Table 3.
Targeting SREBP-1-mediated lipogenesis in different cancers.
| Treatment | Targets | Cancer type | Molecular mechanism | Refs |
|---|---|---|---|---|
| Fatostatin | SREBP-regulated metabolic pathway and AR signaling | Prostate cancer | Suppresses cell proliferation and colony formation and causes G2/M cell cycle arrest and cell death in both androgen-responsive or insensitive cancer cells | (136) |
| Fatostatin | SREBP activity | Various cancers | Possesses antitumor anti-mitotic properties by inhibiting tubulin polymerization and activating spindle assembly checkpoints | (137) |
| Fatostatin | Accumulation of polyunsaturated fatty acids | Breast cancer | Induces cell cycle arrest and apoptosis through the accumulation of lipids in response to ER stress, not by SREBP activity in estrogen receptor-positive cancer cells | (138) |
| Fatostatin | SREBP-1/NF-κB pathway | Endometrial cancer | Reverses progesterone resistance to inhibit proliferation and induces apoptosis both in vitro and in vivo models | (139) |
| Fatostatin and PF429242 | SREBP-1 and its downstream targets, FASN, SCD-1 | Pancreatic cancer | Inhibits cell viability and proliferation in a time- and dose-dependent manner | (17) |
| Fatostatin combined with tamoxifen | PI3K/Akt/mTOR pathway | Breast cancer | Significantly suppresses cell viability and invasion and regulates apoptosis and autophagy in the cell and mouse xenograft models | (140) |
| Nelfinavir | Intramembrane proteolysis of SREBP-1 and ATF6 | Liposarcoma | Induces the increases of SREBP-1 and ATF6 resulted from S2P inhibition against ER stress and caspase-mediated apoptosis | (141) |
| Nelfinavir | Intramembrane proteolysis of SREBP-1 and ATF6 | Prostate cancer | Inhibits androgen receptor activation and nuclear translocation of SREBP-1 to cause unprocessed SREBP-1 and ATF6 accumulations for the inhibition of proliferation and unfolded protein response | (142) |
| Nelfinavir and its analogs, #6, #7, and #8 | Intramembrane proteolysis of SREBP-1 and ATF6 | Prostate cancer | Induces the increases of SREBP-1 and ATF6 resulted from S2P inhibition against ER stress and apoptosis | (143) |
| Osimertinib | SREBP-1 | Non-small cell lung cancer | Facilitates SREBP-1 degradation, reduces the levels of its targets and lipogenesis to overcome the acquired resistance of EGFR inhibitors | (144) |
| Sorafenib | ATP/AMPK/mTOR/ SREBP-1 |
Hepatocellular carcinoma | Suppresses ATP production to activate AMPK and reduce SREBP-1 and phosphorated mTOR levels to disrupt SCD-1-mediated synthesis of monounsaturated fatty acids | (145) |
| ASC-J9 | AR/SREBP-1/FASN and PI3K/Akt/SREBP-1/FASN | Prostate cancer | Suppresses cell growth and invasion in both AR-dependent and AR-independent manner | (146) |
| Proxalutamide | SREBP-1/ACL/ACC/FASN | Prostate cancer | Inhibits the proliferation and migration, induces the caspase-dependent apoptosis, and diminishes the level of lipid droplets, which also overcome the resistance of AR-targeted therapy by decreasing AR expression | (147) |
| Leelamine | SREBP-1, ACLY, FASN, and SCD | Prostate cancer | Suppresses fatty acid synthesis in the cancer cells and tumor xenograft, not affected by AR status | (148) |
| Valproic acid | C/EBPα/SREBP-1 pathway (FASN, ACC1) | Prostate cancer | Inhibits cell viability and lipogenesis and induce apoptosis in the cancer cells | (149) |
| Beta2-microglobulin antibody | MAPK, SREBP-1 and AR | Prostate cancer | Decreases cell proliferation, induces apoptosis, and reduces AR expression to suppress tumor growth and progression | (150) |
| N-Arachidonoyl dopamine | SREBP-1/ERK1/2 pathways | Breast cancer | Inhibits cell migration, EMT, and stemness and causes decreased cholesterol biosynthesis | (151) |
| SI-1 | SREBP-1 activation | Hepatocellular carcinoma | Enhances the sensitivity to radiofrequency ablation in cancer cells, xenograft tumors, and the patients | (152) |
| Docosahexaenoic acid | Precursor and mature SREBP-1, FASN | Breast cancer | Inhibits cancer cell proliferation induced by estradiol and insulin, which is dependent on Akt phosphorylation, not ERK1/2 phosphorylations | (153) |
| Phytol and retinol | SREBP-1, FASN, and farnesyl-diphosphate farnesyltransferase | Glioblastoma | Have cytotoxic effects in a dose-dependent manner and inhibit cholesterol and/or fatty acid biosynthetic pathways | (154) |
| Platinum complexes, C2, C6, C8 | SREBP-1-regulated metabolic pathway (LDLR, FASN, HMGCR) | Breast, liver, and lung cancer | Inhibits invasion, migration, and cancer stem cell formation and induce apoptosis in vitro | (155) |
| PB@LC/D/siR | SREBP-1 and SCD-1 | Bone metastatic castration-resistant PCa | Shows the enhanced antitumor effects with the characteristics of deep tumor penetration, high safety, and bone protection | (156) |
| 6-Shogaol | Akt, p70S6K, and AMPK-mediated SREBP-1 levels | Colorectal cancer | Attenuates the effect of adipocyte-conditioned medium on 5-FU resistance | (157) |
| Ilexgenin A | HIF-1α/SREBP-1 pathway | Colorectal cancer | Inhibits azoxymethane/dextran sulfate sodium-induced inflammatory colitis and reverses colorectal cancer-associated metabolites by reprogramed lipid metabolism | (158) |
| RA-XII | SREBP-1, FASN, and SCD | Colorectal cancer | Decreases cell motility, tumor growth, and metastasis by restraining lipogenesis | (159) |
| Berberine | SCAP/SREBP-1 pathway | Colon cancer | Inhibits cell proliferation and induces G0/G1 cell cycle arrest and regulates the levels of lipogenic enzymes in the in vitro and in vivo studies | (160) |
| Cinobufotalin | SREBP-1 expression and the interaction with sterol regulatory elements | Hepatocellular carcinoma | Induces cell cycle G2-M arrest and apoptosis and inhibits cell proliferation via the inhibition of de novo lipid synthesis | (161) |
| Emodin | SREBP-1 and its downstream targets, ACLY, ACCα, FASN, and SCD-1 | Hepatocellular carcinoma | Triggers apoptosis and reduces mitochondrial membrane potential to play an anticancer effect | (162) |
| Betulin | SREBP-1 | Hepatocellular carcinoma | Inhibits cellular glucose metabolism to prevent metastatic potential and facilitates the inhibitory effect of sorafenib | (163) |
| Theanaphthoquinone | EGF-induced nuclear translocation of SREBP-1 and FASN expression | Breast cancer | Decreases cell viability and induces cell death by regulating ERK1/2 and Akt phosphorylation and EGFR/ErbB-2 pathways | (164) |
| Piperine | SREBP-1 and FASN expression | HER2-overexpressing breast cancer | Inhibits proliferation, induces apoptosis, and enhances sensitization to paclitaxel by regulating ERK1/2, p38 MAPK, and Akt signaling pathways | (165) |
| Vitexin and syringic acid | GRP78/SREBP-1/SCD-1 | Breast cancer | Inhibits cell proliferation and impairs tumor growth by regulating cellular membrane and lipid droplet | (166) |
| Ginsenoside Rh2 | SREBP-1 nuclear translocation and FASN | Non-small cell lung cancer | Enhances the immune effect and has a synergistic antitumor effect with cyclophosphamide | (167) |
| α-Mangostin | AMPK activation and nuclear SREBP-1 translocation | Gallbladder cancer | represses cell proliferation, clone formation ability, and de novo lipogenesis; induces cell cycle arrest and apoptosis; and enhances gemcitabine sensitivity | (168) |
| Quercetin | SREBP-1 and the interaction with O-linked N-acetylglucosamine transferase | Cervical cancer | In cervical carcinoma, quercetin, a naturally occurring dietary flavonoid, decreases cell proliferation and induces cell death in Hela cells by reducing the O-GlcNAcylation of AMPK | (169) |
| Resveratrol | SREBP-1 | Pancreatic cancer | Induces gemcitabine chemosensitivity and suppresses sphere formation and the markers of cancer stem cells in both in vitro and in vivo models | (170) |
| Timosaponin A3 | SREBP-1 and its downstream targets, FASN, ACC | Pancreatic cancer | Inhibits cell viability and induces cell cycle arrest, apoptosis in the cancer cells and xenograft model, which is independent in the Akt/GSK-3β pathway | (171) |
| Ethanol extract of Ganoderma tsugae | SREBP-1 and its downstream genes, AR, PSA | Prostate cancer | Inhibits cancer growth and activates apoptosis by blocking the SREBP-1/AR axis | (172) |
| Ethanol extract of Davallia formosana | SREBP-1/FASN/lipogenesis and AR axis | Prostate cancer | Suppresses cancer proliferation, migration, and invasion by inhibiting the levels of SREBP-1, FASN, AR, and PSA in in vitro and in vivo experiments | (173) |
| Cell suspension culture extract from Eriobotrya japonica | SREBP-1/FASN and AR signaling pathways | Prostate cancer | Inhibits cell growth, migration, and invasion by decreasing the SREBP-1/FASN-mediated lipid metabolism and AR signaling pathway in the cell and mouse models | (174) |
| Astragalus polysaccharides | miR-138-5p/SIRT1/SREBP-1 pathway | Prostate cancer | Inhibits proliferation and invasion in a dose- and time-dependent manner and blocks tumorigenesis and lipid metabolism by the miR-138-5p/SIRT1/SREBP-1 pathway | (175) |
| TJ001 | ACC expression, SREBP-1 proteolytic cleavage, | Prostate cancer | Has significant cytotoxicity, induces cell cycle arrest at the G1/S stage, and inhibits lipid accumulation in D145 cells by regulating the AMPK/mTOR pathway | (176) |
| CO2 supercritical extract of Yarrow | SREBP-1, FASN, and SCD | Pancreatic cancer | Induces cytotoxicity in cancer cells and diminishes tumor growth of the xenograft mouse model | (177) |