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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
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
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
20 μM - Curcumin induced ER stress-mediated apoptosis via increasing of ROS generation and by activation of CHOP In vitro C33A
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
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
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
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
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
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
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
Dose: 2 μM (Difluorinated curcumin and FA-BSA-CDF)
Dose: 0.5 μM (Combination)
- Synergistic anticancer effectsApoptosis induction In vitro HeLa
Curcumin-nanoemulsion 20 to 40μM - Apoptosis induction In vitro CasKi
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
NIH3T3 cells
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
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,
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