TABLE 9.
Chemotherapeutic and Chemopreventive phytochemicals/Herbal derivative with anti-cancer and anti-HPV activity in HNC.
| Phytochemicals/ Herbal Products; PubChem-CID (Class) | Cell type/Model/Clinical | Stage of Cancer | Anti-cancer activity in HPV positive cell | HPV specific effect | Ref. |
|---|---|---|---|---|---|
| EGCG (Green Tea Polyphenol (-)-Epigallocatechin-3-gallate) | In vitro study: YCU-N861 a (NPSCC) and YCU-H891# (Hypopharyngeal SCC) | Promotion | • G1 phase Cells ↑; Cyclin D1 ↓, pRB ↓ | NA | Masuda et al. (2001) |
| • Apoptosis ↑; Bcl2 ↓, Bax ↑, Caspace 9↑: apoptosis↑. | |||||
| CID: 65064 | • Phosphorylation of EGFR, STAT3, ERK proteins ↓ | ||||
| • Basal and transforming growth factor α-stimulated C-fos and Cyclin D1 promoter activity ↓ | |||||
| Emodin (Polygonum multiflorum) | In vitro study: CNE-1# (NPSCC epithelioid cell line) | Promotion and progression | • ROS ↑; Oxidative damage ↑ | NA | Hou et al. (2013) |
| • Apoptosis ↑ | |||||
| CID: 3220 (Trihydroxyanthraquinone) | • HIF-1α ↓ | ||||
| • Promotion of survival ↓ | |||||
| Curcumin | In vitro study: 93VU147T a (OSCC) | Promotion and progression | • Cell viability ↓ | • HPV16/E6 mRNA ↓ | Mishra et al. (2015) |
| CID: 969516 (Phytopolylphenol) | • Bcl-2 ↓, cIAP2 ↓, Bax ↑ | • E6-mediated p53↓ | |||
| • AP-1 ↓, NF-KB ↓ | |||||
| CIP-36 (Novel podophyllotoxin derivative) | In-vitro study: KB a (HeLa contaminant epidermal carcinoma of mouth) | Promotion and Progression | • Cell proliferation ↓ | NA | Cao et al. (2015) |
| • Blocks cells in S/G2+M phase | |||||
| • Effects DNA cleavage mediated by Human Topo IIα | |||||
| Sulforaphan | In-vitro study: UM-SCC-22A (Hypopharyngeal SCC), UM-SCC-1 (OSCC), CAL33 (Tongue OSCC), and UPCI: SCC090 a (Tongue OSCC). | Initiation, promotion and progression | • NRF2 signaling ↑ | NA | Bauman et al. (2016) |
| CID: 5350 (Isothiocyanate | In-vivo study: Female C57BL/6 mice (5–6 weeks; 18 mice/group). | • STAT3 phosphorylation ↓ | |||
| Clinical study: 10 human subjects | • Promotes cell death | ||||
| • Consumption of BSE (Broccoli sprout extracts rich in sulforaphane) beverage demonstrated NRF2 pathway activation in oral mucosa. | |||||
| 6-Gingerol | In-vitro study: KB a (HeLa contaminant epidermal carcinoma of mouth), SCC4 (Tongue SCC). | Promotion and progression | • Tumor cell proliferation ↓ | NA | Kapoor et al. (2016) |
| CID: 442793 (Beta-hydroxy ketone) | |||||
| • Cytotoxicity ↑ | |||||
| • Caspase-3 pro-apoptotic activity ↑ | |||||
| • Sub-G1 cells ↑; G2 and S phase arrest | |||||
| Curcumin | In-vitro study: UD-SCC-2 a (Hypopharyngeal SCC); UPCI:SCC131 (OSCC), UPCI:SCC84 (OSCC) | Promotion, Proliferation and progression | • Cell growth↓ | • HPV 16 E6/E7 ↓ | Bano et al. (2018) |
| CID: 969516 (Phytopolylphenol) | • Orosphere formation ability↓ | • miRNA21 ↓ | |||
| • Cytotoxic effect | |||||
| Thymol | In-vitro study: CAL27 (Tongue OSCC), SCC4 (Tongue OOS), SCC9 (Tongue OSCC) | Initiation, promotion and progression | • Cellular proliferation↓; Apoptosis↑ | NA | De La Chapa et al. (2018) |
| CID: 6989 (Monoterpene) | • Long lasting cytotoxic effects | ||||
| In-vivo study: athymic nude mice, Cal27- and HeLa-derived a mouse xenografts. | • Long lasting cytotoxic effects | ||||
| • TRPA1 activation | |||||
| • Mitochondrial membrane potential↓ | |||||
| • Mitochondrial dysfunction | |||||
| • In vivo Tumor growth↓ | |||||
| Apigenin (40 ,5,7, -trihydroxyflavone, AP) | In-vitro study: SHEE a , b (Human esophageal epithelial cell line) | Promotion and progression | • Migration Ability↓ | NA | Yin et al. (2020) |
| • G1 phase arrest; CDK4↓, Cyclin-D1↓, pRB↓ | |||||
| • Apoptosis↑ activation of caspase-3. | |||||
| • DNA Alkylation↓ |
HPV16/18 positive cell lines NA: No HPV-specific effects have been reported.
Some research papers have classified Human esophageal carcinoma under Head and neck squamous cell carcinoma but it should be classified under the broader category of digestive system carcinoma.
Abbreviations: AP-1: Activator protein 1; Bax: Bcl-2-associated X protein; Bcl2: B-cell lymphoma 2; BSE: Broccoli Sprot extracts; CDK: Cyclin-dependent kinases; cIAP: Calf Intestinal Alkaline phosphatase; EGFR: Epidermal growth factor receptor; ERK: Extracellular-signal-regulated kinase; HIF-1α: Hypoxia-inducible factor 1-alpha; HPV: Human papillomavirus; IFN-γ: Interferon gamma; NF-Kβ: Nuclear factor kappa light chain enhancer of activated B cells; NRF2: Nuclear factor erythroid 2-related factor 2; pRB: phosphorylated Retinoblastoma; STAT3: Signal transducer and activator of transcription 3; Topo IIα: topoisomerase II- alpha; TRPA1: Transient receptor potential cation channel, subfamily A, member 1.