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      Antiproliferative activity and apoptosis-inducing mechanism of Curcuma longa (Turmimax®) on HeLa cell lines Translated title: Atividade antiproliferativa e mecanismo indutor de apoptose de Curcuma longa (Turmimax®) em HeLa

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          Abstract

          Abstract Curcumin, the primary polyphenol found in turmeric, is derived from the Curcuma longa plant. Since curcumin is nontoxic and has a wide range of medicinal qualities, including anti-oxidant, analgesic, anti-inflammatory, and antibacterial action, it has been widely employed in Ayurveda medicine for ages. Curcumin has recently been discovered to have anti-cancer properties through its impact on numerous biological pathways involved in carcinogenesis, metastasis, tumorigenesis, cell cycle regulation, mutagenesis, and oncogene expression. In this study, we determined the Antiproliferative activity and apoptosis-inducing mechanism of C. longa (Turmimax®) on human cancer cells. The cytotoxic effect was evaluated against HeLa cell lines using the MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. Flow cytometric analysis was performed to detect apoptotic cell death. Turmimax® exhibits promising properties as a potential anti-cancer therapeutic agent in human cervical adenocarcinomas and possibly other cancer types, with an IC50 value of 87.89 µg/mL. In HeLa cells treated with Turmimax®, cell cycle arrest was seen in the G0/G1 and S phases. By inducing apoptosis and increasing the number of apoptotic cells in a dose-dependent manner, the experimental data suggest that Turmimax® has considerable promise in cancer prevention and treatment.

          Translated abstract

          Resumo A curcumina, o polifenol primário encontrado no açafrão, é derivada da planta Curcuma longa. Como a curcumina não é tóxica e possui ampla gama de qualidades medicinais, incluindo ação antioxidante, analgésica, anti-inflamatória e antibacteriana, ela tem sido muito empregada na medicina ayurvédica há séculos. Descobriu-se recentemente que a curcumina possui propriedades anticancerígenas por meio de seu impacto em várias vias biológicas envolvidas na carcinogênese, metástase, tumorigênese, regulação do ciclo celular, mutagênese e expressão de oncogenes. Neste estudo, determinamos a atividade antiproliferativa e o mecanismo de indução de apoptose de C. longa (Turmimax®) em células cancerígenas humanas. O efeito citotóxico foi avaliado em linhagens de células HeLa usando o ensaio MTT - brometo de 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazólio. Uma análise de citometria de fluxo foi realizada para detectar a morte celular apoptótica. Turmimax® exibe propriedades promissoras como um potencial agente terapêutico anticancerígeno em adenocarcinomas cervicais humanos e possivelmente em outros tipos de câncer, com um valor de IC50 de 87,89 µg/mL. Nas células HeLa tratadas com Turmimax®, a parada do ciclo celular foi observada nas fases G0/G1 e S. Ao induzir a apoptose e aumentar o número de células apoptóticas de maneira dependente da dose, os dados experimentais sugerem que Turmimax® tem uma indicação considerável na prevenção e tratamento do câncer.

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          Most cited references18

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          The Hallmarks of Cancer

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            Anticancer potential of curcumin: preclinical and clinical studies.

            Curcumin (diferuloylmethane) is a polyphenol derived from the plant Curcuma longa, commonly called turmeric. Extensive research over the last 50 years has indicated this polyphenol can both prevent and treat cancer. The anticancer potential of curcumin stems from its ability to suppress proliferation of a wide variety of tumor cells, down-regulate transcription factors NF-kappa B, AP-1 and Egr-1; down-regulate the expression of COX2, LOX, NOS, MMP-9, uPA, TNF, chemokines, cell surface adhesion molecules and cyclin D1; down-regulate growth factor receptors (such as EGFR and HER2); and inhibit the activity of c-Jun N-terminal kinase, protein tyrosine kinases and protein serine/threonine kinases. In several systems, curcumin has been described as a potent antioxidant and anti-inflammatory agent. Evidence has also been presented to suggest that curcumin can suppress tumor initiation, promotion and metastasis. Pharmacologically, curcumin has been found to be safe. Human clinical trials indicated no dose-limiting toxicity when administered at doses up to 10 g/day. All of these studies suggest that curcumin has enormous potential in the prevention and therapy of cancer. The current review describes in detail the data supporting these studies.
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              Apoptotic cell signaling in cancer progression and therapy.

              Apoptosis is a tightly regulated cell suicide program that plays an essential role in the development and maintenance of tissue homeostasis by eliminating unnecessary or harmful cells. Impairment of this native defense mechanism promotes aberrant cellular proliferation and the accumulation of genetic defects, ultimately resulting in tumorigenesis, and frequently confers drug resistance to cancer cells. The regulation of apoptosis at several levels is essential to maintain the delicate balance between cellular survival and death signaling that is required to prevent disease. Complex networks of signaling pathways act to promote or inhibit apoptosis in response to various cues. Apoptosis can be triggered by signals from within the cell, such as genotoxic stress, or by extrinsic signals, such as the binding of ligands to cell surface death receptors. Various upstream signaling pathways can modulate apoptosis by converging on, and thereby altering the activity of, common central control points within the apoptotic signaling pathways, which involve the BCL-2 family proteins, inhibitor of apoptosis (IAP) proteins, and FLICE-inhibitory protein (c-FLIP). This review highlights the role of these fundamental regulators of apoptosis in the context of both normal apoptotic signaling mechanisms and dysregulated apoptotic pathways that can render cancer cells resistant to cell death. In addition, therapeutic strategies aimed at modulating the activity of BCL-2 family proteins, IAPs, and c-FLIP for the targeted induction of apoptosis are briefly discussed.

                Author and article information

                Journal
                bjb
                Brazilian Journal of Biology
                Braz. J. Biol.
                Instituto Internacional de Ecologia (São Carlos, SP, Brazil )
                1519-6984
                1678-4375
                2023
                : 83
                : e275953
                Affiliations
                [01] Bangalore Karnataka orgnameStar Hi Herbs Pvt Ltd India
                Article
                S1519-69842023000100859 S1519-6984(23)08300000859
                10.1590/1519-6984.275953
                37820211
                4b975cf1-b97e-4ed5-914c-753fd58f2e8b

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 02 August 2023
                : 26 June 2023
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 18, Pages: 0
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                SciELO Brazil

                Categories
                Original Article

                antiproliferativo,apoptosis,HeLa cell lines,Curcuma longa,antiproliferative,apoptose,linhas de células HeLa

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