Table 2 The anticancer mechanisms of cucurbitacins tested in vitro and in vivo experimental cancer models
From: Cucurbitacins as potential anticancer agents: new insights on molecular mechanisms
Tested cucurbitacin | Experimental model | Anticancer mechanisms | Refs. |
|---|---|---|---|
Cucurbitacin B
| In vitro Melanoma cells A375 | ↓proliferation ↓MAPK | [79] |
In vivo Mice NOD-SCID xenograft melanoma model | ↑ cytotoxicity ↓tumour growth | ||
In vitro Gastric cancer cells SGC7901/DDP | Reversed multi-drug resistance ↓HIF-1a, ↓P-gp ↑apoptosis, ↑autophagy ↓CIP2A/PP2A/mTORC1, ↓mTORC1, ↓PP2A | [80] | |
In vitro Hepatoma human cells HepG2, BEL-7402 | ↓cell invasion, ↓migration ↓MMP-9,↓ ERK 1/2,↓ p38, ↓Akt | [81] | |
In vitro Non-small cells lung cancer (NSLC) H1299 | ↑epigenetic modifications ↓histone deacetylase ↓DNA methyltransferase ↑tumour suppressor genes: ↑CDKN1A, ↑CDKN2A ↓oncogenes ↓β-catenin, ↓Wnt3, ↓Wnt3a | ||
In vivo Mice Lung tumourigenesis model | ↓angiogenesis | ||
In vitro Human cholangiocarcinoma cells KKU-100 | Antiproliferative Cell cycle arrest at the G2/M phase ↓cyclin A, cyclin D1 ↑p21, ↑p53, ↓FAK, ↓EGFR, ↓HER2 ↓FAK/PI3K/PDK1/AKT, FAK/p53 | [84] | |
In vitro Breast cancer cells MDA-MB-231, SKBR3- MCF-7, 4T-1 | ↓ cells growth ↓HER2, ↓EGFR, ↓ILK1/ YB-1/Twist ↓ITGA6, ↓ITGB4 | [85] | |
In vivo Mice MDA-MB-231 athymic nude model | ↓tumour volume | ||
In vitro Breast cancer cells MDA-MB-231 cells | ↑apoptosis, ↑morphologic changes ↑irregular polymerization of the microtubule ↑arrest at the G2/M cell cycle phase ↓c-Myc, ↓nucleophosmin/B23 | [86] | |
In vitro Breast cancer cells MDA‐MB‐231, SKBR‐3 | ↓cell migration ↓RAC1/CDC42/RhoA ↓FAK, ↓RAC1, ↓CDC42 | [87] | |
In vivo Mice BALB/c nude bearing SKBR‐3 cells | ↓metastasis | ||
In vitro Prostate cancer cells LNCaP, PC-3 | ↑apoptosis ↑Caspase 3, ↑ Caspase 7 ↑Sub-G0/G1 phase | [88] | |
In vivo Mice PC-3 xenograft growth model | ↓ATP citrate lyase (ACLY) | ||
In vitro Human glioblastoma cells line U87 | ↓angiogenesis ↓α5β1 | [69] | |
Cucurbitacin D
| In vitro Cervical cancer cells CaSki, SiHa | ↓tumor cells growth, ↓metastasis ↑annexin V, ↑ PARP ↑cell cycle arrest at the G1/S phase ↑CDK4, ↑cyclin D1 ↓RB protein phosphorylation ↓PI3K/AKT, ↓STAT3, ↓MMP9, ↓c-Myc | [70] |
In vivo Athymic nude mice bearing CaSki cells | ↓ tumour growth | ||
In vitro Pancreatic cancer cells AsPC-1, Capan-1 | ↑apoptosis ↑cell cycle arrest at the G2/M phase ↑ROS, ↑p38, ↑c-Jun, ↑ROS/p38 ↓cyclin B1, ↓PARP ↓phospho-cdc2, ↓phospho-cdc25c ↑p21, ↓cyclin/CDK ↑caspases 7, ↑caspase 8 | [91] | |
In vitro Non-small cells lung cancer NSCLC-N6 cells | cell cycle arrest at the G1 phase ↑CDK1 mRNA ↓p53 | [72] | |
Cucurbitacin E
| In vitro Glioblastoma cells GBM8401, U-87-MG | ↓cell proliferation, ↑apoptosis ↑ G2/M phase of the cell cycle ↓mitosis, ↓CDC2, ↓cyclin B1 ↓GADD45β, ↓CDC2/cyclin B1 | [73] |
In vitro A549 non-small cells lung cancer NSCLC cells lung cancer cells | ↑apoptosis ↑EGFR, ↑EGFR/MAPK, ↑ERK1/2, ↓MEK1/2 ↑caspases -3, ↑caspase -9, ↓survivin, ↓STAT3 ↓cyclinA2, ↓cyclinB1, ↓cyclin E1 ↑G1/G0 phase of the cell cycle | [74] | |
In vitro GBM8401malignant glioma cells GBM8401 | antiproliferative, ↓cell growth ↑cell cycle arrest at the G2/M phase ↑GADD45γ, ↓B1/CDC2 | [75] | |
Cucurbitacin I
| In vitro SKOV3 ovarian cancer cells PANC-1 pancreatic cancers cells | ↑apoptosis, ↑ autophagy ↑ERS, ↑IRE1α, ↑PERK, ↑caspase-12 ↑CHOP, ↑Bax | [76] |
In vitro colon cancer cells SW480 | ↓cell viability, ↑apoptosis, ↓proliferation ↑cell cycle arrest at the G2/M phase ↓cyclin A, ↓cyclin B1, ↓CDC25C, ↓CDK1 ↓ CDK1/cyclin B1, ↓caspases -3, -7, -8, -9 | [77] | |
In vivo Mice Syngeneic transplanted CT-26 BALB/c | ↓tumour growth ↓proliferation | ||
Cucurbitacin II
| In vitro Non-small cells lung cancer NSCLC lung cancer cells A549 | ↑apoptosis, ↑cell cycle arrest ↓EGFR, ↓EGFR/MAPK, ↓cyclinB1, ↓ERK1, ↓MEK1, ↓MEK2, ↑survivin, ↑BRAF, ↑Raf1, ↑ERK2, ↑STAT3, ↓ERK1, ↓MEK1 | [78] |
↑apoptosis, ↓STAT3 ↑G2/M phase cell cycle arrest, ↓EGFR/MAPK | [79] | ||
↓cell growth, ↑apoptosis ↓ STAT3, ↓EGFR | [80] |
