Table 5.

ISL combined with other cancer treatment.

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]