Table 2.

Conducted investigations on the treatment of cervical cancer with curcumin

Type of curcumin	Dose	Main target (s)	Main effect (s)	Model (in vivo/in vitro/human)	Cell line	Ref
Curcumin	20 μM for 72h	N-cadherin, Vimentin, Slug, PIR, Pirin	Inhibition of cancer cell growth, migration, invasion Inhibition of angiogenesis Induction of apoptosis and necrosis Induction of cell cycle arrest Increased radiosensitization of cancer cells	In vitro	SiHa	[63]
	2.5, 5 μmol/L In vivo (150-200 μL)	Notch-1, NF-κB, VEGF		In vivo In vitro	Me180	[57]
	5× IC50 (34.23 μM/ml)	Wnt/β-catenin NF-kB pathway		In vitro	HeLa	[64]
	13 μM	BRCA1, p-p53, p-H2A.XSer140		In vitro	HeLa	[59]
	IC50= 16.52 μM	ROS, p21, Bax, p53, ROS, p21, Bax		In vitro	HeLa	[65]
	10 μM In vivo (4 mg/kg)	-		In vitro In vivo	HeLa	[66]
	10 μM	TGF-β activates Wnt/β-catenin signaling pathway		In vitro	SiHa HeLa	[67]
	10 μM	NF-κB-p53-caspase-3 pathway	Curcumin improves the paclitaxel-induced apoptosis of cervical cancer cell lines infected with HPV.	In vitro	CaSki HeLa	[68]
	5 μM	-	Curcumin-induced apoptosis and oxidative stress	In vitro	HeLa	[69]
	1000 and 1500 mg/kg for 30 days	-	Curcumin inhibits angiogenesis and tumor growth mediated by decreasing the expression of VEGF, EGFR, and COX-2.	In vivo	-	[62]
	50 μM	-	Curcumin sensitizes cervical cancer cells to cisplatin-based chemotherapy through inhibition of Pgp1and MRP1.	In vitro	SiHa SiHaR	[70]
	20 μM	-	Curcumin induced ER stress-mediated apoptosis via increasing of ROS generation and by activation of CHOP	In vitro	C33A CaSki HeLa ME180	[61]
	IC50: 17 μM (HeLa), 12 μM (ME-180), 51 μM (SiHa), 21 μM (SW756) Dose: 50 μM for 48h	-	Curcumin-based vaginal cream effectively eradicates HPV positive cervical cancer cells.	In vitro	HeLa ME-180 SiHa SW756	[71]
	10 and 25 μM	Akt, MAPK, and AP-1 pathways	Curcumin potentiates the antitumor effects of paclitaxel by downregulating Akt, MAPK, and AP-1 pathways and decreasing the transcription of NF-kB target genes.	In vivo	-	[72]
	25 and 50 μM	-	Curcumin can induce apoptosis by inhibition of PCNA, Cyclin D1, telomerase, and p16 and by activation of p53 and p73 in HPV-negative cancer cells pretreated with estradiol.	In vivo	HeLa SiHa CaSki C33A	[54]
	50 and 100 μM for 24h	Apoptosis and inflammatory pathways	Curcumin mediates apoptosis in SiHa and HeLa cell lines. Curcumin can act as an anti-proliferative and anti-inflammatory agent for Ca Ski, HeLa, and SiHa cells	In vitro	HeLa SiHa CaSki	[73]
	15 μM for 48h	-	Curcumin exhibits antitumor activity against cervical cancer cells. Curcumin downregulates PGE2 expression.	In vitro	HeLa	[56]
	10 μM for 8h	MAP kinase pathway	Curcumin is a potent radiosensitizer by increasing ROS production and overacts the MAP kinase pathway.	In vitro	HeLa SiHa	[74]
	10μMCombined curcumin (10μM) ultrasound (8 s of 5-7.5 MHz)	-	Curcumin can lead to necrosis in cervical cancer cell lines. Combined curcumin ultrasound enhances necrosis in cervical cancer cell lines.	In vitro	HeLa SiHa C33A	[60]
ST06-AgNPs	IC50: 1μM Dose: 1-2 μM Dose: 5 mg/kg body weight for 30 days (In vivo)	-	Inhibited cancer cell growth	In vivo In vitro	HeLa	[75]
Folic acid-modified liposomal curcumin	IC50: 1.47 μg/mL for free curcumin IC50: 0.45 μg/mL for (DSPE)-PEG2000-FA-LPs/CUR Dose: 25 mg/kg for 51 days (In vivo)	-	Anti-proliferative effects	In vitro In vivo	HeLa	[76]
4-Bromo-4'-chloro pyrazoline	IC50: 8.7μg/ml for Chloro bromo analogIC50: 42.24 μg/mL for curcumin	-	Apoptosis induction	In vitro	HeLa	[77]
Chloro and bromo-pyrazolecurcumin	IC50: 14.2 and 18.6 μg/ml for Chloro derivative and bromo analog, respectively. IC50: 42.4 μg/ml for curcumin	-	Apoptosis induction	In vitro	HeLa	[78]
Curcumin-loaded microbubble	1.25–40 μM	-	Decreased cancer cell viability	In vitro	HeLa	[79]
Bisdemethoxycurcumin	5μM for 24 and 48h	NF-kB, MMP-2 and -9 Pathways	Anti-migration and anti-invasion effects	In vitro	HeLa	[80]
Curcumin-PDT	-	Notch signaling pathway	Necrosis induction	In vivo	Me180	[81]
Curcumin-loaded micells	50 μg/mL	-	Increased cytotoxicity against cancer cells Apoptosis induction	In vitro	HeLa HepG2 NIH-3T3	[82]
Demethoxycurcumin	15 μM IC20: 7.5 μM	NF-κB Pathways	Anti-migration and anti-invasion effects	In vitro	HeLa	[83]
Curcumin-loaded chitosan nanoparticles	24μM	-	Apoptosis induction Anti-proliferative effects Showed better chemopreventive and chemotherapeutic effects than curcumin	In vitro	SiHa	[84]
Difluorinated curcumin Folate decorated bovine serum albumin (FA-BSA) nanoparticles loaded with Difluorinated curcumin (CDF) (FA-BSA-CDF)	Dose: 2 μM (Difluorinated curcumin and FA-BSA-CDF) Dose: 0.5 μM (Combination)	-	Synergistic anticancer effectsApoptosis induction	In vitro	HeLa SKOV3	[85]
Curcumin-nanoemulsion	20 to 40μM	-	Apoptosis induction	In vitro	CasKi SiHa HaCaT	[86]
Curcumin-Loaded TPGS/F127/P123 Mixed Polymeric Micelles	Dose: 8 μg/mL Dose: 25 mg/kg for 11 times in 2 days (In vivo)	-	Increased cytotoxicity against cancer cells Induction of apoptosis and cell cycle arrest	In vivo In vitro	HeLa NIH3T3 cells	[87]
Curcumin-loaded chitosan-alginate-sodium tripolyphosphate nanoparticles	50 μg/mL	Bax , Bcl-2	Anti-proliferative effects Apoptosis induction	In vitro	HeLa	[88]
Folic acid conjugated polymeric micelles loaded with a curcumindifluorinated	0.47 ± 0.14 μM	PTEN, NF-κB	Apoptosis induction	In vitro	HeLa	[89]
Curcumin-loaded chitosan Nanoparticles	108 μM	Bax, Bcl-2	Apoptosis induction	In vitro	SiHa Hela Caski C33a	[90]
Tetrahydrocurcumin	100, 300, or 500 mg/kg body weight for 30 days	COX-2, EGFR, p-ERK1&2, p-AKT, Ki-67	Apoptosis induction Antitumor Effect	In vivo	CaSki	[91]
Nano-Curcumin	20 and 25 μM for 48h	Anti-survival pathways	Inhibited cancer cell growth Induction of apoptosis and cycle cell arrest	In vitro	SiHa, Caski	[19]
Tetrahydrocurcumin	50, 100 mg/kg	-	Inhibited cancer cell growth Anti-angiogenesis effects	In vivo In vitro	CaSki	[92, 93]
Curcumin (CCM)-loaded nanoscale zeolitic imidazolate framework-8 (CCM@NZIF-8) nanoparticles	Dose: 1-10 μg/mL Dose: 2.5 mg/kg body weight for 6 times in 2 days (In vivo)	-	Anti-proliferative effects Showed higher efficacy than free curcumin	In vivo In vitro	HeLa	[94]
Curcumin-loaded cationic liposome	IC50: 16, 21 μM	-	Apoptosis induction	In vitro	HeLa SiHa	[95]