|
| Cancer type | Cancer cells | Extracts (plant parts, solvents, further fractionation) | Biological activities | Reference |
|
| (1) Breast cancer | MDA-MB-231 and MCF-7 | (i) Six fractions isolated by chromatography of methanol crude extract of CN bark | (i) Decrease in cell viability of MDA-MB-231 and MCF-7 cells by fractions A12 and A17 | Mutazah et al., 2019 |
| (ii) Two sulfur-containing compounds, including entadamide C and clinamide D were isolated from both fractions (A12 and A17) | (ii) IC50 of A12 to MDA-MB231 : 8.394 ± 0.086 μg/mL |
| (iii) IC50 of A12 to MCF-7: 8.007 ± 0.043 μg/mL |
| (iv) IC 50 of A17 to MDA-MB231 : 5.683 ± 0.064 μg/mL |
| (v) IC50 of A17 to MCF-7: 5.048 ± 0.083 μg/mL |
| (vi) Caspase-3 is the cellular target of both entadamide C and clinamide D by molecular docking analyses |
| 4T1 breast tumor-bearing mice | (i) Methanol extract of CN leaves | (i) Effective reduction in the number of mitotic cells, tumor weight, and tumor volume of 4T1 breast cancer model mice by high-dosage (1000 mg/kg) extract | Nik Abd Rahman et al., 2019 |
| MCF-7 | (i) Methanol and ethyl acetate extracts of CN roots | (i) Inhibition in proliferation of MCF-7 cells by methanol extract (IC50 : 35 μg/mL) and ethyl acetate extract (IC50 : 30 μg/mL) | Teoh et al., 2017 |
| (ii) 14 compounds and 7 compounds were isolated from ethyl acetate root extract and methanol root extract respectively | (ii) Noncytotoxic to NIH 3T3 cells at all concentration by methanol and ethyl acetate extracts |
| (iii) Methanol and ethyl acetate extracts: induction of apoptosis and decrease in BCL2 expression |
| (iv) No change in BAX expression |
| (v) Ethyl acetate extract: decrease in the mitochondrial membrane potential |
| MCF-7 | (i) Methanol crude extract and further fractionation by n-hexane, dichloromethane, chloroform, n-butanol, and water of CN leaves | (i) Crude extract (CN-Crd) itself had the strongest antioxidant scavenging activity, while water (CN-Aqu) fraction possessed the highest amount of total phenolic content (TPC) and total flavonoid content (TFC) | Ismail et al., 2017 |
| (ii) Identification by GC-MS of dichloromethane fraction (CN-Dcm) yields 14 compounds. Two most abundant compounds are linolenyl alcohol (29.10% at 12.023 min) and palmitic acid (23.84% at 11.133 min) | (ii) Hexane fraction (CN-Hex) displayed the highest antiproliferative effects on MCF-7 cells, with the IC50 of 50.34 ± 0.11 μg/mL, followed by the dichloromethane fraction (CN-Dcm) (IC50 : 65.95 ± 0.14 μg/mL) |
| MDA-MB-231 | (i) Methanolic extract from C. nutans leaves | (i) Antiproliferative activity of methanolic extract to MDA-MB-231 cells (IC50 : 18.67 μg/mL) | Quah et al., 2017 |
| (ii) The antiproliferative effects were possibly through the inhibition of CYP3A4 and CYP2E1 activities |
|
| (2) Cervical cancer | HeLa | (i) Methanol-hexane, methanol-dichloromethane (DCM), and methanol-water extracts of C. nutans | (i) Antiproliferative activities to HeLa cells for all extracts | Haron et al., 2019 |
| (ii) At least 28 compounds in DCM by GC-MS analysis and most of them were fatty acids | (ii) DCM: Highest antiproliferative activity (IC50 = 70 μg/mL) at 48 hours |
| (iii) DCM: induction of apoptosis and cell cycle arrest at S phase |
| HeLa | (i) Aqueous and methanol extracts of CN leaves | (i) Aqueous extract: strong cytotoxic effects (IC50 = 13 ± 0.82 μg/mL) | Yusmazura et al., 2017 |
| (ii) Aqueous extract: induction of apoptosis |
| (iii) No cytotoxicity to normal kidney cell lines (vero) by both extracts |
| (iv) No significant cytotoxic effect of methanol extract with no IC50 detected |
| HeLa | (i) The methanol extracts of leaves and buds of different plant ages, including 1-month-, 6-month-, and 1-year-old plant materials of C. nutans | (i) Highest 1,1-diphenyl-2-picrylhydrazyl (DPPH) activity in the extract of 1-year-old buds, with 50% of free radical scavenging (IC50) values of 64.6 μg/mL | Ghasemzadeh et al., 2014 |
| (ii) Highest total flavonoid (TF) (6.32 mg/g dry weight [DW]) and total phenolic (TP) compounds (18.21 mg/g DW) in 6-month-old buds | (ii) Higher ferric reducing antioxidant power (FRAP) activity in 6-month-old buds (488 μM of Fe(II)/g) than in 1-year-old buds (453 μM of Fe(II)/g) |
| (iii) Highest contents of caffeic acid (0.307 mg/g DW) and gallic acid (5.96 mg/g DW), phenolic acids in extracts of 1-year- and 6-month-old buds respectively | (iii) Decrease in cell viability of HeLa cells (IC50 = 56.8 μg/mL) by extracts of 6-month-old buds |
| (iv) Highest chalcone synthase (CHS, EC 2.3.1.74) activity in 6-month-old buds (9.5 nkat/mg protein) |
| HeLa | (i) Petroleum ether, ethyl acetate, and methanol crude extracts of Clinacanthus nutans by bioassay-guided fractionation | (i) Strongest cytotoxic activity against HeLa cells (IC50 = 18 μg/mL) by petroleum ether extract | Arullappan et al., 2014 |
| (ii) Highest radical scavenging activity in petroleum ether extract |
|
| (3) Colorectal cancer | HCT-116 | (i) Ethanol extract, hexane, ethyl acetate, and aqueous fractions of C. nutans leaves | (i) Strongest cytotoxicity (IC50 = 48.81 ± 1.44 μg/mL) to HCT-116 cells by C. nutans ethyl acetate fraction (CNEAF) | Wang et al., 2017 |
| (ii) CNEAF: induction of apoptosis; decrease in mitochondrial membrane potential; increase in reactive oxygen species (ROS); increase in bax expression; decrease in Bcl-2 and Bcl-X2 expression; activation of caspase−3, −9, −8, and −10 |
| (iii) Upregulation in death receptor 5 expression by CNEAF |
| (iv) Autophagy induction by CNEAF (increase in LC-3 level; decrease in p62 level) |
| HCT-116 | (i) Ethanolic, methanolic, 50% ethanolic, 50% methanolic, and water extracts of C. nutans leaves | (i) All crude extracts at concentrations of 200 and 100 μg/mL: no significant cytotoxicity on tested cell lines | Esmailli et al., 2013 |
| (ii) Fractions 3, 4, 14, and 16 of methanolic extract displayed significant cytotoxicity to HCT-116 cells at the concentration of 200 μg/mL |
| (iii) Fraction 14 : 84 ± 1.1% of growth inhibition at 100 μg/mL; other fractions <50% of inhibition |
|
| (4) Gastric cancer | SGC-7901 | (i) Isolation of a novel polysaccharide-peptide complex CNP-1-2 with molecular weight of 9.17 × 104 Da from CN leaves by a combination of methods | (i) Inhibition in cell viability of SGC-7901 cells concentration dependently (50, 100, 200 μg/mL) by CNP-1-2 | Huang et al., 2016 |
| (ii) CNP-1-2 consists of about 87.25% of carbohydrate and 9.37% of protein |
| (iii) Structure of CNP-1-2 was solved by methylation analysis, FT-IR, and 1H NMR spectroscopy analysis |
|
| (5) Liver cancer | HepG2 | (i) Five solvent extracts (hexane, chloroform, ethyl acetate, methanol, and water) of CN whole plants | (i) Both hexane and chloroform extracts displayed cytotoxic activity to HepG2 cells (IC50 of hexane extract: 150 μg/mL; IC50 of chloroform extract: 25 μg/mL) | Ng et al., 2017 |
| (ii) Hexane extract: induction of apoptosis and increase in the percentage of cells at sub-G1 stage; increase in the levels of ROS |
| (iii) Hexane extract: activation of caspases 8, 9, and 3/7 at high concentrations (≥100 μg/mL) |
| HepG2 | (i) Methanolic extract from C. nutans leaves | (i) Antiproliferative activity of methanolic extract to HepG2 cells (IC50: 13.33 μg/mL) | Quah et al., 2017 |
| (ii) The antiproliferative effects were possibly through the inhibition of CYP3A4 and CYP2E1 activities |
| HepG2 | (i) The extraction of phytochemicals, including the total phenolic content (TPC) and total flavonoid content (TFC), from Clinacanthus nutans by organic solvents (hexane, methanol, chloroform, and ethyl acetate) | (i) Cytotoxic activity of extracts to HepG2: methanol (IC50: 43.9367 μg/ml)> chloroform (IC50: 55.6112 μg/ml)> ethyl acetate (IC50: 62.0655 μg/ml)> hexane extract (IC50: 68.3807 μg/ml) | Hamid and Yahaya, 2016 |
| (ii) Chloroform extract: with highest total phenolic content (119.29 mg of gallic acid equivalent (GAE)) |
| (iii) Methanol extract: with highest total flavonoid content (937.67 mg of butylated hydroxytoluene (BHT)) |
| HepA xenograft mice model | (i) 30% ethanol extract (CN30) of CN | (i) CN30: decrease in tumor weight and volume | Huang et al., 2015 |
| (ii) 7 compounds were identified from CN30, including gallic acid, shaftoside, isoorientin, orientin, isovitexin, vitexin, apigenin 6, 8-di-C-α-L-arabinopyranoside | (ii) Apoptosis induction of hepatoma cells in vivo |
| (iii) Decrease in the expression of proliferation markers PCNA and p-AKT |
| (iv) Increase in expression of cleaved caspase-3; decrease in expression of BAX and Bcl2 |
| (v) Increase in the number of IFN-γ+ T cells and decrease in the number of IL-4+ T cells |
| | | (vi) Increase in the serum IFN-γ and interleukin-2 levels |
| HepG2 | (i) β-sitosterol-3-O- β glucopyranoside, β-sitosterol-3-O- β glucoside, and subfraction F-III were extracted and identified from ethyl acetate extract | (i) Strong cytotoxicity to HepG2 (IC50: 36.80 µg/mL) by subfraction F-III | Dan, 2014 |
| (ii) no effect on anti-oxidant assay by sub-fraction F-III |
|
| (6) Lung cancer | A549 | (i) Extracts by five solvents (hexane, chloroform, ethyl acetate, methanol, and water) of CN whole plants | (i) Highest cytotoxic activity of hexane extract to A549 cells (IC50: 74 μg/mL) | Ng et al., 2017 |
| (ii) Hexane extract: induction of apoptosis and increase in the percentage of cells at sub-G1; increase in the levels of ROS |
| (iii) Hexane extract: upregulation of caspases 8, 9, and 3/7 activities at high concentrations (≥100 µg/mL) |
| A549 | (i) Water extract of CN using kinetic extraction modeling to obtain maximum yield of flavonoids | (i) The best antiproliferative effects (IC50): 138.82 ± 0.60 µg/mL on two-dimensional cell culture of A549 cells | Fazil et al., 2016 |
| (ii) 18 hours of extraction was determined to obtain the maximum content of flavonoids |
|
| (7) Lymphoma and leukemia | MOLT-4 and SUP-T1 | (i) Methanol extract of leaves of CN, then extracted by hexane (MH), methanol (M), ethyl acetate (ME), and butanol (MB) respectively | (i) Strong decrease in the cell viability of MOLT-4 cells by the acetone extract (MHA) | Lu et al., 2018 |
| (ii) MH fraction was further extracted by hexane (MHH) and acetone (MHA) | (ii) Decrease in the cell viability of SUP-T1 cells dose dependently |
| (iii) MHA: induction of apoptosis; decrease in the mitochondrial membrane potential; increase in the levels of ROS; increase in calcium ions in SUP-T1 cells |
| (iv) MHA: increase in protein levels of active caspase−3, −7, and −8 in SUP-T1 cells |
| (v) MHA: decrease in Bcl-xl and Bcl-2 expression; increase in Bim, Bak, and cytochrome C expression in SUP-T1 cells |
| (vi) MHA: induction of ER stress (increase in CHOP and IRE-1α expression) in SUP-T1 cells |
| (vii) MHA: decrease in hexokinase II expression in SUP-T1 cells |
| (viii) MHA: increase in TNF-1α, NF-κB, and DR5 expression at concentration of 50 μg/mL in SUP-T1 cells |
| K562 | (i) Chloroform, methanol, and water extracts of CN leaves | (i) Highest antiproliferative effect (91.28 ± 0.03%) of chloroform extract at 100 μg/ml to K-562 cells | Yong et al., 2013 |
| Raji | (i) Chloroform, methanol, and water extracts of CN leaves | (i) Highest antiproliferative effect (88.97 ± 1.07%) of chloroform extract at 100 μg/ml to Raji cells | Yong et al., 2013 |
|
| (8) Head and neck cancer | HSC-4 | (i) Silver nanoparticles (AgNps-CN) of CN leaves extract | (i) Cytotoxicity of AgNps-CN to HSC-4 cells (IC50: 1.61 ± 0.14 μg/mL) | Yakop et al., 2018 |
| (ii) Nontoxicity of AgNps-CN to 3T3-L1 cells at high concentration (3.00 μg/mL) |
| (iii) AgNps-CN: induction of apoptosis and cell cycle arrest at G1 phase of HSC-4 cells |
| (iv) AgNps-CN: increase in Bax expression; decrease in Bcl-2 expression |
| CNE-1 | (i) Five solvent extracts (hexane, chloroform, ethyl acetate, methanol, and water) of CN whole plants | (i) Highest cytotoxic activity of hexane extract to CNE-1 cells (IC50: 116.7 μg/mL) | Ng et al., 2017 |
| (ii) Antiproliferative activity of ethyl acetate extract to CNE-1 cells at 300 µg/mL |
| (iii) Hexane extract: induction of apoptosis and increase in the percentage of cells at sub-G1, increase in ROS |
| (iv) Hexane extract: activation of caspases 3/7, 8, and 9 at the concentrations of ≥100 µg/mL |
|
| (9) Skin cancer | D24 | (i) The crude methanol extracts of CN from 11 different locations in Malaysia, Thailand, and Vietnam | (i) More toxicity of extracts from higher elevations with lower temperature to D24 melanoma cells | Fong et al., 2016 |
| (ii) Highest cytotoxic activities were found in Chiang Dao, Chiang Mai, Thailand; the half maximal effective concentration (EC50): 0.95 mg/mL, 24 hours; EC50: 0.77 mg/mL, 72 hours |
| (iii) Induction of apoptosis by Chiang Dao extract |
|
