Anticancer effects of CH based on in vitro studies
Type of cancer | Study model | Effects | Mechanisms | Concentration | References |
---|---|---|---|---|---|
Melanoma | SK-ML-28, MelC and B16F10 | Anti-proliferative, inhibits angiogenesis | ↓ Cancer cell proliferation, ↑ arrest in the G2/M phase, ↓ cell numbers in the G0/G1 phase, ↑ tetraploid cells, ↑ DNA damages, ↑ γ-histone 2AX (γH2AX), ↓ ataxia telangiectasia and Rad3-related (ATR), ↑ p-check point kinase1 (Chk1), ↑ p-ataxia-telangiectasia mutated (ATM), ↑ p-p53 (Ser15), ↓ vascular endothelial growth factor (VEGF), ↓ VEGF-receptor 2 (VEGFR2), ↓ hypoxia-inducible factor-1 alpha (HIF-1α), ↓ HIF-1β, ↓ p-signal transducer and activator of transcription 3 (STAT3, pY705), ↑ ROS | 0 µmol, 20 µmol, 40 µmol, and 80 µmol | [12] |
A375SM and A375P | Induces apoptosis and autophagy | ↓ Viability of cancer cells, ↑ nuclear and chromatin condensation, ↑ Bcl-2-associated X (Bax), ↑ c-polyadenosine-diphosphate-ribose polymerase (PARP), ↓ Bcl-2, ↑ light chain 3 (LC3), ↑ beclin 1, ↑ autophagic vacuoles, ↑ acidic vesicular organelles, ↓ p-mTOR, ↓ p-70-kDa ribosomal protein S6 kinase (P70S6K), ↓ p-S6K, ↓ p-eIF4E-binding protein (4EBP1) | 0 µmol, 20 µmol, 40 µmol, 60 µmol, 80 µmol and 100 µmol | [13] | |
B16F10, RAW264.7, DC2.4 | Improve tumor immune response | ↓ Cancer cell viability, ↑ major histocompatibility complex I (MHCI), ↑ interleukin-12 (IL-12), ↓ IL-10, ↑ STAT4, ↑ interferon-γ (IFN-γ), ↑ tumor necrosis factor-ɑ (TNF-ɑ) | - | [14] | |
Myeloid | Myeloid-derived suppressor cells (MDSCs), granulocytic MDSC (G-MDSC), and monocytic MDSC (M-MDSC) | Induces apoptosis | ↑ G0/G1 cell cycle arrest, ↓ proliferation of MDSCs, ↓ arginine-1 (Arg-1), ↓ cyclooxygenase-2 (COX-2), ↓ inducible nitric oxide synthase (iNOS), ↓ nitric oxide (NO), ↑ p-Akt | 10 µmol (low dose) and 20 µmol | [15] |
Leukemia | U937 | Induces apoptosis | ↑ Bax, ↓ Bcl-2, ↑ caspase-3, ↑ phospholipase C-1 degradation, ↓ X-linked inhibitor of apoptosis protein (XIAP), ↓ Akt | - | [16] |
Mucoepidermoid | MC-3 | Induces apoptosis and autophagy | ↓ Cancer cell viability, ↑ nuclear condensation and shrinkage, ↑ apoptotic bodies, ↑ c-PARP, ↑ Bax, ↓ Bcl-2, ↑ LC3-II, ↑ beclin 1, ↓ sequestosome 1 (p62), ↓ p-mTOR, ↓ p-extracellular signal-regulated kinases 1/2 (ERK1/2), ↑ p-Jun N-terminal kinase (JNK), ↑ p-p38 | 0 µmol, 50 µmol, and 100 µmol | [17] |
Nasopharyngeal carcinoma | CNE1 | Induces apoptosis | ↑ Cancer cell death, ↑ sub-G1 population, ↑ cell shrinkage, ↑ chromatin condensation, ↑c-PARP cleavage, ↑ c-caspase 8 | 10 µmol, 20 µmol, and 40 µmol | [18] |
Brest cancer | MDA-MB-231 | Induces apoptosis | ↓ HIF-1α, ↑ Bax, ↑ p53, ↓ Bcl-2, ↓ cyclin D1, ↓ p-STAT3 | CH and radiotherapy, combination index (CI) of 0.495 | [19] |
T47D | Induces apoptosis | ↑ Cytotoxicity towards cancer cell, ↓ hTERT gene | Artemisinin and CH encapsulated poly(lactic-co-glycolic acid) (PLGA)-poly(ethylene glycol) (PEG) nanoparticles (NPs), IC50 = 12.51 μM | [20] | |
Breast and BT474 | Induces apoptosis and anti-proliferative | ↑ Destabilization of the genome, ↓ cancer cell survival, ↑ γH2AX, ↑ PKcs-pS2056, ↓ p53-binding protein 1 (53BP1), ↓ RAD51 | 0 µmol, 5 µmol, 10 µmol, 15 µmol, 20 µmol, and 30 µmol | [21] | |
MDA-MB-231 and MDA-MB-231_luc cells | Inhibits metastasis | ↓ Cancer cell viability, ↓ PI3K, ↓ NF-κB, ↓ matrix metalloproteinases-10 (MMP-10), ↓ MMP-2 | 0–100 µmol | [22] | |
MDA-MB-231 | Anti-proliferative and induces apoptosis | ↑ Cytotoxicity towards cancer cell, ↑ cell accumulation in G2/M phase, ↑ apoptosis frequency, ↑ microRNA-132 (miR-132), ↑ miR-502c, ↓ HN1 and P65 | Curcumin and CH encapsulated PLGA-PEG NPs, combination index (CI50) = 0.47 | [23] | |
MCF7 | Induces apoptosis | ↓ Cancer cell viability, ↑ apoptosis frequency, ↑ apoptotic cell bodies | 5 mmol/L, 10 mmol/L, 20 mmol/L, and 30 mmol/L | [24] | |
Lung | A549 | Induces apoptosis | ↓ Cancer cell viability, ↑ caspase-3 and caspase-9, ↑ Bax/Bcl-2 artio, ↑ Bax, ↓ Bcl-2 | IC50 = 49.2 (48 h) and 38.7 (72 h) | [25] |
Gastric | AGS | Inhibits metastasis | ↓ Endogenous and inducible receptor originated from nantes (RON) expression, ↓ growth response-1 (Egr-1), ↓ NF-κB, ↓ phorbol-12-myristate-13-acetate-(PMA) | 0–100 µmol | [26] |
AGS | miRNA related | ↑ Cytotoxic towards cancer cell line, ↑ miR-9, ↑ Let7-a, ↓ miR-18a, ↓ miR-21, ↓ miR-221 | PLGA-PEG encapsulated CH (0–160 µmol) | [27] | |
Hepatoma | HepG2 | Induces apoptosis | ↑ Cancer cell death, ↑ sub-G1 population, ↑ cell shrinkage, ↑ chromatin condensation, ↑ c-PARP cleavage, ↑ c-caspase 8 | 10 µmol, 20 µmol, and 40 µmol | [18] |
Pancreatic | MIA PaCa-2 | Induces apoptosis | ↓ Cancer cell viability, ↑ caspase-3, ↑ c-PARP, ↑ G protein-coupled estrogen receptor, ↑ G2/M phase cells, ↓ ERα, ↓ c-Myc | 0–100 µmol | [28] |
Colorectal | SW48, SW480, SW620, HT-29 and HCT-116 | Induces autophagy | ↓ Cancer cell viability, ↑ LC3II, ↓ p-mTOR, ↑ p-adenosine monophosphate-activated protein kinase (AMPK), ↓ p-Akt, ↑ ROS production | 0 µmol, 20 µmol and 50 µmol | [29] |
HCT-116 | Induces apoptosis | ↑ Cancer cell death, ↑ sub-G1 population, ↑ cell shrinkage, ↑ chromatin condensation, ↑ c-PARP cleavage, ↑ c-caspase 8 | 10 µmol, 20 µmol, and 40 µmol | [18] | |
Prostate | PC-3 | Induces apoptosis | ↓ Vasculogenic mimicry (hypoxia-induced) ↓ HIF-1α, ↓ vascular endothelial-cadherin (VE-cadherin), ↓ VEGF, ↓ Bcl-2, ↑ c-PARP, ↑ caspase-3, ↓ sphingosine kinase-1 (SPHK-1), ↓ p-Akt, ↓ p-glycogen synthase kinase 3β (GSK-3β) | 10 µmol | [30] |
PC-3 | Induces apoptosis | ↓ Cancer cell viability, ↑ cell shrinkage, ↑ apoptosis frequency | 10 µmol, 20 µmol, 30 µmol, and 40 µmol | [31] | |
Endometrial | HEC1Aand Ishikawa | Induces autophagy and apoptosis | ↓ Proliferation and colony formation activity, ↑ apoptotic cells, ↑ Bax, ↓ Bcl-2, ↑ LC3II, ↑ Beclin 1, ↓ p62, ↑ ROS accumulation, ↓ pAkt, ↓ pmTOR | 0 µmol, 10 µmol, 20 µmol, 40 µmol, and 80 µmol | [32] |
Cervix | Hela | Induces apoptosis | ↑ Cancer cell death, ↑ sub-G1 population, ↑ cell shrinkage, ↑ chromatin condensation, ↑ c-PARP cleavage, ↑ c-caspase 8 | 10 µmol, 20 µmol, and 40 µmol | [18] |
↑: over expression; ↓: down expression; -: blank