depending on the tissue type and stage of tumorigenesis. On the one hand, autophagy promotes tumor progression in advanced stages by stimulating tumor growth. On the other hand, autophagy inhibits tumor development in the early stages by enhancing its tumor suppressor activity. Moreover, autophagy drives resistance to anticancer therapy, even though in some tumor types, its activation induces lethal effects on cancer cells. In this review, we summarize the biological mechanisms of autophagy and its dual role in cancer. In addition, we report the current understanding of autophagy in some cancer types with markedly high incidence and/or lethality, and the existing therapeutic strategies targeting autophagy for the treatment of cancer.

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BH3-Only Proteins Noxa and Puma Are Key Regulators of Induced Apoptosis

Cited by 46 publications

References 187 publications

In Vitro Cell Death Mechanisms Induced by Dicoma anomala Root Extract in Combination with ZnPcS4 Mediated-Photodynamic Therapy in A549 Lung Cancer Cells

In Vitro Cell Death Mechanisms Induced by Dicoma anomala Root Extract in Combination with ZnPcS4 Mediated-Photodynamic Therapy in A549 Lung Cancer Cells

The role of BCL-2 family proteins in regulating apoptosis and cancer therapy

Molecular Mechanisms of Autophagy in Cancer Development, Progression, and Therapy

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