Curcumin aid for drug-defying breast cancer
doi:10.1038/nindia.2011.173 Published online 29 November 2011
Curcurmin may prove handy in overcoming the problem of drug resistance in breast cancer. The multi-faceted compound found in turmeric has shown promise in inducing drug-sensitivity in drug-resistant breast cancer cells thus turning them 'mortal'1.
A joint research team from Bose Institute, Kolkata and National Centre for Cell Science, Pune has claimed that curcumin also reduces drug-induced toxicity.
"We believe that inclusion of curcumin in routine chemotherapy strategies as supportive therapy would prove more successful," says lead researcher Gaurisankar Sa from the Division of Molecular Medicine of Bose Institute. In addition, curcumin also helps avert the toxic effects of doxorubicin, a combination anti-cancer drug, on vital organs such as heart and liver, Sa adds.
Drug resistance, a basic problem of almost all cancers, is a major hurdle in the successful management of highly malignant tumors. Doxorubicin is used to treat a variety of cancers such as blood, breast, ovarian and brain cancers. Growing research shows that various cancers have grown resistant to doxorubicin. One such cancer is breast cancer. Breast cancer grows resistant to doxorubicin due to activation of a protein called nuclear factor k B (NFkB). This activation of NFkB turns off p53 gene that codes for a protein called p53, essential in triggering programmed death of cancer cells.
This is why inhibiting the activity of NFkB is a novel approach to sensitize cancer cells to drugs such as doxorubicin. Previous study by the same research group has shown the involvement of p53 gene in curcumin-induced cancer cells death. However, no studies have been done to probe whether curcumin could help overcome resistance to doxorubicin and its toxic effects on healthy cells through the inhibition of NFkB.
The researchers carried out experiments with cultured Ehrlisch's Ascites carcinoma cells, a type of breast cancer cells grown in mice. The cancer cells were exposed to curcumin and doxorubicin separately. The cells were pre‐treated with curcumin for two hours followed by doxorubicin for 24 hours. Compared to doxorubicin treatment alone, the combination of doxorubicin and curcumin was highly effective in reducing cell survival in drug-resistant cancer cells.
The culture study further found that combination of curcumin and doxorubicin shut down the activity of p65NFkB, a type of NFkB that renders the cancer cells drug-resistant. In addition, it was found that combination of curcumin and doxorubicin activated caspase enzymes (caspase-9 and casepase-3) which triggered mass death of cancer cells.
Next, the researchers carried out animal studies in which mice were injected with cancer cells and allowed to grow for 7 days. Then the mice were given either curcumin or doxorubicin and combination of doxorubicin and curcumin till 21 days. The animals were then sacrificed and studied.
Doxorubicin when treated in combination with curcumin reduced resistant tumor load in mice. The study with mice also showed that curcumin protected liver, immune cells and cardiac tissue against doxorubicin-induced toxicity. "Curcumin could also reverse drug resistance of other types of cancers," says Sa. Studies from his lab have identified the ability of curcumin to revert drug resistance in lung cancer and acute myeloid leukaemia.
"This study has immense importance in future cancer research and treatment," says Chinmay Kumar Panda from the Chittaranjan National Cancer Institute, Kolkata. Though curcumin could reduce the toxicity of the chemotherapeutic drugs for effective management of cancer, this study should be validated in different types of tumor cell lines as well as in different animal tumor systems to see whether curcumin's effect is tissue-specific or effective only on tumors, he told Nature India. "Like curcumin, other natural products should be screened in different tumour systems to find out potential chemicals," he said.
- Sen, G. S. et al. Curcumin enhances the efficacy of chemotherapy by tailoring p65NFkB‐p300 crosstalk in favor of p53‐p300 in breast cancer. J. Biol. Chem. doi: 10.1074/jbc.M111.262295 (2011)