Role of Bcl-2 Family Proteins in Photodynamic Therapy Mediated Cell Survival and Regulation

Aniogo, Eric Chekwube; George, Blassan P.; Abrahamse, Heidi

doi:10.3390/molecules25225308

Cited by 32 publications

(11 citation statements)

References 96 publications

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“…Among the members of this family, there are pro-apoptotic proteins (e.g., Bid, Bax) and proteins that inhibit this process (e.g., Bcl-2). Thanks to these two opposite types of regulatory proteins, it is possible to maintain the homeostasis of the processes of this type of programmed cell death [38,39].…”

Section: Discussionmentioning

confidence: 99%

Effect of Resveratrol Treatment on Human Pancreatic Cancer Cells through Alterations of Bcl-2 Family Members

et al. 2021

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Pancreatic cancers are among of the most lethal types of neoplasms, and are mostly detected at an advanced stage. Conventional treatment methods such as chemotherapy or radiotherapy often do not bring the desired therapeutic effects. For this reason, natural compounds are increasingly being used as adjuvants in cancer therapy. Polyphenolic compounds, including resveratrol, are of particular interest. The aim of this study is to analyze the antiproliferative and pro-apoptotic mechanisms of resveratrol on human pancreatic cells. The study was carried out on three human pancreatic cancer cell lines: EPP85-181P, EPP85-181RNOV (mitoxantrone-resistant cells) and AsPC-1, as well as the normal pancreatic cell line H6c7. The cytotoxicity of resveratrol in the tested cell lines was assessed by the colorimetric method (MTT) and the flow cytometry method. Three selected concentrations of the compound (25, 50 and 100 µM) were tested in the experiments during a 48-h incubation. TUNEL and Comet assays, flow cytometry, immunocytochemistry, confocal microscopy, real-time PCR and Western Blot analyses were used to evaluate the pleiotropic effect of resveratrol. The results indicate that resveratrol is likely to be anticarcinogenic by inhibiting human pancreatic cancer cell proliferation. In addition, it affects the levels of Bcl-2 pro- and anti-apoptotic proteins. However, it should be emphasized that the activity of resveratrol was specific for each of the tested cell lines, and the most statistically significant changes were observed in the mitoxantrone-resistant cells.

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Section: Discussionmentioning

confidence: 99%

Effect of Resveratrol Treatment on Human Pancreatic Cancer Cells through Alterations of Bcl-2 Family Members

et al. 2021

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“…Apoptosis is a highly regulated cell death mechanism. It involves the initiation of numerous pathways following the damages of several organelles [16]. Mitochondria play a key role in apoptosis regulation and any PS localized on the organelle triggered the process.…”

Section: Biochemical Effects Of Pdt and Reactive Oxygen Species (Ros)...mentioning

confidence: 99%

“…Mitochondria play a key role in apoptosis regulation and any PS localized on the organelle triggered the process. Leakage of the cytochrome c from the mitochondria into the cytosol can activate caspase proteins to induce signal transduction that leads to apoptosis [16,17]. Cell death by necrosis is extensive damage of cell components at PS site of action that results in leakage of intracellular material that can cause inflammation.…”

Section: Biochemical Effects Of Pdt and Reactive Oxygen Species (Ros)...mentioning

confidence: 99%

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Molecular Effectors of Photodynamic Therapy-Mediated Resistance to Cancer Cells

Aniogo

George

Abrahamse

2021

IJMS

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Photodynamic therapy (PDT) is currently enjoying considerable attention as the subject of experimental research to treat resistant cancers. The preferential accumulation of a non-toxic photosensitizer (PS) in different cellular organelles that causes oxidative damage by combining light and molecular oxygen leads to selective cell killing. However, one major setback, common among other treatment approaches, is tumor relapse and the development of resistance causing treatment failure. PDT-mediated resistance could result from increased drug efflux and decreased localization of PS, reduced light exposure, increased DNA damage repair, and altered expression of survival genes. This review highlights the essential insights of PDT reports in which PDT resistance was observed and which identified some of the molecular effectors that facilitate the development of PDT resistance. We also discuss different perceptions of PDT and how its current limitations can be overturned to design improved cancer resistant treatments.

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“…These results suggested that ATO could promote the apoptosis-inducing effect of Met on HeLa cells. Bcl-2 family proteins are key molecules in the regulation of apoptosis, and can act directly or indirectly on mitochondria to perform their corresponding functions [30]. Compared with treatment of HeLa cells with Met or ATO alone, the combination of 40 mmol/L Met and 4 µmol/L ATO resulted in significant downregulation of the anti-apoptotic protein Bcl-2, significant upregulation of the pro-apoptotic protein Bax, and an increased Bax/Bcl-2 ratio (Figure 2B).…”

Section: Changes In Cell Morphologymentioning

confidence: 99%

Metformin and arsenic trioxide synergize to trigger Parkin/pink1-dependent mitophagic cell death in human cervical cancer HeLa cells

Chen¹,

Zhou²,

Yi³

et al. 2021

J. Cancer

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Mitochondria are involved in various biological processes including intracellular homeostasis, proliferation, senescence, and death, and mitochondrial mitophagy is closely related to the development and regression of malignant tumors. Recent studies confirmed that the hypoglycemic drug metformin (Met) exerted various antitumor effects, protected neural cells, and improved immunity, while arsenic trioxide (ATO) is an effective chemotherapeutic agent for the clinical treatment of leukemia and various solid tumors. However, the possible combined antitumor effects of Met and ATO and their cellular molecular mechanisms are unclear. We investigated the role of Parkin-mediated mitochondrial mitophagy in the anti-tumor mechanism of Met and ATO by studying the effects of Met and/or ATO on the proliferation and apoptosis of cervical cancer HeLa cells. Both Met and ATO effectively inhibited the proliferative activity of HeLa cells and induced apoptosis by activating Bax and inhibiting Bcl-2. Met and ATO treatment alone or in combination stimulated mitophagosome accumulation in HeLa cells, increased the conversion of microtubule-associated protein light chain 3 (LC3)-I to LC3-II, and decreased levels of the mitophagic lysosomal substrate protein P62. The mitochondrial membrane potential of HeLa cells also decreased, accompanied by activation of the mitochondrial translocase TOM system and the Pink1/Parkin signaling pathway. These results suggested that Met and/or ATO could induce mitophagy in HeLa cells via the Pink1/Parkin signaling pathway, leading to mitophagic apoptosis and inhibition of tumor cell proliferation. The combination of Met and ATO thus has enhanced antitumor effects, suggesting that this combination has potential clinical applications for the treatment of cervical cancer and other tumors.

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Role of Bcl-2 Family Proteins in Photodynamic Therapy Mediated Cell Survival and Regulation

Cited by 32 publications

References 96 publications

Effect of Resveratrol Treatment on Human Pancreatic Cancer Cells through Alterations of Bcl-2 Family Members

Effect of Resveratrol Treatment on Human Pancreatic Cancer Cells through Alterations of Bcl-2 Family Members

Molecular Effectors of Photodynamic Therapy-Mediated Resistance to Cancer Cells

Metformin and arsenic trioxide synergize to trigger Parkin/pink1-dependent mitophagic cell death in human cervical cancer HeLa cells

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