Table 1.

List of included studies and their main characteristics

Name of the researcher	Year of the study	In-vitro/In-vivo	Place	Sample size	Assay	Cell lines	Duration	Dosage	Conclusion of the study
Gabriel Alvares Borges et al.[23]	2018	In-vitro	India	3	1. Western blotting 2. MTT assay 3. Sphere formation assay 4. QRT-PCR	1. HPV16 positive OSCC cell line-1 2. HPV16 negative OSCC cell line-2	24 hours—cell proliferation and QRT-PCR 7-10 days-sphere formation	0-50 µM	Downregulation of miR-21 expression on treating with curcumin is seen in both HPV positive and HPV negative oral cancer cell lines but higher effects are seen in HPV positive cancer cell lines and curcumin also inhibits cell growth in oral cancer cells (in-vitro)
Ji Young Kim et al.[7]	2012	In-vitro	South Korea	1	1. Cell viability assay 2. Apoptosis assay 3. ROS measurement 4. Western blot analysis	OSCC cell line (YD1OB)	24 hours	10-40 µM	Curcumin activates autophagy in oral squamous cell carcinoma and it is activated by curcumin induced ROS production. Curcumin also accelerates apoptotic molecules in oral squamous cell carcinoma.
Shengkai Liao et al.[8]	2011	In-vitro	China	1	1. Colonogenic assay 2. Real time RT PCR 3. Annexin V assay 4. Western blot 5. Invasion assay 6. ELISA 7. Flow cytometry 8. Luciferase assay	Human OSCC cell line	24, 48, and 72 hours	2.5, 5.0, 7.5 µM	Curcumin induce apoptosis, inhibits cell growth, downregulates NOTCH-1 pathway which in turn leads to downregulation of BCL-2, MMP9, VEGF and cyclin D in oral squamous carcinoma cell lines.
Alok Mishra et al.[9]	2015	In-vitro	India	1	1. MTT assay 2. PCR 3. Northern blot 4. Electrophoretic mobility shift assay	Human oropharyngeal squamous cell cancer cell lines	24, 48, 72 h	0-100 µM	Curcumin downregulates HPV transcription ( NF-κB and AP-1) in HPV positive oral cancer cell lines. Curcumin also inhibits transcription of E6 oncogene in HPV positive oral cancer cell lines
Can Xiao et al.[10]	2014	In-vitro	China	1	1. MTT assay 2. qRT-PCR 3. colony formation assay 4. Western blot	Human tongue squamous cancer cell lines	72 h.	20, 40, 60 µM	Curcumin induces the expression of miR-9 that mediates the inhibition of SSC9 cells proliferation and Wnt/βcatenin signaling pathway in human tongue squamous cell cancer cell lines
Yu-Chuan Lin et al.[11]	2010	In-vitro	Taiwan	1	1. Cell cycle analysis 2. Flow cytometry	Human oral SAS cell lines	24 h	0-30 µM	The inhibition effects of curcumin on the growth of human oral squamous carcinoma in vitro were significant.
Chao Ma et al.[12]	2020	In-vitro	China	1	1. Cell proliferation assay 2. Cell migration assay 3. TUNEL assay 4. Flow cytometry 5. Western blot	Human tongue cancer cell lines	24 h	0-100 µM	Curcumin inhibits cell proliferation, cell migration, apoptosis, and induces S phase cell cycle arrest in tongue cancer cell lines. Curcumin can be effectively used in treating oral cancers.
Charlotte Kötting et al.[13]	2021	In-vitro	Germany	1	1. Annexin V/apoptosis assay	HNSCC cell lines	48 h.	5, 10, and	Curcumin is a potent NF-κB inhibitor that
					2. Western blot 3. Flow cytometry 4. ELISA 5. RT q- PCR 6. Migration assay 7. NF-κB ELISA			20 µM	is able to reverse the process of EMT back to MET, reducing Treg-attracting chemokine CCL22, with visible inhibition of Treg migration.
Tian Liu et al.[14]	2021	In-vitro	China	2	1. Colony formation assay 2. Western blot 3. RT q-PCR 4. Cell transfection 5. Dual luciferase	HSC 3 and CAL 33 cell lines	24-48 h.	5-20 µM	Inhibits the proliferation and NF-κB activity of OSCC cells and also decreases the expression of f Sp1, p65 and HSF1 in OSCC cells
Feng Liao et al.[15]	2018	In-vitro	China	1	1. MTT assay 2. Western blot 3. IHC 4. Immunofluorescence 5. Flow cytometry	CAD 27 and Fadu cell lines	-	-	On treating with curcumin reduction in cell proliferation and growth was seen. And also decreased the expression of PDL1 and p-STA was seen in CAD 27 and fadu cell lines
Yuichi Ohnish et al.[17]	2020	In-vitro	Japan	2	1. Scratch wound healing cell migration assay 2. Matrigel cell invasion assay 3. Western blot	The human tongue-derived OSCC cell line HSC-4 and Ca9-22	2 h scratch wound healing cell 48 h-matrigel cell invasion assay	15 µM	Pre- treatment with Curcumin results in reduced cell invasion in hepatocyte growth factor (HGF) induced HSC-4 cell lines. And also, it reduces Epithelial mesenchymal transition in both HGF induced HSC-4 and Ca9-22 cell lines by repressing c-Met and ERK activation.
Ardito F et al.[16]	2018	In-vitro	Italy	1	1. MTT assay 2. Migration assay 3. Apoptosis assasssy	TSCC cell lines	24, 48, 72 h	0, 5, 10, 20, 50 µM	Reduction in cell proliferation, apoptosis and migration was seen on treating with curcumin at different time and concentration.
Lei Zhen et al.[21]	2014	In-vitro	China	1	1. Cell proliferation assay 2. Cell cycle analysis 3. Transwell cell Matrigel invasion assay 4.Real time PCR 5.Western blot	SCC-25 cell lines	24, 48 h