Exploration of Targeted Anti-tumor Therapy

Table 1. Details of the anticancer efficacy of BD in several human malignancies using in vitro models

Cancer type	Cell lines	Anti-cancer efficacy	Mode of action	Concentration (μM)	IC₅₀ (anti-proliferation)	References
NSCLC	A549 NCI-H292	Anti-proliferative	↑ROS, ↑pJNK, ↑Apoptosis; ↑LC3-II, ↑Autophagy	0–40	A549: 17.89 (48 h) NCI-H292: 14.42 (48 h)	[28]
NSCLC	A549 H460 PC9 H1975	Anti-proliferative	A549, H460: ↑pJNK, ↓Bcl-2, ↑BAX, ↑caspase 3 and PARP, ↑Apoptosis	0–12.5	A549: 0.6 (48 h) H460: 0.5 (48 h) PC9: 1.0 (48 h) H1975: 2.7 (48 h)	[41]
Pancreatic adenocarcinoma	PANC1 SW1990 CAPAN-1	Anti-proliferative	PANC1: ↑p38-MAPK, ↓Bcl-2, ↑BAX, ↑caspase 3 and 8	< 0.1–> 30	PANC1: 2.53 (72 h) SW1990: 5.21 (72 h) CAPAN-1: 1.35 (72 h)	[29, 37]
Chronic Myeloid Leukemia	K562	Anti-proliferative	↓pAKT and pERK; ↓Ψm, ↑caspase 3 and 9, ↑PARP	0–12	6.37 ± 0.39 (72 h)	[44]
TNBC	MDA-MB-231	Anti-proliferative Anti-invasive Anti-migration	↓PI3K, ↓pAKT, ↑E-cadherins, ↓vimentin and β-catenin, partial EMT reversal	0–100	5.84 (48 h); 2.364 (72 h)	[30]
Osteosarcoma	MNNG/HOS U-2OS MG-63 Saos-2	Anti-proliferative Anti-invasive Anti-migration Anti-CLC	↓pSTAT3, ↓Cyclin D1, CDK4, CDK2, ↑Apoptosis; ↓pSTAT3, ↓CD133, SOX2, Oct-4, Nanog	0–20	MNNG/HOS: 0.9 (48 h) U-2OS: 0.05 (48 h) MG-63: 0.65 (48 h) Saos-2: 0.51 (48 h)	[47]
Hepatocellular carcinoma	Huh7 Hep3B	Anti-proliferative	↑Proteasome, ↓Total β-catenin, ↓Active β-catenin, ↓JAG1, ↓NICD, ↑Apoptosis	0–20	Approx. 2.5 (48 h)	[45]
Hepatocellular carcinoma	Bel7404 HepG2 Hep3B Huh7 PLC	Anti-proliferative	↓miR-95, ↑CUGBP2, ↑Apoptosis	0.25–1.5	Bal7407: ~1.0 (72 h) HepG2: ~0.8 (72 h) Hep3B: ~0.75 (72 h) Huh7: ~0.6 (72 h) PLC: ~0.8 (72 h)	[46]

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Ψm: mitochondrial membrane potential; CD133: prominin-1; CDK2: cyclin dependent kinase 2; CUGBP2: Elav-like family member 2; JAG1: Jagged1; LC3-II: autophagy marker; Nanog: homeobox protein NANOG; NICD: cleaved intracellular domain of Notch receptor; Oct-4: octamer-binding transcription factor 4 (also known as POU5F1); PARP: poly (ADP-ribose) polymerase; p38-MAPK: p38 mitogen-activated protein kinases; pAKT: phosphorylated protein kinase B; pERK: phosphorylated extracellular signal regulated kinase; pJNK: phosphorylated c-Jun N-terminal kinase; pSTAT3: phosphorylated signal transducer and activator of transcription 3; SOX2: SRY (sex determining region Y)-box 2; CDK4: cyclin-dependent kinase 4; EMT: epithelial-mesenchymal transition; miR-95: microRNA-95

Declarations

Author contributions

The concept and design of this manuscript are conceived by ZWS and MG. ZWS, AKP, and MG wrote and revised the manuscript, presented the concept, created figures, tables. All authors have read the manuscript and agreed to the published version of the manuscript.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

This work was supported by the Department of Biotechnology (DBT), under its Ramalingaswami Fellowship number BT/RLF/Re-entry/24/2014 and Science and Engineering Research Board under its ECRA scheme (SERB File No. ECR/2016/001519) award to Dr. Manoj Garg. The sponsor(s) have no role in designing, analysis, interpretation and writing.

Copyright

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