Table 5.
Type of Cancer | IC50 | Combination Treatment | Combination Effect | Ref |
---|---|---|---|---|
In Vitro/In Vivo | ||||
Breast cancer | In vitro: MCF-7, MDA-MB-231 In vivo: NOD/SCID mice bearing MDA-MB-231 or MCF-7/ADR |
ISL + 5-FU ISL + epirubicin ISL + taxol |
ISL possess chemosensitizing effects via activation of autophagy ISL limited the self-renewal and differentiation abilities of breast CSCs via GRP78/β-catenin/ABCG2 signaling |
[40,56] |
Colon cancer | In vitro: HT29 | ISL + TRAIL | ISL up-regulates a TRAIL receptor DR5 protein overcomes TRAIL resistance in colon cancer | [72] |
In vitro: HTC116 | ISL + 5-FU | ISL-induced p62/SQSTM1 expression mediated apoptosis by reducing caspase-8 activation | [73] | |
In vivo: CT26 murine colon cancer cells | ISL + cisplatin | ISL reduced tumor sizes without any detectable nephrotoxicity or hepatoxicity. ISL suppressed cisplatin-induced kidney and liver damage led to a syngeneic effect for anti-cancer |
[75] | |
In vitro: CEM/ADR 5000 cells and Caco-2 cells | ISL + doxorubicin ISL + doxorubicin+ saponin digitonin |
In combined therapy, ISL was identified as potential multidrug resistance (MDR) modulator which serves as a chemo-adjuvant therapy | [11] | |
Melanoma | In vivo: MM xenograft models | ISL + adriamycin | ISL could inhibit the growth of MM via blocking IL-6 ISL synergistically enhanced the anti-myeloma activity of adriamycin |
[105] |
Liver cancer | In vitro: HepG2 In vivo: BALB/c bearing HepG2 |
ISL + Radiochemotherapy | ISL induced oxidative stress (ROS) by disturbing the redox status and ultimately enhancing the radiosensitivity ISL on radiosensitization via Nrf2-Keap1 pathway |
[111,143] |
[57,140] | ||||
Cervical cancer | In vitro: HeLa cell | ISL + ROS scavengers |
ISL induced apoptosis by increasing intracellular ROS levels | [144] |
In vivo: KM mice bearing U14 | ISL + cyclophosphamide | ISL enhanced antitumor activity of CP in vivo and decreased the micronucleus formation DNA strand breaks | [145] | |
Gastric cancer | In vitro: MKN45 | ISL + 5-FU | ISL downregulated GRP78 and CSCs- marker, ABCG2, LGR5, CD24 and CD44 to enhance chemosensitivity with combination of 5-FU | [146] |
Leukemia | In vitro: T-ALL cells | ISL + DOX ISL + MTX |
ISL may be a valuable adjunct for cancer therapy to treat otherwise drug-resistant tumors | [96] |
Lung cancer | Pulmonary metastasis model: BALB/c mouse bearing Renca cells | ISL + 5-FU | ISL suppressed tumor proliferation, potentiated nitric oxide production by lipopolysaccharide-stimulated macrophages, and facilitated cytotoxicity of splenic lymphocytes in vitro | [139] |
Asthma | In vitro: D10 cells In vivo: OVA sensitization/ 7, 4′-DHF challenge |
ISL + ASHMI™ | ISL increased IFN-γ expression involving anti-inflammatory effect ISL reduced eosinophilic pulmonary inflammation via suppressed Th2 cytokines, IL-4 and IgE production |
[147] |
Oral cancer | Oral squamous cell carcinomas In vivo: nude mice bearing OSCC |
ISL + cisplatin | ISL mediated GRP78 regulation serves as chemotherapy adjuvant | [60] |
Bladder cancer | T24 | ISL + cisplatin | ISL treatment with cisplatin increases cell death in bladder cancer cells | [148] |
Uterine sarcoma | MES-SA/Dx5, MES-SA/Dx5-R | ISL + doxorubicin | ISL enhanced chemosensitivity via inducing apoptosis and autophagy ISL inhibits mTOR pathway |
[142] |
Kidney cancer | LLC-PK1 | ISL + cisplatin | ISL pretreatment induces ER stress and produces hormesis to protect against CP-induced nephrotoxicity | [149] |
Neuroblastoma | In vitro: MYC-amplified NB cells SK-N-BE(2) and IMR-32 |
ISL + cisplatin | Treated ISL with cisplatin resulted in loss of cell viability greatly, acting as a potential adjunct therapy | [129] |