Curcumin, commonly known as Turmeric is a common household spice in our country. Curcuma longa L is a member of the ginger family and its powder is yellow coloured. It was first isolated in 1870 contains diferuloylmethane. Its anti-cancer property could be used in lung metastases, breast cancer, colon cancer, brain tumour, haematological cancers among others.
The anti-cancer therapeutics used are cytotoxic to not only tumour cells but also the normal cells. The anti-cancer property of curcumin is attributed to its ability to induce apoptosis in tumour cells without harming the healthy normal cells. Curcumin, apart from diferuloylmethane, contains minor fractions such as demethoxycurcumin (curcumin II), bisdemethoxycurcumin (curcumin III), and the recently identified cyclocurcumin. This suggests that its methoxy groups are essential for its anti-inflammatory and antiproliferative activity. Animal studies have shown, the anti-carcinogenic property of curcumin is due to its inhibition of tumour initiation and tumour promotion. Curcumin has been shown to suppress multiple signalling pathways and inhibit cell proliferation, invasion, metastasis, and angiogenesis.
Mechanism of cell death by curcumin:
Curcumin acts on a variety of molecular targets like transcription factors, growth factors and their receptors, cytokines, enzymes, and genes regulating cell proliferation, and apoptosis. It binds to about 33 proteins like thioredoxin reductase, cyclooxygenase-2, (COX2), protein kinase C, 5-lipoxygenase (5-LOX), and tubulin. Curcumin causes cell death by:
- Activation of cell death pathway
- Inhibition of growth/proliferation pathway
The following are a few of the Apoptotic and growth inhibitory pathways activated by curcumin:
- Caspase Activation
- Caspase-independent pathway
- Fas receptor aggregation
- Mitochondrial Activation
- Release of apoptosis-releasing factor
- Inhibition of growth factors and their receptors
- Direct DNA Damage
- Induction of DNA fragmentation
- Pro and anti-oxidant mechanism
Curcumin and Clinical Trials:
Phase I and phase Ⅱ clinical trials have already demonstrated the safety of curcumin even at high doses (8-12 g/d) over several months. Adverse events were mainly nausea and diarrhoea. Regardless of its excellent safety profile, the poor solubility and low bioavailability of curcumin are obstacles to therapeutic drug development. Data on the pharmacokinetics, metabolites, and systemic bioavailability of curcumin in rodents and humans show that curcumin is poorly absorbed, rapidly metabolized, and may have limited systemic bioavailability. Results from a phase Ⅰ clinical study of twenty-ﬁve patients with various pre-malignant or high-risk lesions suggested that oral curcumin may have chemo preventive effects on these lesions (histological improvement).
In another study from the Cleveland Clinic in Florida, five patients with familial adenomatous polyposis were treated with a combination of curcumin and quercetin three times a day for a mean duration of 6 months. The numbers and sizes of polyps were reduced in all patients compared to baseline values. Curcumin efficacy in the treatment of human pancreatic cancer has been reported in a phase Ⅱ clinical trial in patients with advanced disease. Bayet-Robert et al treated 14 advanced and metastatic breast cancer patients with a combination of curcumin and docetaxel. The study demonstrated that the combination therapy decreased the vascular endothelial grow factor (VEGF) levels and showed encouraging efficacy. Trials are also being conducted in Tata Memorial Centre, Mumbai to assess the application of curcumin in oral cancer and osteosarcoma.
To conclude, Curcumin has a crucial ability of selectively killing tumour cells without harming the healthy normal cells, gives impetus to further research into it. Research has been conducted in animal models as well as clinical trials, but there is always scope of research. Research needs to be done into the molecular targets mechanism in vivo as well as the efficacy profile.