Background-
Gastric adenocarcinoma can be characterised as a malignant epithelial tumour that originates from the glandular epithelium of the gastric mucosa. Gastric cancer (GC) is one of the most prevalent human malignancies and the third most common cause of cancer‐related death worldwide.
Doxorubicin is an anthracycline antibiotic, which is used in the treatment of GC. This drug exerts its anticancer effects by inhibiting cell division and induction of apoptosis. However, the therapeutic efficacy of doxorubicin is significantly decreased in drug‐resistant cancer cells.
Curcumin, a diarylheptanoid isolated from rhizomes of Turmeric (Curcuma longa Family- Zingiberaceae), has been reported to have anticancer activity with low toxicity. It targets several cellular processes involved in cell death such as transcription factors, cytokines, kinases, induction of apoptotic pathways, cell cycle arrest, and regulation of various transduction pathways, such as regulation of AMPK, NF‐κB, Akt, β‐catenin, MAPK, p53, JAK/STAT, Nrf2, Notch‐1.
The overexpression of efflux transporters results in the excretion of doxorubicin from cancer cells thereby decreasing intracellular levels and therapeutic efficacy of doxorubicin in drug‐resistant cancer cells. In addition, the apoptotic pathways are inhibited in most drug‐resistant cancer cells indicating decreased anticancer activity of doxorubicin in such cells. The several molecular processes involved in apoptotic dysregulation, such as reinforcement of survival signals (NF‐κB, survivin, etc.), inactivation of proapoptotic factors (p53, Bax, Caspase 9, etc.), and activation of antiapoptotic factors (Bcl‐2, Bfl1/A1, etc.)
Research and Results-
Studies that show a comparison of anti-cancer activities of Doxorubicin, Curcumin and Dox-Cur reveal morphological alterations including membrane damage, fragmented nuclei, decreased cell size, and cell shrinkage. The morphological alterations in treated cells with Dox‐Cur were significantly more than in doxorubicin and curcumin groups. (Figure A)
Curcumin, doxorubicin, and Dox‐Cur significantly decreased the migration and invasion of GC cells in a concentration‐dependent manner. However, the inhibition of migration and invasion in the cells treated with Dox‐Cur was significantly more as compared with curcumin and doxorubicin.
The expression of apoptosis-related genes was evaluated using real-time PCR analysis. It was reported that Dox-Cur treatment significantly increased mRNA expression of BAX and CAS9 genes (pro-apoptotic genes) in GC cells and decreased expression of the BCL-2 gene (anti-apoptotic gene). Thus, the Dox-Cur regimen synergistically resulted in favour of the apoptotic pattern of BCL-2 and BAX expression suggesting a significant increase in apoptotic and antimetastatic activity as compared to only doxorubicin. (Figure B)
This study suggested that Doxorubicin with appropriate quantities of Curcumin in a favourable formulation may be effective in breaking the drug resistance in Gastric Adenocarcinoma and beneficial for the treatment of doxorubicin-resistant GC patients.
References-
“Enhanced anticancer potency of doxorubicin in combination with curcumin in gastric adenocarcinoma”- DOI: 10.1002/jbt.22486
By Debangana Banerjee
Comments