Vitamin�C induces human melanoma A375 cell apoptosis via Bax‑ and Bcl‑2‑mediated mitochondrial pathways

Chen, Xiaoyu; Chen, Ying; Qu, Chuanjun; Pan, Zhaohai; Yao, Qing; Zhang, Xin; Liu, Wenjing; Li, De‐Fang; Zheng, Qiusheng

doi:10.3892/ol.2019.10686

Cited by 16 publications

(14 citation statements)

References 39 publications

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“…30 Studies have shown that Bcl2 gene damage is related to the occurrence and development of various cancers such as lung cancer, breast cancer and colorectal cancer. [31][32][33] Caspase9 protein is a member of the cysteine-aspartic protease (caspase) family and can be activated by interacting with caspase-3. Caspase9 can be activated in the mitochondrial apoptotic pathway and becomes its active form cleaved-caspase9, which plays an important role in the execution of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

<p>Omega-3PUFA Attenuates MNU-Induced Colorectal Cancer in Rats by Blocking PI3K/AKT/Bcl-2 Signaling</p>

Huang

Chun-an

Cai

et al. 2020

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Background: Omega 3 polyunsaturated fatty acid (Omega-3PUFA) is one of the essential nutrients for human body involved in intracellular metabolic regulation and cell signaling. Previous studies have shown that Omega-3PUFA is involved in the pathogenesis of digestive system tumors, including colorectal cancer (CRC), however, the effects of Omega-3PUFA on CRC has not been fully elucidated. In the current study, we evaluated whether Omega-3PUFA can alleviate N-methyl-N-nitrosourea(MNU) induced CRC in a rat model and illustrated the potential mechanism. Methods: The effects of Omga-3PUFA on MNU-induced colorectal cancer in rats were analyzed by in vivo experiments. The viability, apoptosis, colony formation and invasion of CRC cells treated with Omga-3PUFA were detected by CCK8, flow cytometry, clone formation assay and transwell invasion assay. The expression of apoptosis-related proteins in CRC cells treated with Omga-3PUFA was detected by Western blotting. Finally, after adding PI3K activator, the viability, apoptosis and protein expression of CRC cells treated with Omga-3PUFA were detected by CCK8, flow cytometry and Western blotting. Results: Our results showed that Omega-3PUFA attenuated MNU-induced CRC in rats and inhibited AKT/Bcl-2 signaling in rats. In addition, Omega-3PUFA inhibited CRC cell proliferation and induces CRC cell apoptosis. Moreover, Omega-3PUFA inhibited CRC cell colony formation and invasion, and inhibited PI3K/AKT/Bcl-2 signaling in CRC cells. Furthermore, The effects of Omega-3PUFA on cell proliferation and apoptosis were inhibited by blocking PI3K/AKT signaling. Conclusion: Omega-3PUFA can attenuate MNU-induced colorectal cancer in rats by blocking PI3K/AKT/Bcl-2 signaling, which suggests that Omega-3PUFA may be a potent agent for CRC treatment.

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Section: Discussionmentioning

confidence: 99%

<p>Omega-3PUFA Attenuates MNU-Induced Colorectal Cancer in Rats by Blocking PI3K/AKT/Bcl-2 Signaling</p>

Huang

Chun-an

Cai

et al. 2020

OTT

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“…Therefore, it was surprising to observe that formulation 1 diluted at 100%, 50%, or 10% decreased the viability of human skin ex vivo, whereas formulation 2 or ascorbic acid at 8% did not. However, it has been reported that the administration of vitamin C less than 4 mmol/L is an antioxidant that inactivates ROS and promote the cell proliferation while doses up to 20 mmol/L of vitamin C stimulates the production of the ROS and induces cell apoptosis 33‐36 . High doses of vitamin C (from 1.5 mmol/L) reduces the cell survival through the production of ROS and the activation of cell apoptosis cascade via caspase‐3 activation in breast, melanoma, and gastric cancer cell and cancer stem cell cultures 33‐36 .…”

Section: Discussionmentioning

confidence: 99%

“…However, it has been reported that the administration of vitamin C less than 4 mmol/L is an antioxidant that inactivates ROS and promote the cell proliferation while doses up to 20 mmol/L of vitamin C stimulates the production of the ROS and induces cell apoptosis 33‐36 . High doses of vitamin C (from 1.5 mmol/L) reduces the cell survival through the production of ROS and the activation of cell apoptosis cascade via caspase‐3 activation in breast, melanoma, and gastric cancer cell and cancer stem cell cultures 33‐36 . The formulation 1 at 50% and 10% used in this study has about 500 mmol/L and 100 mmol/L of vitamin C. Thus, high dose of vitamin C (up to 1.5 mmol/L) observed in the formulation 1 could be involved in the reduction of tissue viability probably through the generation of ROS and promotion of cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Topical application of a commercially available formulation of vitamin C stabilized by vitamin E and ferulic acid reduces tissue viability and protein synthesis in ex vivo human normal skin

Romana‐Souza

Silva-Xavier

Monte‐Alto‐Costa

2020

J of Cosmetic Dermatology

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Background Aqueous formulations of vitamin C stabilized by vitamin E and ferulic acid at low pH effectively protect skin against reactive oxygen species‐induced damage. However, the effects of these formulations on human skin have not clearly been described. The aim of this study was to investigate whether topical application of two commercially available formulations of vitamin C alter human skin using an ex vivo model. Methods Human skin explants were topically treated on alternate days with commercially available formulation 1 (15% vitamin C) at 100% (without dilution), 50%, or 10% diluted in saline or formulation 2 (20% vitamin C) at 100% (without dilution), 50%, or 10% diluted in saline. Only saline was applied to control skin explants. Results Topical formulation 1 at 100%, 50%, or 10%, but not formulation 2 at 100%, 50%, or 10%, reduced the viability of ex vivo human skin compared to the control after 7, 10, and 13 days. In addition, compared to the control, ex vivo human skin treated with formulation 1 at 50%, but not formulation 2 at 50%, also decreased mRNA levels of actin and ribosomal protein L10 and gene expression of extracellular matrix components after 10 days. Furthermore, after 10 days, topical application of formulation 1 at 50%, but not formulation 2 at 50%, decreased the protein expression of proliferating cellular nuclear antigen, lysyl oxidase, β‐actin, and glyceraldehyde‐3‐phosphate dehydrogenase compared to the control. Conclusions Topical formulation 1, but not formulation 2, may reduce the viability of and protein synthesis in ex vivo human skin. Those effects might be due to action of vehicle of formulation 1 on ex vivo human skin.

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“…In vitro studies and murine models indicated that vitamin C inhibits invasion and growth in melanoma cells [ 70 , 71 , 92 ]. According to Chen et al, ascorbic acid promotes the apoptosis of melanoma cells by stimulating the Bax/Bcl-2 pathway, which leads to the activation of caspases followed by protein degradation and cell death [ 119 ]. Moreover, a recent study by Yang et al suggested that ascorbic acid induces cytotoxicity in melanoma cells in a dose-dependent manner [ 120 ].…”

Section: Vitamin C In Adjuvant Cancer Therapymentioning

confidence: 99%

Vitamin C Transporters and Their Implications in Carcinogenesis

2020

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Vitamin C is implicated in various bodily functions due to its unique properties in redox homeostasis. Moreover, vitamin C also plays a great role in restoring the activity of 2-oxoglutarate and Fe2+ dependent dioxygenases (2-OGDD), which are involved in active DNA demethylation (TET proteins), the demethylation of histones, and hypoxia processes. Therefore, vitamin C may be engaged in the regulation of gene expression or in a hypoxic state. Hence, vitamin C has acquired great interest for its plausible effects on cancer treatment. Since its conceptualization, the role of vitamin C in cancer therapy has been a controversial and disputed issue. Vitamin C is transferred to the cells with sodium dependent transporters (SVCTs) and glucose transporters (GLUT). However, it is unknown whether the impaired function of these transporters may lead to carcinogenesis and tumor progression. Notably, previous studies have identified SVCTs’ polymorphisms or their altered expression in some types of cancer. This review discusses the potential effects of vitamin C and the impaired SVCT function in cancers. The variations in vitamin C transporter genes may regulate the active transport of vitamin C, and therefore have an impact on cancer risk, but further studies are needed to thoroughly elucidate their involvement in cancer biology.

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Vitamin�C induces human melanoma A375 cell apoptosis via Bax‑ and Bcl‑2‑mediated mitochondrial pathways

Cited by 16 publications

References 39 publications

<p>Omega-3PUFA Attenuates MNU-Induced Colorectal Cancer in Rats by Blocking PI3K/AKT/Bcl-2 Signaling</p>

<p>Omega-3PUFA Attenuates MNU-Induced Colorectal Cancer in Rats by Blocking PI3K/AKT/Bcl-2 Signaling</p>

Topical application of a commercially available formulation of vitamin C stabilized by vitamin E and ferulic acid reduces tissue viability and protein synthesis in ex vivo human normal skin

Vitamin C Transporters and Their Implications in Carcinogenesis

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