Correction: Metformin Induces Cell Cycle Arrest, Reduced Proliferation, Wound Healing Impairment In Vivo and Is Associated to Clinical Outcomes in Diabetic Foot Ulcer Patients

Ochoa-Gonzalez, Fatima; Cervantes-Villagrana, Alberto R.; Fernández-Ruiz, Julio César; Nava-Ramirez, Hilda S.; Hernandez-Correa, Adriana C.; Enciso-Moreno, José Antonio; Castañeda-Delgado, Julio Enrique

doi:10.1371/journal.pone.0159468

Cited by 5 publications

(7 citation statements)

References 1 publication

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“…Their study also revealed that metformin use could enlarge ulcer size in patients with deep foot ulcers but with a significantly lower risk of amputation. 29 Charcot foot is a serious diabetic foot lesion that is not easy to diagnose early. The deformity of Charcot foot may be treated by the use of minimally invasive surgery for tibiotalocalcaneal arthrodesis with intramedullary nail to prevent future foot ulcers, infections or even amputations.…”

Section: Discussionmentioning

confidence: 99%

Metformin and the risks of cellulitis, foot infections, and amputation in patients with type 2 diabetes

Yeh,

Yen,

Wei

et al. 2024

Journal of the Chinese Medical Association

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Background: Patients with diabetes tend to have cellulitis, foot infections, and amputation. We conducted this research to compare the risks of cellulitis, foot infections, and amputation between metformin no-use and use in persons with type 2 diabetes. Methods: Using propensity score matching, we identified 23234 pairs of metformin nonusers and users from the National Health Insurance Research Database of Taiwan, since January 1, 2000, to December 31, 2017. Cox proportional hazards models were adopted to examine the risks of incident cellulitis, recurrent cellulitis, foot infections, and amputation between metformin use and no-use. Results: The mean follow-up period of metformin use and no-use was 6.31 (3.93) and 5.54 (3.97) years, respectively. Compared with metformin no-use, the adjusted hazard ratio and 95% confidence interval for metformin use in cellulitis development, recurrent cellulitis, foot infections, and amputation were 1.08 (1.04-1.12), 1.33 (1.14-1.55), 1.91 (1.75-2.09), and 1.88 (1.35-2.62), respectively. The longer cumulative duration of metformin usage had association with higher risks of these outcomes than metformin no-use. Conclusion: This population-based cohort study revealed that metformin use had association with significantly higher risks of incident cellulitis, recurrent cellulitis, foot infections, and amputation than metformin no-use in patients with type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%

Metformin and the risks of cellulitis, foot infections, and amputation in patients with type 2 diabetes

Yeh,

Yen,

Wei

et al. 2024

Journal of the Chinese Medical Association

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“…This is consistent with our data, where there is a similar trend within these protein levels. Metformin was described to inhibit NF-κB activation in normal cell lines [ 35 , 87 ] senescent cells [ 88 ] and cancer cells [ 89 ]. The main antitumor mechanism seems to be related to reversible inhibition of the mitochondrial complex I function which has also been involved in the hypoxic inhibition of HIF-1α.…”

Section: Discussionmentioning

confidence: 99%

“…The effect requires an intact mitochondrial inner membrane potential. Metformin reduced HIF-1α in colon cancer cells-HCT 116 p53 −/− and significantly diminished downstream HIF dependent proteins like VEGF, and carbonic anhydrase 9 (CA9) in these cells, under hypoxic conditions (1.5% O 2 ), however, it slightly increased HIF-1α, VEGF and CA9 under normal O 2 concentration (21%)[ 87 ].…”

Section: Discussionmentioning

confidence: 99%

“…Cells exposed to Metformin were treated with medium in a similar manner. Since the Metformin inhibition of mithocondrial function is reversible [ 87 ], the time elapsed between exposure and the end of the experiments diminished the Metformin effects and allowed the cells to recover, in the absence of PDT. This could explain the reactive increase of NF-κB activation, HIF-1α and VEGF in groups without PDT.…”

Section: Discussionmentioning

confidence: 99%

“…When combined treatment was used, the angiogenetic markers like VEGF and at a lower extent HIF-1α, although significantly inhibited compared to controls, remained at higher levels, compared to PDT alone. This could be partially explained by the experimental setting, as above, however, this effect might be also due to the stimulatory effect of Metformin on these molecules in normoxic conditions [ 87 ]. In melanoma, induction of melanogenesis was shown to increase HIF-1α and stimulate the expression of several downstream HIF-1 regulated genes, including VEGF.…”

Section: Discussionmentioning

confidence: 99%

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Combined regimen of photodynamic therapy mediated by Gallium phthalocyanine chloride and Metformin enhances anti-melanoma efficacy

et al. 2017

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BackgroundMelanoma therapy is challenging, especially in advanced cases, due to multiple developed tumor defense mechanisms. Photodynamic therapy (PDT) might represent an adjuvant treatment, because of its bimodal action: tumor destruction and immune system awakening. In this study, a combination of PDT mediated by a metal substituted phthalocyanine—Gallium phthalocyanine chloride (GaPc) and Metformin was used against melanoma. The study aimed to: (1) find the anti-melanoma efficacy of GaPc-PDT, (2) assess possible beneficial effects of Metformin addition to PDT, (3) uncover some of the mechanisms underlining cell killing and anti-angiogenic effects.MethodsTwo human lightly pigmented melanoma cell lines: WM35 and M1/15 subjected to previous Metformin exposure were treated by GaPc-PDT. Cell viability, death mechanism, cytoskeleton alterations, oxidative damage, were assessed by means of colorimetry, flowcytometry, confocal microscopy, spectrophotometry, ELISA, Western Blotting.ResultsGaPc proved an efficient photosensitizer. Metformin addition enhanced cell killing by mechanisms dependent on the cell line, namely apoptosis in the metastatic M1/15 and necrosis in the radial growth phase, WM35. Cell death mechanism relied on the inhibition of nuclear transcription factor (NF)-κB activation and tumor necrosis factor (TNF)—related apoptosis-inducing ligand (TRAIL) sensitization, leading to TRAIL and TNF-α induced apoptosis. Metformin diminished the anti-angiogenic effect of PDT.ConclusionsMetformin addition to GaPc-PDT increased tumor cell killing through enhanced oxidative damage and induction of proapoptotic mechanisms, but altered PDT anti-angiogenic effects.General significanceCombination of Metformin and PDT might represent a solution to enhance the efficacy, leading to a potential adjuvant role of PDT in melanoma therapy.

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Antidiabetic drug metformin affects the developmental competence of cleavage-stage embryos

Nayak

Salian

Agarwal

et al. 2020

J Assist Reprod Genet

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Correction: Metformin Induces Cell Cycle Arrest, Reduced Proliferation, Wound Healing Impairment In Vivo and Is Associated to Clinical Outcomes in Diabetic Foot Ulcer Patients

Cited by 5 publications

References 1 publication

Metformin and the risks of cellulitis, foot infections, and amputation in patients with type 2 diabetes

Metformin and the risks of cellulitis, foot infections, and amputation in patients with type 2 diabetes

Combined regimen of photodynamic therapy mediated by Gallium phthalocyanine chloride and Metformin enhances anti-melanoma efficacy

Antidiabetic drug metformin affects the developmental competence of cleavage-stage embryos

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