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Table 2 Conducted investigations on the treatment of cervical cancer with curcumin

From: Therapeutic role of curcumin and its novel formulations in gynecological cancers

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]