TY - JOUR
T1 - Lysicamine Reduces Protein Kinase B (AKT) Activation and Promotes Necrosis in Anaplastic Thyroid Cancer
AU - Rodrigues, Mariana Teixeira
AU - Michelli, Ana Paula Picaro
AU - Caso, Gustavo Felisola
AU - de Oliveira, Paloma Ramos
AU - Rodrigues-Junior, Dorival Mendes
AU - Morale, Mirian Galliote
AU - Machado Júnior, Joel
AU - Bortoluci, Karina Ramalho
AU - Tamura, Rodrigo Esaki
AU - da Silva, Tamiris Reissa Cipriano
AU - Raminelli, Cristiano
AU - Chau, Eric
AU - Godin, Biana
AU - Calil-Silveira, Jamile
AU - Rubio, Ileana G.Sanchez
N1 - Funding Information:
This research was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), grants numbers: IGSR 2014/24549-4, IGSR 2023/02690-6, and RET: 2019/15619-2.
Funding Information:
We gratefully acknowledge the generous funding and resources that enabled our research. Our deep appreciation goes to the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for their support via a doctoral scholarship and international training for Mariana Teixeira Rodrigues and a master scholarship for Paloma R. de Oliveira. Special thanks are extended to Sérgio Schenkman for facilitating our access to the flow cytometer and microplate reader and to Adriana Carmona and Thaysa Paschoalin for using the microscope acquired with resources from FAPESP Grant 2009/53840-0. Our gratitude further extends to Edna Kimura for her generous donation of essential cell lines, significantly enhancing our research success. These contributions and resources played a pivotal role in the accomplishment of our research.
Publisher Copyright:
© 2023 by the authors.
PY - 2023/12
Y1 - 2023/12
N2 - Anaplastic thyroid cancer (ATC) is an aggressive form of thyroid cancer (TC), accounting for 50% of total TC-related deaths. Although therapeutic approaches against TC have improved in recent years, the survival rate remains low, and severe adverse effects are commonly reported. However, unexplored alternatives based on natural compounds, such as lysicamine, an alkaloid found in plants with established cytotoxicity against breast and liver cancers, offer promise. Therefore, this study aimed to explore the antineoplastic effects of lysicamine in papillary TC (BCPAP) and ATC (HTH83 and KTC-2) cells. Lysicamine treatment reduced cell viability, motility, colony formation, and AKT activation while increasing the percentage of necrotic cells. The absence of caspase activity confirmed apoptosis-independent cell death. Necrostatin-1 (NEC-1)-mediated necrosome inhibition reduced lysicamine-induced necrosis in KTC-2, suggesting necroptosis induction via a reactive oxygen species (ROS)-independent mechanism. Additionally, in silico analysis predicted lysicamine target proteins, particularly those related to MAPK and TGF-β signaling. Our study demonstrated lysicamine’s potential as an antineoplastic compound in ATC cells with a proposed mechanism related to inhibiting AKT activation and inducing cell death.
AB - Anaplastic thyroid cancer (ATC) is an aggressive form of thyroid cancer (TC), accounting for 50% of total TC-related deaths. Although therapeutic approaches against TC have improved in recent years, the survival rate remains low, and severe adverse effects are commonly reported. However, unexplored alternatives based on natural compounds, such as lysicamine, an alkaloid found in plants with established cytotoxicity against breast and liver cancers, offer promise. Therefore, this study aimed to explore the antineoplastic effects of lysicamine in papillary TC (BCPAP) and ATC (HTH83 and KTC-2) cells. Lysicamine treatment reduced cell viability, motility, colony formation, and AKT activation while increasing the percentage of necrotic cells. The absence of caspase activity confirmed apoptosis-independent cell death. Necrostatin-1 (NEC-1)-mediated necrosome inhibition reduced lysicamine-induced necrosis in KTC-2, suggesting necroptosis induction via a reactive oxygen species (ROS)-independent mechanism. Additionally, in silico analysis predicted lysicamine target proteins, particularly those related to MAPK and TGF-β signaling. Our study demonstrated lysicamine’s potential as an antineoplastic compound in ATC cells with a proposed mechanism related to inhibiting AKT activation and inducing cell death.
KW - akt phosphorylation
KW - anaplastic thyroid cancer
KW - lysicamine
KW - natural compounds
KW - necrosis
KW - thyroid cancer
UR - http://www.scopus.com/inward/record.url?scp=85180696845&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85180696845&partnerID=8YFLogxK
U2 - 10.3390/ph16121687
DO - 10.3390/ph16121687
M3 - Article
AN - SCOPUS:85180696845
SN - 1424-8247
VL - 16
JO - Pharmaceuticals
JF - Pharmaceuticals
IS - 12
M1 - 1687
ER -