Cancer is one of the most common causes of death worldwide. Although chemotherapy remains one of the most important treatments, its efficacy is limited by drug resistance and drug induced-toxicity. Due to the limited therapeutic efficacy of monotherapy, current clinical practice for treating cancer includes the co-administration of more drugs acting at multiple molecular levels, as well as addressing the same target through different mechanisms of actions, to maximize efficacy, minimize toxicity, and overcome resistance. In this scenario, curcumin, a yellow pigment from Curcuma longa, has been reported for its potential chemopreventive and chemotherapeutic activity in different kinds of cancer. Herein we explored the in vitro effects of curcumin in combination with paclitaxel (PTX) in a model of glioblastoma (GBM) using rat C6 glioma cells, or with carfilzomib (CFZ) in a model of multiple myeloma (MM) using U266 cells. Curcumin significantly improved cytotoxic effects of PTX and CFZ. These effects were confirmed by clonogenic assay (in GBM model) and G0/G1 cell cycle arrest. Curcumin alone did not affect proteasome at the tested dose in the MM model, supporting the involvement of different mechanisms in the observed effects. In both C6 and U266 cell lines we found constitutive activation of NF-κB (a transcription factor involved in cell proliferation, apoptosis, and metastasis) that was inhibited by PTX or CFZ, and curcumin. Interestingly, the combination of the single drugs with curcumin strongly inhibited NF-κB nuclear translocation and reduced IκB phosphorylation. Results also support the involvement of p53-p21 axis in the anticancer effects of curcumin, PTX and CFZ. Combination of the single drugs with curcumin further increased p53 and p21 levels enhancing their antiproliferative effects. Furthermore, curcumin enhanced PTX and CFZ proapoptotic effect with activation of caspase-3, and reduced expression of the anti-apoptotic protein Bcl-2. Altogether, the present data demonstrated that curcumin can ameliorate efficacy of PTX and CFZ in two different models of GBM and MM respectively, thus suggesting that combination of curcumin with a first line antineoplastic drug could represent a valuable strategy to obtain an amplified response with minimized side effects.

In vitro studies on curcumin efficacy in cancer combination therapy.

Antonio Speciale
2018-01-01

Abstract

Cancer is one of the most common causes of death worldwide. Although chemotherapy remains one of the most important treatments, its efficacy is limited by drug resistance and drug induced-toxicity. Due to the limited therapeutic efficacy of monotherapy, current clinical practice for treating cancer includes the co-administration of more drugs acting at multiple molecular levels, as well as addressing the same target through different mechanisms of actions, to maximize efficacy, minimize toxicity, and overcome resistance. In this scenario, curcumin, a yellow pigment from Curcuma longa, has been reported for its potential chemopreventive and chemotherapeutic activity in different kinds of cancer. Herein we explored the in vitro effects of curcumin in combination with paclitaxel (PTX) in a model of glioblastoma (GBM) using rat C6 glioma cells, or with carfilzomib (CFZ) in a model of multiple myeloma (MM) using U266 cells. Curcumin significantly improved cytotoxic effects of PTX and CFZ. These effects were confirmed by clonogenic assay (in GBM model) and G0/G1 cell cycle arrest. Curcumin alone did not affect proteasome at the tested dose in the MM model, supporting the involvement of different mechanisms in the observed effects. In both C6 and U266 cell lines we found constitutive activation of NF-κB (a transcription factor involved in cell proliferation, apoptosis, and metastasis) that was inhibited by PTX or CFZ, and curcumin. Interestingly, the combination of the single drugs with curcumin strongly inhibited NF-κB nuclear translocation and reduced IκB phosphorylation. Results also support the involvement of p53-p21 axis in the anticancer effects of curcumin, PTX and CFZ. Combination of the single drugs with curcumin further increased p53 and p21 levels enhancing their antiproliferative effects. Furthermore, curcumin enhanced PTX and CFZ proapoptotic effect with activation of caspase-3, and reduced expression of the anti-apoptotic protein Bcl-2. Altogether, the present data demonstrated that curcumin can ameliorate efficacy of PTX and CFZ in two different models of GBM and MM respectively, thus suggesting that combination of curcumin with a first line antineoplastic drug could represent a valuable strategy to obtain an amplified response with minimized side effects.
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/3128418
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact