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1.
Can J Physiol Pharmacol ; 100(8): 806-817, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35704944

RESUMO

Chemotherapeutic resistance can limit breast cancer outcomes; therefore, the exploration of novel therapeutic options is warranted. Isolated compounds found in cannabis have previously been shown to exhibit anti-cancer effects, but little is known about their effects in resistant breast cancer. Our study aimed to evaluate the effects of terpenes found in cannabis in in vitro chemotherapy-resistant model of breast cancer. We aimed to identify whether five terpenes found in cannabis produced anti-cancer effects, and whether their effects were improved upon co-treatment with cannabinoids and flavonoids also found in cannabis. Nerolidol and ß-caryophyllene produced the greatest cytotoxic effects, activated the apoptotic cascade, and reduced cellular invasion. Combinations with the flavonoid kaempferol potentiated the cytotoxic effects of ocimene, terpinolene, and ß-myrcene. Combinations of nerolidol and Δ9-tetrahydrocannabinol or cannabidiol produced variable responses ranging from antagonism and additivity to synergy, depending on concentrations used. Our results indicate that cannabis terpenes, alone or combined with cannabinoids and flavonoids, produced anti-cancer effects in chemotherapy-resistant breast cancer cell lines. This study is a first step in the identification of compounds that could have therapeutic potential in the treatment of resistant breast cancer.


Assuntos
Antineoplásicos , Neoplasias da Mama , Canabinoides , Cannabis , Neoplasias da Mama/tratamento farmacológico , Agonistas de Receptores de Canabinoides , Canabinoides/farmacologia , Canabinoides/uso terapêutico , Feminino , Flavonoides , Humanos , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Terpenos/farmacologia , Terpenos/uso terapêutico
2.
Inflamm Res ; 70(5): 525-538, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33721031

RESUMO

As an integral part of the innate immune system, the epithelial membrane is exposed to an array of insults that may trigger an immune response. One of the immune system's main functions is to regulate the level of communications between the mucosa and the lumen of various tissues. While it is clear that inhaled or ingested substances, or microorganisms may induce changes that affect the epithelial barrier in various ways, the proteins involved in the signaling cascades and physiological events leading to the regulation and maintenance of the barrier are not always well characterized. We review here some of the signaling components involved in regulating the barrier's paracellular permeability, and their potential effects on the activation of an immune response. While an effective immune response must be launched against pathogenic insults, tolerance must also be maintained for non-pathogenic antigens such as those in the commensal flora or for endogenous metabolites. Along with other members of the innate and adaptive immunity, the endocannabinoid system also plays an instrumental role in maintaining the balance between inflammation and tolerance. We discuss the potential effects of endo- and phytocannabinoids on epithelial permeability and how the dysregulation of this system could be involved in diseases and targeted for therapy.


Assuntos
Células Epiteliais/metabolismo , Junções Aderentes/metabolismo , Animais , Polaridade Celular , Humanos , Permeabilidade , Junções Íntimas/metabolismo
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