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).