Colorectal cancer is one of the commonest cancers in the world and it is also a common cause of cancer-related death worldwide. Despite advanced treatment strategies, the disease is rarely cured completely due to recurrence. Evidence shows that this is due to a small population of cells, called cancer stem cells (CSCs), in the tumour mass that have the self-renewal and differentiation potential to give rise to a new tumour population. Many pre-clinical and clinical studies have used curcumin and its analogues as anti-cancer agents in various types of cancer, including colorectal cancer. Intriguingly, curcumin and its analogues have also recently been shown to be effective in lowering tumour recurrence by targeting the CSC population, hence inhibiting tumour growth. In this review, we highlight the efficacy of curcumin and its analogues in targeting colorectal CSC and also the underlying molecular mechanism involved. Curcumin, in the presence or absence of other anti-cancer agents, has been shown to reduce the size of tumour mass and growth in both in vivo and in vitro studies by affecting many intracellular events that are associated with cancer progression and CSC formation. An insight into the molecular mechanism has unraveled the mode of action via which curcumin could affect the key regulators in CSC, importantly; (1) the signaling pathways, including Wnt/β-catenin, Sonic Hedgehog, Notch and PI3K/Akt/mTOR, (2) microRNA and (3) the epithelial-mesenchymal transition at multiple levels. Therefore, curcumin could play a role as chemosensitiser whereby the colorectal CSCs are now sensitised towards the anti-cancer therapy, therefore, combination therapy using anti-cancer agent with curcumin could be much more effective than treatment using a single cancer agent. This potential treatment modality can be further developed by employing an effective delivery system using a nanotechnology based approach to treat colorectal cancer.

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The combination of two silent mutations, c.1311C>T in exon 11 and IVS11 T93C (glucose-6-phosphate dehydrogenase (G6PD) 1311T/93C), with unknown mechanism, have been reported in G6PD-deficient individuals in Asian populations including Malaysian aboriginal group, Negrito. Here, we report the screening of G6PD gene in 103 Negrito volunteers using denaturing high-performance liquid chromatography (dHPLC) and direct sequencing. A total of 48 individuals (46.6%) were G6PD deficient, 83.3% of these carried G6PD 1311T/93C with enzyme activity ranging from 1.8 to 4.8 U gHb(-1). Three novel single-nucleotide polymorphisms (SNPs), rs112950723, rs111485003 and rs1050757, were found in the G6PD 3'-untranslated region (UTR). Strong association was observed between haplotype 1311T/93C and rs1050757G, which is located inside the 35 bp AG-rich region. In silico analysis revealed that the transition of A to G at position rs1050757 makes significant changes in the G6PD mRNA secondary structure. Moreover, putative micro (mi)RNA target sites were identified in 3'-UTR of G6PD gene, two of these in the region encompassing rs1050757. It could be speculated that rs1050757 have a potential functional effect on the downregulation of mRNA and consequently G6PD deficiency either by affecting mRNA stability and translation or mirRNA regulation process. This is the first report of biochemical association of an SNP in 3'-UTR of G6PD gene and the possible role of mRNA secondary structure.

The presence of the risk allele (G) of FTO rs9930506 was not associated with an increased risk of obesity. Malaysian Indians had a significantly higher frequency of the risk allele (G). Indian participants expressed higher atherogenic phenotypes compared to Chinese and Malays. FTO rs9930506 may interact with dietary protein and vitamin E and modulate hsCRP levels.

This study aims to define the prevalence and the molecular basis of G6PD deficiency in the Negrito tribe of the Malaysian Orang Asli. Four hundred and eighty seven consenting Negrito volunteers were screened for G6PD deficiency through the use of a fluorescent spot test. DNA from deficient individuals underwent PCR-RFLP analysis using thirteen recognized G6PD mutations. In the instances when the mutation could not be identified by PCR-RFLP, the entire coding region of the G6PD gene was subjected to DNA sequencing. In total, 9% (44/486) of the sample were found to be G6PD-deficient. However, only 25 samples were subjected to PCR-RFLP and DNA sequencing. Of these, three were found to carry Viangchan, one Coimbra and 16, a combination of C1311T in exon 11 and IVS11 T93C. Mutation(s) for the five remaining samples are unknown. The mean G6PD enzyme activity ranged 5.7 IU/gHb in deficient individuals. Our results demonstrate that the frequency of G6PD deficiency is higher among the Negrito Orang Asli than other Malaysian races. The dual presence of C1311T and IVS11 T93C in 64% of the deficient individuals (16/44) could well be a result of genetic drift within this isolated group.