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Avaliação do potencial anticancerígeno do canabidiol em células do carcinoma renal humano
| Name: | Description: | Size: | Format: | |
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| Projeto de pós-graduação_39766 | 1.2 MB | Adobe PDF |
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Abstract(s)
O canabidiol (CBD), principal canabinoide não psicotrópico da Cannabis sativa, possui diversas ações farmacológicas com potencial terapêutico, incluindo efeitos antitumorais. Contudo, o seu efeito específico no carcinoma de células renais (CCR) é ainda desconhecido. Para preencher esta lacuna de conhecimento, este trabalho teve como principal objetivo avaliar o potencial antitumoral do CBD em células do carcinoma renal humano. Reconhecendo que as condições de cultura celular, particularmente a presença de soro no meio de cultura, podem modular os efeitos antitumorais dos canabinoides, a potencial influência deste suplemento de crescimento na resposta ao CBD foi igualmente explorada. Assim, o perfil citotóxico do CBD foi avaliado em linhas celulares renais humanas tumorais (Caki-1 e 769-P) e não tumorais (HK-2), utilizando meio isento de soro bovino fetal (FBS) ou contendo 5% deste suplemento. As células Caki-1, 769-P e HK-2 foram expostas a uma ampla gama de concentrações de CBD (1-100 μM) a diferentes tempos de exposição. Neste trabalho foram avaliados parâmetros como a viabilidade celular, o efeito antiproliferativo e a formação de espécies reativas de oxigénio (ROS). Os resultados revelaram que o CBD induziu uma diminuição da viabilidade celular de modo dependente da concentração em todas as linhas e condições testadas. Após 24 horas de exposição em meio contendo soro, verificou-se que as células HK-2 e Caki-1 eram as mais sensíveis à toxicidade do CBD, seguidas pelas células 769-P (os valores de IC50 foram, respetivamente, 14,5, 14,8 e 20,1 μM; p=0,0052). Na ausência de soro, os valores de IC50 diminuíram significativamente (5,2, 6,9 e 6,8 μM para células HK-2, Caki-1 e 769-P, respetivamente), demonstrando que a presença de soro diminuiu substancialmente a sensibilidade celular ao CBD. Os valores de IC50 obtidos após 48h foram semelhantes, indicando que este efeito não é dependente do tempo de exposição. Foi ainda observado que o CBD inibiu a proliferação de todas as linhas estudadas, de forma mais significativa para as Caki-1 e 769-P, na ausência de soro após 48 e 72 horas, como também na presença de soro, apenas para 769-P, para os mesmos tempos de exposição. Adicionalmente, verificou-se que o CBD induziu stress oxidativo em todas as linhas celulares, com um aumento estatisticamente significativo da formação de ROS, para as concentrações de 10 e 15 μM às 24 e 48 horas. Em conclusão, o CBD demonstrou efeito antitumoral in vitro em células do CCR, com maior eficácia na ausência de soro. No entanto, a citotoxicidade do CBD não foi seletiva para células tumorais, o que pode ser uma limitação significativa ao seu uso seguro na prática clínica.
Cannabidiol (CBD), the main non-psychoactive cannabinoid from Cannabis sativa, has various pharmacological actions with therapeutic potential, including antitumor effects. However, its specific effect on renal cell carcinoma (RCC) remains unknown. To fill this knowledge gap, the primary aim of this study was to evaluate the anticancer potential of CBD in human renal carcinoma cells. Recognizing that cell culture conditions, particularly the presence of serum in the culture medium, can modulate the antitumor effects of cannabinoids, the potential influence of this growth supplement on CBD response was also explored. Thus, the cytotoxic profile of CBD was assessed in human renal tumor cell lines (Caki-1 and 769-P) and non-tumor cell lines (HK-2), using media free of fetal bovine serum (FBS) or containing 5% of this supplement. Caki-1, 769-P, and HK-2 cells were exposed to a wide range of CBD concentrations (1–100 μM) at different exposure times. Parameters such as cell viability, antiproliferative effect, and reactive oxygen species (ROS) formation were evaluated in this study. The results revealed that CBD induced a concentration-dependent decrease in cell viability across all tested lines and conditions. After 24 hours of exposure in serum-containing medium, HK-2 and Caki-1 cells were found to be the most sensitive to CBD toxicity, followed by 769-P cells (IC50 values were 14.5, 14.8, and 20.1 μM, respectively; p=0.0052). In the absence of serum, IC50 values significantly decreased (5.2, 6.9, and 6.8 μM for HK-2, Caki-1, and 769-P cells, respectively), demonstrating that the presence of serum substantially reduced cellular sensitivity to CBD. IC50 values obtained after 48 hours were similar, indicating that this effect is not dependent on exposure time. Furthermore, CBD inhibited the proliferation of all studied cell lines, most notably for Caki-1 and 769-P in the absence of serum after 48 and 72 hours, and for 769-P in the presence of serum for the same exposure times. Additionally, it was observed that CBD induced oxidative stress in all cell lines, with a statistically significant increase in ROS formation at concentrations of 10 and 15 μM at 24 and 48 hours. In conclusion, CBD demonstrated an in vitro antitumor effect on RCC cells, with greater efficacy in the absence of serum. However, CBD cytotoxicity was not selective for tumor cells, which could pose a significant limitation to its safe clinical use.
Cannabidiol (CBD), the main non-psychoactive cannabinoid from Cannabis sativa, has various pharmacological actions with therapeutic potential, including antitumor effects. However, its specific effect on renal cell carcinoma (RCC) remains unknown. To fill this knowledge gap, the primary aim of this study was to evaluate the anticancer potential of CBD in human renal carcinoma cells. Recognizing that cell culture conditions, particularly the presence of serum in the culture medium, can modulate the antitumor effects of cannabinoids, the potential influence of this growth supplement on CBD response was also explored. Thus, the cytotoxic profile of CBD was assessed in human renal tumor cell lines (Caki-1 and 769-P) and non-tumor cell lines (HK-2), using media free of fetal bovine serum (FBS) or containing 5% of this supplement. Caki-1, 769-P, and HK-2 cells were exposed to a wide range of CBD concentrations (1–100 μM) at different exposure times. Parameters such as cell viability, antiproliferative effect, and reactive oxygen species (ROS) formation were evaluated in this study. The results revealed that CBD induced a concentration-dependent decrease in cell viability across all tested lines and conditions. After 24 hours of exposure in serum-containing medium, HK-2 and Caki-1 cells were found to be the most sensitive to CBD toxicity, followed by 769-P cells (IC50 values were 14.5, 14.8, and 20.1 μM, respectively; p=0.0052). In the absence of serum, IC50 values significantly decreased (5.2, 6.9, and 6.8 μM for HK-2, Caki-1, and 769-P cells, respectively), demonstrating that the presence of serum substantially reduced cellular sensitivity to CBD. IC50 values obtained after 48 hours were similar, indicating that this effect is not dependent on exposure time. Furthermore, CBD inhibited the proliferation of all studied cell lines, most notably for Caki-1 and 769-P in the absence of serum after 48 and 72 hours, and for 769-P in the presence of serum for the same exposure times. Additionally, it was observed that CBD induced oxidative stress in all cell lines, with a statistically significant increase in ROS formation at concentrations of 10 and 15 μM at 24 and 48 hours. In conclusion, CBD demonstrated an in vitro antitumor effect on RCC cells, with greater efficacy in the absence of serum. However, CBD cytotoxicity was not selective for tumor cells, which could pose a significant limitation to its safe clinical use.
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Keywords
Canabidiol Carcinoma de células renais Atividade antitumoral Soro Cannabidiol Renal cell carcinoma Antitumor activity Serum