Phytochemical Therapy Regime Model System Mechanism of action Reference
Apigenin+5-Fluorouracil Apigenin+Cisplatin Chemotherapy Chemotherapy SCC25 SCC25 Synergistic effect, ↑Apoptosis, ↑iROS, ↑ TNF-R, ↑TRAIL-R, ↑Bcl-2, ↓Glutathione, induce cell cycle arrest in G2M phase. No synergistic effect, ┴ GLUT-1 & P AKT. (Chan et al., 2012) (Xu et al., 2014)
Betulinicacid+Radiation Radiation HNSCC: SCC9, SCC25 ┴cell survival, Act as radiosensitizer, ↓clonogenic survival. (Eder-Czembirek et al., 2010)
CAPE+5 Fluorouracil Chemotherapy TW2.6 ┴proliferation, Additive effect, ┴Akt (Kuo et al., 2015)
Curcumin+Radiation Curcumin+Cisplatin Curcumin+5FU/Doxorubicin/Cisplatin. Radiation Chemotherapy Chemotherapy SCC-1, SCC-9, In-vivo. CAL-27, UM- SCC1 NT8e. Radioenhancer, Additive effect, ┴growth, ↓COX2. Additive effect, ┴ IKKβ protein. Synergistic effect, ┴Growth, ↑apoptosis, ↓EGFR-ERK1. (Khafif et al., 2009) (Duarte et al., 2010) (Sivanantham et al., 2016)
EGCG+Luteolin EGCG+Erlotinib EGCG+Cisplatin Combination of phytochemi -cals Chemotherapy Chemotherapy Tu 212, Tu 686, 686 LN, 886 LN, In-vivo. HNSC CSCs (K3, K4, K5), In-vivo. Tu 686, Tu 212. Synergistic/additive effect, ┴growth, ↑apoptosis, ↓ki-67. ┴tumor growth, ↓Oct 4, ↓Sox-2, ↓Nanog, ↓CD44. ↑apoptosis, ┴phosphorylation of Bim. (Amin et al., 2010) (Lee et al., 2013) (Haque et al., 2015)
Honokiol+Paclitaxel Honokiol+Taxol Honokiol+ Cisplatin Honokiol+ Radiation Chemotherapy Chemotherapy Chemotherapy Radiation KB-8-5, KB-C1, KB-V1, KB-3-1, In-vivo. MDR SCCHN: KB-8-5, KB-V1 & KB-C1. SAS, OECM-1, GNM, SG. Tu212, Tu686, PCI-15A, JHU-022. Synergistic effect, ↑apoptosis, ┴growth, ↑caspase 3, ↑PARP, ↑cytochrome c, ↓Survivin, ↓EGFR-STAT3, ↓P-ERK, ↓P-Akt, ↓Ki67. ↓ P-glycoprotein, synergistic effect, arrest cell cycle, induce apoptosis, ┴PI3K/Akt/Mcl-1. ↓colony formation, ┴invasion, ┴migration, chemosensitizing effect with cisplatin, ↓ALDH1, ↓CD44, ↓IL-6, ↓P-STAT 3. ↓ Survivin, ↑cytotoxicity, ↑DNA damage, induce apoptosis. (Wang et al., 2014) (Wang et al., 2007). (Chang et al., 2018) (Wang et al., 2018).
BITC+Cisplatin Chemotherapy HN12, HN8, HN30 ↑apoptosis, ┴invasion, ┴migration, ↓viability, Sensitize cells to cisplatin, ┴EMT, ↓vimentin. (Wolf et al., 2014)
Sulforaphane+Radiation. Sulforaphane +PDT Radiation therapy Photodynamic therapy SCC-9, SCC-25, CAL-27, FaDu. AMC-HN3. Synergistic effect, Radiosensitizer, ↓proliferation, ↓clonogenic survival, ↓Akt, ↓Mcl-1. ↑apoptosis, ↑necrosis ↓viability, Synergistic effect, ↑ROS, ↑caspase3,8,9, ↑PARP (Kotowski et al., 2011) (Lee et al., 2015b)
Lupeol+Cisplatin Chemotherapy Tu 159, MDA1986, Hs677.Tg, CAL27, In-vivo. Synergistic effect, ↓metastasis, ↓NF-KB, ↓tumor volume. (Lee et al., 2007)
Luteolin+ Paclitaxel Chemotherapy SCC-4, In-vivo xenograft nude mice. Synergistic effect, ↑apoptosis ↓CDKs, ↓cyclins, ↓p-Rb, ↑Caspase 3,9, ↑cleaved PARP. (Yang et al., 2008)
Lycopene+Curcumin+ Radiation
Combination of phytochemi cal, & Radiation
PE/CA-PJ15
Synergistic effect with curcumin & Radiation, ↑apoptosis, ↓viability, ↓migration capacity.
(Camacho-Alonso et al., 2013)
Querceitin+Cisplatin Querceitin+Cisplatin Chemotherapy Chemotherapy Hep2 SCC25 (OSCC) Synergistic effect, ↑apoptosis, ↓Bcl-2 and ↓Bcl-XL, ↓Cu-Zn SOD, ↑ROS, ┴Akt/PKB phosphorylation. Additive effect, ↑apoptosis, ┴ p-Hsp-27, ↑p38 MAPK in DRSPs. (Sharma et al., 2005) (Chen et al., 2012b)
Resveratrol+Paclitaxel Resveratrol+Radiation Resveratrol+Etopside Resveratrol+Grape Seed Extract (GSE). Resveratrol+Taxol. Chemotherapy Radiation therapy Chemotherapy Combination of Phytochm -icals Chemotherapy CNE 2. FaDu, In-vivo. SCC25, CAL27 & FaDu. In-vivo: NQO induce tumoriogene -sis model. Hep-2 Synergistic effect, ↓HIF1-α, ↓mdr1, ↓MRP1. Synergistic effect, Radiosensitizing effects, ↓MVD in tumor, ┴tumor growth. Synergistic effect, ┴growth. ↑apoptosis, ↑autophagy, ↓proliferation, ↑AMPK-P, ↓p62. ┴proliferation, ↑apoptosis, ↑Bax, ↑PARP, ↑TRIB3, ↑Caspase 3, 8, ↓Bcl-2, ↓XIAP. (Quan et al., 2009) (Quan et al., 2014) (Heiduschka et al., 2014) (Shrotriya et al., 2015) (Lu et al., 2016)
SalB+ Celecoxib. Chemotherapy JHU-013, JHU-022, JHU-06, JHU-011. Antiproliferative, ↑apoptosis, ↓tumor growth. (Zhao et al., 2010)
Thymoquinone+ CDDP Thymoquinone+Cisplatin+Radiation Chemotherapy Combination of phytochem -icals & Radiation therapy UMSCC-14C, OEC. HNSCC: SCC25, CAL25 Synergistic effect, ↑apoptosis, ↑p53, ↑Caspase 9, ↓Bcl-2. ┴proliferation, ┴clonogenic survivial, Radiosensitizer, Synergistic effect with radiation. (Alaufi et al., 2017) (Kotowski et al., 2017)