Table 2 Comprehensive overview of the molecular mechanisms of DBCLS anticancer activity
Anticancer mechanism | Molecular and cellular target | Tested DBCL | Experimental model | Dosage | Anticancer effect | Refs. |
|---|---|---|---|---|---|---|
Apoptosis induction | Mitochondrial apoptotic pathway (Cytochrome c, Caspases) | Schisandrin B | Human gallbladder cancer GBC-SD and NOZ cell lines | Schisandrin B at 0, 30, 60 and 90 μmol/L | ↓ Cell viability ↑ Apoptosis | [129] |
Cell cycle arrest | G0/G1, G1/S, G2/M phases | Schisandrin B | Gastric cancer SGC-7901 cell line | Schisandrin B (75 μM), or apatinb (60 μM) with schisandrin B (75 μM) | ↓ Cell proliferation ↓Invasion, ↓Migration ↑Efficacy of apatinib | [132] |
Gomisin A | Cervical cancer HeLa cell line Mice C57BL/6 (in vivo) mouse melanoma B16F10 cell line and human melanoma cell line A375SM (in vitro) | Gomisin A at 10, 30 and 100 µM in the presence or absence of TNF-α (20 ng/mL) gomisin A at 2, 10, and 50 mg/kg orally administered to mice once a day, mice were sacrificed after 14 days; gomisin A at 0, 25, 50, 100 µM gomisin A; for 24 h | ↓ Cell viability ↓ Migration and invasion | |||
Schisantherin A | Human tongue squamous HN4 cell line, macrophage-like RAW264.7 cell line, human gastric MKN45 and SGC-7901 cancer cell lines, human breast cancer MCF7 and MDA-MB-231 cell lines | Schisantherin A at 0 nM, 500 nM, 1 μM and 2.5 μM | ↑ Anti-proliferative effect ↑ Cell cycle arrest | [134] | ||
ROS generation | Oxidative stress response | Gomisin L1 | Ovarian cancer A2780 and SKOV3 cell lines (in vitro) | Gomsin L1 at 3.12, 6.25, 12.5, 25, 50 and 100 µM | ↑ Apoptosis via ROS production | [130] |
Autophagy induction | mTOR | Gomisin J | Breast cancer MCF7 and MDA-MB-231, and normal MCF10A cell lines (in vitro) | Gomisin J at 10–30 µg/mL | ↑ Autophagy-mediated cell death | [131] |
Inhibition of proliferation, invasion, metastasis | MMP activity modulation | Schisandrin B | Prostate cancer DU145 and LNCaP cell lines (in vitro) | Schisandrin B at 0, 50, 100, 150 and 200 µM | ↓ Cell growth ↓ Migration ↑ Invasion ↑ Apoptosis | [135] |
Chemotherapy resistance modulation | Sensitization to chemotherapy agents, P-glycoprotein expression | Schisandrin B | Breast cancer MDA-MB-435S, MCF-7/ADR, MCF-7 and ovarian cancer A2780 cell lines (in vitro) | Schisandrin B at 10 μM | ↑ Sensitivity to doxorubicin ↑ Apoptosis ↓ Tumor growth and migration | |
Cervical cancer (Caski cells) BALB/c nude mice xenografts (in vitro and in vivo) | In vivo experiments Schisandrin B at 20 mg/kg b.w | ↓ Cell viability ↓ Colony formation ↑ Apoptosis ↓ Tumor cell invasion ↑ Cytotoxic effect of docetaxel | [142] | |||
Schisandrin B combined with epirubicin | Breast cancer MDA-MB-435S, MCF-7/ADR, MCF-7 and ovarian cancer A2780 cell lines (in vitro) | Schisandrin B at 10 μM | ↑ Cytotoxic effect ↓ Vascular mimicry | [137] | ||
Schisandrin B | Gastric cancer SGC7901 and BGC823 cell lines (in vitro) | Schisandrin B at 0, 10, 25, 50, 100, 200 μM | ↑ Cytotoxic effect by arresting G0/G1 cell cycle | [138] | ||
Schisandrin B | Gastric cancer SGC-7901 cell line (in vitro) | Schisandrin B at 75 µM | ↑ Invasion and migration of apatinib ↑ Cytotoxic drug-induced apoptosis | [132] | ||
Schisandrin B | Gastric cancer BGC-823 cell line (in vitro) and nude mouse model bearing allograft (in vivo) | Schisandrin B at 0.1 μM (in vitro), 5 mg/kg b.w. (in vivo) | ↓ Tumor metastasis; Selective accumulation at tumor site | [140] | ||
Regulation of signaling pathways | MAPK, PI3K/Akt, NF-κB, Wnt/β-catenin | Schisandrin B | Prostate cancer DU145 and LNCaP cell lines (in vitro) | Schisandrin B at 0, 50, 100, 150 and 200 µM | ↓ Cell proliferation; ↑ Apoptosis | |
Gomisin G | Breast cancer MDA-MB-231 and MDA-MB-468 cell lines (in vitro) | Gomisin G at 1, 5 and 10 µM |