Enhanced anticancer potency of doxorubicin in combination with curcumin in gastric adenocarcinoma.
Fatemeh Firouzi AmoodizajSevda BaghaeifarElham TaheriMahdieh Farhoudi Sefidan JadidMaryam SafiNasrin Seyyed SaniSaba HajazimianAlireza IsazadehDariush ShanehbandiPublished in: Journal of biochemical and molecular toxicology (2020)
Gastric cancer (GC) is one of the prevalent human malignancies and the third most common cause of cancer-related death worldwide. The doxorubicin hydrochloride is one of the important chemotherapeutic anticancer agents, with a limited therapeutic efficacy for treatment of GC. Therefore, taking advantage of synergistic effects by strategies like combination therapy seems appropriate and promising in treatment of GC. The aim of this study was to investigate a novel method to enhance the therapeutic efficacy of doxorubicin (as a chemotherapeutic agent) by co-administration of curcumin (as a bioactive herbal compound) in GC treatment. In the present study, the effects of curcumin, doxorubicin, and their combinations (Dox-Cur) were evaluated on the viability, morphological features, tumor spheroid formation, migration, invasion, and apoptosis of gastric adenocarcinoma cell line (AGS). Moreover, expression levels of BAX, BCL-2, and CASP9 genes were assessed among AGS cells treated with curcumin, doxorubicin, and Dox-Cur. The obtained results showed that all of curcumin, doxorubicin, and Dox-Cur treatments significantly decreased the viability, tumor spheroid formation, migration, and invasion in the GC model cells. Furthermore, apoptosis rates in AGS cells were increased in a concentration- and time-dependent manner in all of the treatment groups. Moreover, the anticancer activity of the Dox-Cur combination was significantly more than curcumin and doxorubicin treatments alone. According to the results, Dox-Cur combination therapy exerts more profound apoptotic and anticancer effects on the AGS cell line than curcumin or doxorubicin monotherapy.
Keyphrases
- combination therapy
- cell cycle arrest
- drug delivery
- induced apoptosis
- cancer therapy
- cell death
- endoplasmic reticulum stress
- oxidative stress
- squamous cell carcinoma
- endothelial cells
- radiation therapy
- gene expression
- signaling pathway
- poor prognosis
- cell proliferation
- replacement therapy
- pi k akt
- locally advanced
- tissue engineering