Plumbagin Elicits Cell-Specific Cytotoxic Effects and Metabolic Responses in Melanoma Cells

Abstract

Melanoma is one of the most malignant skin cancers that require comprehensive therapies, including chemotherapy. A plant-derived drug, plumbagin (PLB), exhibits an anticancer property in several cancers. We compared the cytotoxic and metabolic roles of PLB in A375 and SK-MEL-28 cells, each with different aggressiveness. In our results, they were observed to have distinctive mitochondrial respiratory functions. The primary reactive oxygen species (ROS) source of A375 can be robustly attenuated by cell membrane permeabilization. A375 cell viability and proliferation, migration, and apoptosis induction are more sensitive to PLB treatment. PLB induced metabolic alternations in SK-MEL-28 cells, which included increasing mitochondrial oxidative phosphorylation (OXPHOS), mitochondrial ATP production, and mitochondrial mass. Decreasing mitochondrial OXPHOS and total ATP production with elevated mitochondrial membrane potential (MMP) were observed in PLB-induced A375 cells. PLB also induced ROS production and increased proton leak and non-mitochondria respiration in both cells. This study reveals the relationship between metabolism and cytotoxic effects of PLB in melanoma. PLB displays stronger cytotoxic effects on A375 cells, which exhibit lower respiratory function than SK-MEL-28 cells with higher respiratory function, and triggers cell-specific metabolic changes in accordance with its cytotoxic effects. These findings indicate that PLB might serve as a promising anticancer drug, targeting metabolism.

Mitochondria-Targeted Drug Delivery

“…Indeed, PLB displays stronger cytotoxic effects on A375 cells, which exhibit lower respiratory function than SK-MEL-28 cells with higher respiratory function. At contrary to SK-MEL-28, A375 cells after the treatment with PLB have decreased mitochondrial OXPHOS and ATP production with elevated mitochondrial membrane potential [9]. Similar results were obtained by Zavadskis et al using human amniotic membrane mesenchymal stromal cells (hAMSCs), human bone marrow mesenchymal stromal cells (hBMSCs) and MG-63 cells.…”

“…In conclusion, this Special Issue underlines importance of mitochondria in pathophysiological situation such as: genetic disorders [1,2], cardiovascular diseases [3,4], inflammation [5] and cancer [6][7][8][9][10]. Indicates new tools to selective target mitochondria in order to: rescue aberrant cell phenotype, change cell metabolism or induces mitochondria dependent cell death [1][2][3][4][5][6][7][8][9][10][11][12].…”

Assessment of the in Vitro Antimelanoma Potential of Lippia microphylla Cham (Verbenaceae) Essential Oil

“…Multidisciplinary approaches, including chemotherapy, immunotherapy, and radiotherapy, are performed in advanced cases to improve the prognosis, given that advanced melanomas exhibit high aggressiveness and metastatic characteristics. [8,9] Natural products constitute one of the most important sources of potential antitumor drugs, accounting for more than 60 % of clinically approved anticancer drugs used in therapy. [10] such as paclitaxel from the Taxus genus, vincristine, and vinblastine from Catharanthus roseus, which are clinically used anticancer drugs.…”

“…Surgery is generally considered the typical treatment for localized melanoma. Multidisciplinary approaches, including chemotherapy, immunotherapy, and radiotherapy, are performed in advanced cases to improve the prognosis, given that advanced melanomas exhibit high aggressiveness and metastatic characteristics [8,9] …”

Pharmacokinetics of Herb-Drug Interactions of Plumbagin and Tazemetostat in Rats by UPLC-MS/MS

“… 6 PLB displays stronger cytotoxic effects on A375 cells, which exhibit lower respiratory function than SK-MEL-28 cells with higher respiratory function, and triggers cell-specific metabolic changes in accordance with its cytotoxic effects. 7 PLB is cytotoxic for cancer cells due to its ability to trigger reactive oxygen species (ROS) formation and subsequent apoptosis. PLB may inhibit the differentiation of bone resorbing osteoclasts in cancer-related models.…”