Curcumin promotes apoptosis of human melanoma cells by caspase 3

• Published in: Cell biochemistry and function Vol. 41; no. 8; pp. 1295 - 1304
• Main Authors: Manica, Daiane, Silva, Gilnei Bruno da, Silva, Alana Patrícia da, Marafon, Filomena, Maciel, Sarah Franco Vieira de Oliveira, Bagatini, Margarete Dulce, Moreno, Marcelo
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.12.2023
• Subjects: Annexin V; Apoptosis; Assaying; Caspase-3; Cell adhesion & migration; Cell death; Cell migration; Cell viability; Curcumin; Enzymatic activity; Flow cytometry; Fluorescence; Fluorescence microscopy; Gene expression; Melanoma; Metastases; Metastasis; natural compound; Nitric oxide; Oxidants; Oxidative stress; Oxidizing agents; Polymerase chain reaction; polyphenol; Polyphenols; Reactive oxygen species; Reverse transcription; skin cancer; Thiols; Wound healing; skin cancer; apoptosis; polyphenol; oxidative stress; natural compound
• ISSN: 0263-6484; 1099-0844
• DOI: 10.1002/cbf.3863

Cutaneous melanoma (CM) is a malignant neoplasm with a high metastatic rate that shows poor response to systemic treatments in patients with advanced stages. Recently, studies have highlighted the antineoplastic potential of natural compounds, such as polyphenols, in the adjuvant therapy context to treat CM. The objective of the present study was to evaluate the effect of different concentrations of curcumin (0.1–100 µM) on the metastatic CM cell line SK‐MEL‐28. The cells were treated for 6 and 24 h with different concentrations of curcumin. Cell viability was assessed by 3‐(4,5‐dimethyl‐2thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) assay and fluorescence microscopy. The apoptotic‐inducing potential was detected by annexin V flow cytometry. The wound healing assay was used to verify cell migration after the curcumin exposition. The redox profile was evaluated by levels of the pro‐oxidant markers reactive oxygen species (ROS) and Nitric oxide (NOx) and antioxidants of total thiols (PSH) and nonprotein thiols. The gene expression and enzymatic activity of caspase 3 were evaluated by reverse transcription‐quantitative polymerase chain reaction and a sensitive fluorescence assay, respectively. Curcumin significantly decreased the cell viability of SK‐MEL‐28 cells at both exposure times. It also induced apoptosis at the highest concentration tested (p < .0001). SK‐MEL‐28 cell migration was inhibited by curcumin after treatment with 10 µM (p < .0001) and 100 µM (p < .0001) for 6 and 24 h (p = .0006 and p < .0001, respectively). Furthermore, curcumin significantly increased levels of ROS and NOx. Finally, curcumin was capable of increasing the gene expression at 10 µM (p = .0344) and 100 µM (p = .0067) and enzymatic activity at 10 µM (p = .0086) and 100 µM (p < .0001) of caspase 3 after 24 h. For the first time, we elucidated in our study that curcumin increases ROS levels, promoting oxidative stress that activates the caspase pathway and culminates in SK‐MEL‐28 metastatic CM cell death. Significance statement Cutaneous melanoma (CM) is an aggressive and lethal type of cancer. Many individuals do not respond completely to available treatments, increasing metastasis and death rates. In SK‐MEL‐28 CM metastatic cells, curcumin caused caspase 3‐associated apoptosis after treatment with different concentrations. Therefore, in this study, we found that curcumin showed promising results, proving an option for adjuvant therapy.