Table 3.
Mechanism involved and pharmacological outcomes from various anticancer investigations on shikonin and its derivatives.
| Compounds | Cell lines/In vitro/In vivo assay | Mechanism involved | Types of cancer | References |
|---|---|---|---|---|
| Shikonin | Human normal lung fibroblast cell line CCD19 and human NSCLC cell lines (HCC827, H1650 and H1975) | Induces EGFR degradation causes deactivation of Tyr1173 and Tyr1068 of EGFR; Inhibits TrxR1 to activate ROS-mediated apoptosis |
Gefitinib-resistant non-small cell lung cancer | Li et al., 2017 |
| Human epithelial colorectal adenocarcinoma Caco-2 cells. AOM/DSS model. |
Inhibition of COX-2, iNOS and IL-6 via deactivation of NFƙB; Inhibits Bcl-2 and activates Caspase-3 |
Colon cancer | Andújar, Ríos, Giner, & Recio, 2013 | |
| Normal human colon epithelial cell line (NCM460), well-differentiated colon carcinoma cell lines (HT29 and HCT116), poorly differentiated colon carcinoma cell line (SW480). Nude mouse tumor xenograft model |
Overexpression of SIRT2; Inhibits the viability of SW480 cells and arrests the cell cycle at the G2/M stage; Inhibition of ERK1/2 phosphorylation |
Colorectal cancer | Zhang et al., 2017 | |
| MCF-7 and SK-BR-3 cells | Downregulation of ERα, GPER, EGFR and p-ERK expressions; Inhibits the proliferation in MCF-7 and SK-BR-3 cells; Arrest cell cycle at G0/G1 phase in MCF-7 and induce apoptosis in SK-BR-3 cells |
Breast cancer | Yang et al., 2019 | |
| Human lung cancer cells (A549) Nude mouse tumor xenograft model |
Significant increase in RIP1 levels leading to necroptosis | Non-small cell lung cancer | Kim et al., 2017 | |
| Human colon cancer cell lines HCT116, SW480 and human normal colon mucosal epithelial cell line NCM460. | Decreased Bcl-2 and Bcl-xl expression; Increased caspase 3 and 9 activities. Depolarization of mitochrondrial membrane potential |
Colon cancer | Liang et al., 2017 | |
| Myelogenous leukaemia cell line (K562cells), breast cancer cell line (MCF-7cells) and cervical cancer cells (HeLa cells) Xenograph tumour model | Irreversible inhibition of human recombinant CDC25 phosphatases; Inhibit dephosphorylation of CDK1 thereby inducing cell cycle arrest at G2/M phase |
Cancer | Zhang et al., 2019 | |
| Human lung cancer cells (A549) Nude mouse tumor xenograft model |
Suppression of NEAT1 and Akt signaling | Paclitaxel-resistant non-small cell lung cancer | Zang, Rao, Zhu, Wu, & Jiang, 2020 | |
| Breast cancer cell line (MCF-7 cells) | Downregulation of Bax expression and reduced exosomal secretion leading to suppress proliferation | Breast cancer | Wei et al., 2016 | |
| Human colon cancer cell line (SNU-407)Terminal deoxynucleotidyl transferase-mediated digoxigenin dUTP nick-end labeling (TUNEL) assay. |
Induces the mitochondrial dysfunction via downregulation of Bcl-2 and upregulation of Bax, Caspase-3 and Caspase-9; Activation of MAPK Pathway. Increased Ca2+ levels leading to ER stress |
Colon cancer | Han et al., 2019 | |
| Murine mammary cancer (4 T1) and human breast cancer cells (MDA-MB-231) Orthotopic model of murine mammary cancer cells. |
Activation of p38 and JNK signaling pathways; Increase caspase3/7 activity; Inhibits proliferation, migration and invasion ability of cells |
Breast cancer | Xu et al., 2019 | |
| Human breast cancer cells (MDA-MB-231) | Reduced expression of miR-17-5p and upregulation of PTEN expression with decreased levels of Akt and p-Akt leads to EMT suppression | Triple negative breast cancer | Bao et al., 2020 | |
| Human ovarian cancer cell (SKOV3) | Downregulation of Bcl-2, AKT and PI3K whereas upregulation of Bax, Caspase-3 and Caspase-9 | Ovarian cancer | Zhang et al., 2020 | |
| Human melanoma (A375) and normal human liver-derived cells (MIHA) Zebrafish Tumor Model |
Reduced expression of STAT3 dimer. Decreased levels of Bcl-2, Mcl-1, MMP-9 and MMP-2 |
Malignant melanoma | Cao et al., 2020 | |
| Human colorectal adenocarcinoma (SW620 and HCT116 cell lines) Subcutaneous tumor mouse model |
Induce autophagosome formation via LC3 cleavage; Upregulate expression and promote galectin-1 dimerization |
Colorectal carcinoma | Zhang et al., 2020 | |
| Hepatocellular carcinoma cells lines (LM3, SMMC-7721, Huh-7, and HepG2) and a normal liver cell line (LO2) | Downregulates the expression of PKM2; Increased expression of Bax, cyto C, cleaved Caspase-9, and cleaved Caspase-3, and decreased expression of Bcl-2 |
Hepatocellular Carcinoma | Liu et al., 2020 | |
| Hepatocellular carcinoma cell lines (Huh-7 and HepG2) | Modulation of the SMAD7/TGF‐β signaling pathway through regulation of miR‐106b | Hepatocellular carcinoma | Li & Zeng, 2020 | |
| Shikonin, acetyl shikonin, and β,β-dimethyl acryl shikonin | Human breast cancer cells (MDA-MB-231) and Murine mammary cancer (4T1). | Shikonin was found most potent against TNBC cell lines; Upregulates E-catherin levels whereas downregulates N-cadherin and vimentin levels; Stimulate β-catenin degradation through enhanced GSK-3β levels |
Triple-negative breast cancer | Chen et al., 2019 |
| Shikonin, Deoxyshikoninand β,β-Dimethyl acrylshikonin | Human amelanotic malignant melanoma cell line A375 (CRL1619), mouse metastatic melanoma cell line B16-F10 (CRL-6475) and mouse nonmetastatic melanoma cell line B16-F0 (CRL6322), | Induces p53-mediated cell cycle arrest;Stimulates ROS -mediated Endoplasmic Reticulum (ER) stress. Activation of p-ERK, p-p38, Caspase-3 and Caspase-9 |
Skin cancer | Ng, Upton, Leavesley, & Fan, 2020 |