2.3 Combinatorial effect of different Phytochemical on HNC
Curcumin given in combination with Resveratrol was found to be more productive in inhibiting the growth of tumor in in-vivo and as well as in in-vitro cancer cell growth in HNC as compared to curcumin given alone. Combination treatment increased the Bax/Bcl-2 ratio, PARP-1 cleavage, inhibited the ERK1 and ERK2 phosphorylation It also induced cytoplasmic NF-κB accumulation which results in reducing the growth of transplanted Salivary gland cancer cells [SALTO] more effectively than curcumin alone (Masuelli et al. , 2012).
Genistein shows synergistic effects with other isoflavones, such as biochanin A (Johnson et al. , 2010b) and quercetin in oral cancer (Browning et al. , 2005); (Walle et al. , 2005).
EGCG showed synergistic effect with EGFR-TKI erlotinib in HNC cell lines derived from tumor sample Tu212 and Tu686.Combination treatment induced apoptosis in HNC cells via regulating Bcl-2 and Bim post-transcriptionally (Haque et al. , 2015). EGCG, curcumin and resveratrol combination inhibited tumorigenicity in HNC significantly (Piao et al. , 2016). Synergistic effect of Lycopene, Curcumin and radiation were also observed (Camacho-Alonso et al. , 2013). Lycopene increased the cytotoxic activity in the human oral squamous cell carcinoma (OSCC) PE/CA-PJ15 cell line & also reduced migration capacity of cells, while combinationatoiral effect of lycopene or curcumin with radiation showed synergic effect (Camacho-Alonso et al. , 2013). Similarly Resveratrol along with Curcumin was more potent in inhibiting the growth of HNSCC in-vitro and in-vivopreclinical models than curcumin alone (Masuelli et al. , 2014). Resveratrol synergistically enhanced the effects of etoposide in HNSCC cell lines (Heiduschka et al. , 2014)
Resveratrol and grape seed extract (GSE) decreased the incidence as well as prevented the severity and multiplicity of 4NQO-induced preneoplastic & neoplastic lesions. Both these phytochemicals increased the activation of metabolic regulator phospho-AMPK [Thr172] & also downregulated the p62 [autophagy flux marker], thus inhibiting proliferation through modulation of AMPK activation, and inducing apoptosis and autophagy (Shrotriya et al. , 2015).
Synergistic effect of Sulforaphane with photodynamic therapy (PDT) was also reported, Combination treatment of both SFN and PDT significantly decreased the cell viability via increasing the ROS and extent of necrosis and caspase-mediated apoptosis (Lee et al. , 2015b).