Combination of withaferin A and X-ray irradiation enhances apoptosis in U937 cells

Yang, Eun Sun; Choi, Min Jung; Kim, Jin Hee; Choi, Kyeong Sook; Kwon, Taeg Kyu

doi:10.1016/j.tiv.2011.09.016

Cited by 42 publications

(17 citation statements)

References 31 publications

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“…Mitochondria play an important role in apoptotic pathways that result from a variety of intracellular events including the release of caspase activators, changes in MMP, ROS generation, and changes in the Bcl-2 family of proteins (22). In the current study, loss of MMP was observed in A549 cells co-treated with MB and PDT (Fig.…”

Section: Discussionsupporting

confidence: 56%

Methylene blue-mediated photodynamic therapy enhances apoptosis in lung cancer cells

et al. 2013

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Combined treatment with a photosensitizer and iodide laser [photodynamic therapy (PDT)] has improved the outcome of various cancers. In this study, we investigated the effects of using the photosensitizer methylene blue (MB) in PDT in human lung adenocarcinoma cells. We found that MB enhances PDT-induced apoptosis in association with downregulation of anti-apoptotic proteins, reduced mitochondrial membrane potential (MMP), increased phosphorylation of the mitogen-activated protein kinase (MAPK) and the generation of reactive oxygen species (ROS). In MB-PDT-treated A549 cells, we observed PARP cleavage, procaspase-3 activation, downregulation of the anti-apoptotic proteins Bcl-2 and Mcl-1, and the reduction of mitochondrial membrane potential (MMP). Western blot data showed that phosphorylation of p38 was increased in MB-PDT-treated A549 cells, indicating that several signaling molecules participate in the apoptotic cascade. Our data also showed that apoptotic cell death in MB-PDT-treated cells occurred through a series of steps beginning with the photochemical generation of ROS. Demonstrating the role of ROS, pretreatment of A549 cells with the antioxidant N-acetylcysteine (NAC) followed by MB-PDT resulted in increased cell viability and reduced proteolytic cleavage of PARP.

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Section: Discussionsupporting

confidence: 56%

Methylene blue-mediated photodynamic therapy enhances apoptosis in lung cancer cells

et al. 2013

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“…Several studies have shown sensitization of cultured cancer cells to chemotherapy drugs and radiation in the presence of WA (49,60,(92)(93)(94). For example, WA and sorafenib exhibited synergistic efficacy in thyroid cancer cells (49).…”

Section: Combination Chemotherapies With Wamentioning

confidence: 99%

Molecular Targets and Mechanisms of Cancer Prevention and Treatment by Withaferin A, A Naturally Occurring Steroidal Lactone

Vyas

Singh

2013

AAPS J

105

108

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The plants used in Ayurvedic medicine, which has been practiced in India for thousands of years for the treatment of a variety of disorders, are rich in chemicals potentially useful for prevention and treatment of cancer. Withania somnifera (commonly known as Ashwagandha in Ayurvedic medicine) is one such medicinal plant whose anticancer value was realized over four decades ago after isolation of a crystalline steroidal compound (withaferin A) from the leaves of this shrub. The root and leaf extracts of W. somnifera are shown to confer protection against chemically-induced cancers in experimental rodents, and retard tumor xenograft growth in athymic mice. Anticancer effect of W. somnifera is generally attributable to steroidal lactones collectively referred to as withanolides. Withaferin A (WA) appears most active against cancer among structurally divergent withanolides isolated from the root or leaf of W. somnifera. Cancer-protective role for WA has now been established using chemically-induced and oncogene-driven rodent cancer models. This review summarizes the key in vivo preclinical studies demonstrating anticancer effects of WA. Molecular targets and mechanisms likely contributing to the anticancer effects of WA are also discussed. Finally, challenges in clinical development of WA for the prevention and treatment of cancer are highlighted.

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“…Therefore, it may be extrapolated that anti-cancer compounds capable of inflicting additional oxidative stress may cause cell death. Indeed, there is emerging evidence that increased generation of ROS achievable by chemotherapy and/or radiotherapy can induce apoptosis in cancer cells [5], [6].…”

Section: Introductionmentioning

confidence: 99%

Malabaricone-A Induces A Redox Imbalance That Mediates Apoptosis in U937 Cell Line

et al. 2012

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BackgroundThe ‘two-faced’ character of reactive oxygen species (ROS) plays an important role in cancer biology by acting both as secondary messengers in intracellular signaling cascades and sustaining the oncogenic phenotype of cancer cells, while on the other hand, it triggers an oxidative assault that causes a redox imbalance translating into an apoptotic cell death.Principal FindingsUsing a tetrazolium [{3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl}-2H-tetrazolium] based cell viability assay, we evaluated the cytotoxicity of a plant derived diarylnonanoid, malabaricone-A on leukemic cell lines U937 and MOLT-3. This cytotoxicity hinged on its ability to cause a redox imbalance via its ability to increase ROS, measured by flow cytometry using 5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate and by decreasing glutathione peroxidase activity. This redox imbalance mediated apoptosis was evident by an increase in cytosolic [Ca2+], externalization of phosphatidyl serine as also depolarization of the mitochondrial membrane potential as measured by flow cytometry. There was concomitant peroxidation of cardiolipin, release of free cytochrome c to cytosol along with activation of caspases 9, 8 and 3. This led to cleavage of the DNA repair enzyme, poly (ADP-ribose) polymerase that caused DNA damage as proved by labeling with 4′,6-diamidino-2-phenylindole (DAPI); furthermore, terminal deoxy ribonucleotide transferase catalysed incorporation of deoxy uridine triphosphate confirmed DNA nicking and was accompanied by arrest of cell cycle progression.ConclusionsTaken together, compounds like MAL-A having pro-oxidant activity mediate their cytotoxicity in leukemic cells via induction of oxidative stress triggering a caspase dependent apoptosis.

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Combination of withaferin A and X-ray irradiation enhances apoptosis in U937 cells

Cited by 42 publications

References 31 publications

Methylene blue-mediated photodynamic therapy enhances apoptosis in lung cancer cells

Methylene blue-mediated photodynamic therapy enhances apoptosis in lung cancer cells

Molecular Targets and Mechanisms of Cancer Prevention and Treatment by Withaferin A, A Naturally Occurring Steroidal Lactone

Malabaricone-A Induces A Redox Imbalance That Mediates Apoptosis in U937 Cell Line

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