Table 1.

The Effects of Morusin on Subtypes of Cancer.

Organ	Cell Type	Effects on Cellular Processes	System	Reference
Liver	LO2 HepG2 Hep3B	Apoptosis induction & angiogenesis inhibition increases the expression of caspase-3 and the Bax/Bcl-2 expression ratio inhibits tube formation of HUVECs in vitro and suppresses constitutive as well as IL-6-induced STAT3 phosphorylation	in vitro in vivo	[47]
Liver	SK-Hep1	Anti-tumor progression through suppressing STAT3 and NF-kB suppresses cell-matrix adhesion, cell motility and cell invasion at non-cytotoxic concentration increases the expression of E-cadherin and decreases the expression of vimentin and α2-, α6-, β1-integrin	in vitro in vivo	[34]
Lung	A549	Apoptosis induction & cell migration suppression induces apoptosis by loss of mitochondrial function and increases the antioxidant activities by up-regulation of SOD inhibits the invasion and migration by down-regulation of COX2 and VEGF at the transcription level	in vitro	[52]
Lung	H1299 H460 H292	Apoptosis induction by suppression of EGFR/STAT3 activation inhibits phosphorylation of EGFR and STAT3 and shows potential to treat advanced NSCLC with acquired resistance to EGFR tyrosine kinase inhibitor The docking analysis: morusin directly binds to the tyrosine kinase domain of EGFR	in vitro	[14]
Breast	MCF-10A 4T1 MCF-7	Suppression of cancer cell growth through C/EBPβ- and PPARγ-mediated lipoapoptosis inhibits human breast cancer cell proliferation and increases the expression of C/EBPβ, PPARγ, adipsin D and perilipin induces adipogenic differentiation, apoptosis and lipoapoptosis of cancer cells	in vitro in vivo	[65]
Breast	MCF-10A MCF-7 MDA-MB231	Apoptosis induction The apoptosis marker proteins, cleaved caspase-3 and caspase-9 were consistently upregulated suppresses the expression of the anti-apoptotic Survivin and induces pro-apoptotic Bax expression	in vitro	[51]
Brain	U87 GI-1 HCN-1A	Morusin-loaded nanoparticles for targeted glioblastoma therapy Morusin was loaded in chlorotoxin-modified PLGA nanoparticles which target chloride channels and MMP-2 in glioma tumor cells Morusin-loaded nanoparticles inhibit growth of U87 and GI-1 glioma cells by ROS generation, enhanced caspase activity, cytoskeletal destabilization and inhibition of MMP activity	in vitro	[89]
Brain	WJ1 WJ2	Inhibition of glioblastoma stem cell growth through stemness attenuation, adipocyte transdifferentiation increases adipogenic markers, such as PPARγ, adipsin D, aP2 and perilipin and induces apoptosis reduces stemness of GSCs by inhibition of the expression of stemness markers (CD133, nestin, Sox2 and Oct4)	in vitro in vivo	[39]
Brain	U251MG LN18 U87MG	TRAIL sensitization by regulating EGFR and DR5 in human glioblastoma cells Combinatorial treatment of TRAIL with morusin synergistically decreased cell viability and increased apoptosis induces the expression of DR5 and decreases anti-apoptotic survivin and XIAP by reduced expression of EGFR and pSTAT3	in vitro	[38]
Skin	JB6 P+	Blocking TPA-induced malignant transformation of mouse epidermal cells reduces the TPA-induced ROS production, AP1 and NF-κB in JB6 P+ cells at non-cytotoxic concentration decreases TPA-upregulation of COX-2, N-cadherin and Vimentin	in vitro	[45]
Stomach	MKN45 SGC7901	Inhibition of cell proliferation and tumor growth by down-regulating c-Myc suppresses tumor growth and down-regulates CDKs and cyclins, such as CDK2, CDK4, cyclin D1 and cyclin E1. reduces the expression of c-Myc and c-Myc protein binding at the E-Box regions	in vitro in vivo	[90]
Pancreas	AsPC-1 BxPC-3 MIAPaCa-2 PANC-1	Apoptosis induction and inhibition of invasion by blockage of STAT3 signaling pathway inhibits STAT3 activation and suppresses activation of upstream JAK1, JAK2 and c-Src kinases. arrest cell cycle at G1/G0 or G2/M phase and causes induction of apoptosis and loss of mitochondrial membrane potential	in vitro	[48]
Bone	U2OS HOS	Inhibition of human osteosarcoma via PI3K-AKT signaling pathway promotes apoptosis and reduces the migration and invasion of osteosarcoma inhibits the PI3K/AKT signaling pathway and induces the expression of caspase-3 and caspase-8	in vitro	[55]
Ovary	A2780 SKOV-3 HO-8910	Paraptosis-like cell death induction through mitochondrial calcium overload and dysfunction causes mitochondrial Ca2+ influx and induces paraptosis-like cell death via mitochondrial Ca2+ overload increases ROS and decreases mitochondrial membrane potential and inhibits the growth of SKOV-3 xenograft in nude mice	in vitro in vivo	[37]
Prostate	DU145 PC-3 LNCaP RWPE-1	Cell death induction through inactivating STAT3 signaling reduces STAT3 activity by suppressing kinase activities of JAK2 and Src and increases SHP1 phosphatase activity down-regulates the expression of STAT3 target genes encoding Bcl-xL, Bcl-2, Survivin, c-Myc and cyclin D1	in vitro	[36]
Cervix	HeLa	Apoptosis induction & inhibition of human cervical cancer stem cell growth and migration through attenuation of NF-κB activity decreases the proliferation, tumor sphere formation and migration of human cervical CSCs and increases apoptosis decreases the expression levels of NF-κB/p65 and Bcl-2, while increases expression levels of Bax and caspase-3	in vitro	[40]
Kidney	769-P 786-O OSRC-2	Anti-cancer activity by disturbing MAPK signaling pathways inhibits cell growth and migration, induces cell apoptosis and induces the cell cycle arrest in the G1 phase up-regulates P-p38 and P-JNK levels, while the down-regulates P-ERK level	in vitro in vivo	[54]
Liver Spleen	H22	Inhibition of transplanted H22 hepatocarcinoma inhibits the tumor growth of transplanted H22 hepatocarcinoma in mice by reducing the expression of NF-κB increases the expression of p53, Survivin, cyclin B1 and caspase-3	in vitro in vivo	[46]
Colon Liver Breast	HT-29 Hep3B MCF-7	Apoptosis induction & suppression of NF-κB activity inhibits the phosphorylation of IKK-α, IKK-β and IκB-α and suppresses NF-κB nuclear localization and its DNA binding causes activation of caspase-8, change of mitochondrial membrane potential, release of Cytochrome c and Smac/DIABLO and activation of caspase-9 and caspase-3	in vitro	[35]
Cervix Breast Bone	HeLa U2OS ZR75B	Attenuation of RACK1-mediated apoptotic cell death by stress granule (SG) formation induces activation of PKR and subsequent eIF2α phosphorylation for SG formation sequestration of RACK1 within the SGs contributes to protection of cells from cell death	in vitro	[74]
Cervix Breast Bone Colon	HeLa MCF-7 U2OS HCT116	Autophagy induction inhibits cell death induces AMPK activation and inhibits mTOR activity, resulting in LC3-II accumulation and ULK1 activation for autophagy autophagy induction is an impediment for morusin-induced apoptosis	in vitro	[68]