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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]