. 2024 Oct 3;11(1):93. doi: 10.1186/s40643-024-00805-0

Table 4.

In vitro anti-cancer activities of SV and SVPs and their mechanisms of action on human cancer cells

Peptide/venom	Sequence	Dosage	Species origin	Activity	Cancer type	Cell line	Target	Reference
Crude venom	–	Dose dependant manner	A. crassicauda	Proliferation blocking	Human neuroblastoma	SH-SY5Y	Induces apoptosis through increasing nitric oxide production, caspase-3 activity, and depolarizing mitochondrial membrane and arrests S phase	(Zargan et al. 2011a, 2011b; Zargan et al. 2011a, b, c)
Crude venom	–	Dose dependant manner	A. crassicauda	Proliferation blocking	Human breast cancer	MCF-7		(Zargan et al. 2011a, 2011b; Zargan et al. 2011a, b, c)
AcrAP-1 and AcrAP-2 (non-disulfide-bridged peptides) (NDBP), and their high cationic analogs (HC-AcrAP)	FLF KLIP KAI KGLI KAFK FLF KLIP KAI KGLL KAFK	IC₅₀ (0.001-100 µM)	A. crassicauda	HC-AcrAP analogs proliferation blocking (IC50 2–3.6 µM)	Human lung adenocarcinoma. Human breast carcinoma. Human breast tumorigenic. Human prostate carcinoma	H460 MB435s MCF-7 PC-3	(Probably) inducing cell lysis	(Possani et al. 2000)
Bengalin 72 kDa	GPLTILHINDVHAAFEQFNT	IC₅₀ more than 3 (3.5–4) µg/mL	Heterometrus bengalensis koch	Proliferation blocking	Human leukemia	U937 and K562	Increases expression of Bax/Bcl-2 ratio, caspase 3 and 9, reduces mitochondrial membrane potential, heat shock proteins (HSP) 70 and 90	(Gupta et al. 2010; Heather et al. 2016)
Bmk (70-80 kDa)	CGPCFTTDANMARKCRECCGGIGKCFGPQCLCNRI	5. 10 µM	B martensii Karsch	Proliferation blocking	Human leukemia	(THP-1) acute monocytic leukemia cell line	Inhibit the invasion ability of U87 glioma cell	(Song et al. 2012)
AaCTX	MCIPCFTTNPNMAAKCNACCGSRRGS–CRGPQCIC–-	5. 200 µM	Androctonus australis	Inhibition the migration and invasion	Human glioma cells	U87	Inhibit U87 glioma cell migration	(Rjeibi et al. 2011)
Bmk -AGAP 71.42KDa (66 amino acids)	VRDGYIADDKNCGRNAYCDDECEKNGAESGYCQWAGVYGNACWCYKLPDKLPDKVPIRVPGKCNGG	(IC₅₀ = 40 µM for MCF-7 and 50 µM for MDA-MB-231 cells)	B martensii Karsch	Proliferation blocking, stemness, sphere formation, colony formation epithelial-mesenchymal transition, migration, and invasion	Human breast cancer	MCF-7 and MDA-MB-231	Down-regulation of Oct4, SOX2, Nanog, N-cadherin, Snail, and PTX3 and up-regulation of E-cadherin at both gene and protein levels Interference of Na⁺ toxin with P-AKT, NF-kB, Bcl-2, and MAPK signaling pathway	(Kampo et al. 2019)
Crude venom		IC₅₀ (20-100 µg/mL)	A bicolor A crassicauda	Prevents cell motility and colony mitosis	Human breast cancer	MDA-MB-231	Two mechanisms that involved in migration and invasion of cancer cells are proposed a) a decrease in MMPs expression, and b) a reduction in FAK autophosphorylation levels	(Al-Asmari et al. 2016a, b)
Crude venom		IC₅₀ (20-100 µg/mL)	A bicolor A crassicauda	Prevents cell motility and colony mitosis	Human colorectal cancer	HCT-8 and HCT116		(Al-Asmari et al. 2016a, b)
Gonearrestide (P13) (18 amino acids, 2192 Da)	W C Y K L P D R V S I K E K G R C N	IC₅₀ (2-200 µM)	A mauritanicus	Proliferation blocking in dose-dependent	Human colon cancer	HCT116	Arrests cancer cell cycle in the G1 phase via modulating cell cycle checkpoint proteins (down-regulate CDK4, and upregulate cyclin D3, p21, p27)	(Li et al. 2018)
Bmk (50–60) amino acids 65 kDa	VRDAAYIAKPENCVYECGITQDCNKLCTENGAESGYCQW	IC₅₀ (10-200 µg/mL)	B martensii Karsch	Proliferation blocking	Human Prostate cancer	DU145	Upregulation of Bax apoptotic gene expression, and down-regulated of Bcl-2 anti-apoptotic gene expression	(Zhang et al. 2009)
Bmk (50–60) amino acids 65 kDa	VRDAAYIAKPENCVYECGITQDCNKLCTENGAESGYCQW	IC₅₀ (10-200 µg/mL)		Proliferation blocking	Human Prostate cancer	DU145	Inhibiting proliferation by G1/S arresting cancer cells cycle	(Kampo et al. 2019)
Bmk -CT	CGPCFTTDANMARKCRECCGGIGKCFGPQCLCNRI			Migration and invasion blocking	Human glioma	SGH-44	Blocking of Cl⁻¹ ion channel, hence, selectively target glioma	(Hmed et al. 2013; Jian 2014; Pedersen and Stock 2013)
Iberiotoxin (IbTX) (34 amino acids, 36.07 kDa)	GDCLPHLKRCKADNDCCGKKCKRRGTNAEKRCR		Buthus tumulus	Prevents growth and proliferation	Human cervical cancer	HeLa	Blocks calcium-activated potassium channels KCNMA1 (KCa1.1, BK) Found to be expressed in cervical cancer-hormone dependent block large conductance Ca⁺² activated K⁺ (BK) channel	(Han et al. 2007; Ramírez et al. 2018)
					Human ovarian cancer	A2780
					Human breast cancer	MCF-7
Margatoxin (MgTX, 39 amino acids, 41.92 kDa)	TIINVKCTSPKQCLPPCKAQFGQSAGAKCMNGKCKCYPH	Dose dependant manner	C. margartatus	Proliferation blocking	Human lung adenocarcinoma	A549	Blocks Kv1.3 and increases expression level of p21Waf1/Cip1 and decreases the expression level of Cdk4 and cyclin D3	(Jang et al. 2011)
Chlorotoxin (CTX/ or ClTx) (36 amino acids, MW4.02 KDa)	MCMPCFTTDHQMARKCDDCCGGKGRGKCYGPQCLCR	IC₅₀ more than 20 (20–100) µg/mL	L quinquestriatus	Stops migration and invasion	Human glioma	D54-MG and CCF-STTG-1	Specially binds to MMP-2 and modulates active MMP-2 expression and enhance Cl-channel receptors uptake (CIC-3)	(Deshane et al. 2003; McFerrin et al. 2006)
Chlorotoxin (CTX/ or ClTx) (36 amino acids, MW4.02 KDa)	MCMPCFTTDHQMARKCDDCCGGKGRGKCYGPQCLCR	IC₅₀ more than 20 (20–100) µg/mL	L quinquestriatus	prevents cell motility, and colony mitosis	Human breast cancer	MDA-MB-231		(Deshane et al. 2003; McFerrin et al. 2006)
crude venom	–		L quinquestriatus		Human colorectal cancer	HCT-8 and HCT116	Two mechanisms proposed are a) a decrease in the expression of MMPs, and b) a reduction in the phosphorylation levels of FAK, which is involved in cell migration and invasion	(Al-Asmari et al. 2016a, b)
crude venom	–	IC₅₀ (20–100) µg/mL	O doriae	Prevents proliferation and DNA synthesis	Human breast cancer	MCF-7	Depolarizes mitochondria, activates Caspase-3, and depletes antioxidant activities	(Zargan et al. 2011a, b, c)
crude venom	–	IC₅₀ (20–100) µg/mL	O doriae	Prevents proliferation and DNA synthesis	Human neuroblastoma	SH-SY5Y		Zargan et al. 2011a, b, c)
crude venom	–	IC₅₀ (100–1000) µg/mL	R junceus	Proliferation blocking	Different human cancer cell lines	HeLa, SiHa, Hep-2, NCI-H292, A549, MDA-MB-231, MDA-MB-468, HT-29	Increased expression of P53, Bax, Caspase 3, 8, & 9 and reduced Bcl-2 in HeLa (apoptosis > necrosis) whereas reduced expression p53, did not affect Bax but reduced Bcl-2 in A549 (necrosis > apoptosis) reflecting concentration used > IC₅₀ or < IC₅₀	(Mikaelian et al. 2020)
Crude venom		IC₅₀ (500-1000 µg/mL)	A bicolor A crassicauda	Proliferation blocking	Human breast cancer. Human colorectal cancer	MDA-MB-231 HCT	Induces apoptosis more than necrotic death, and arrests cells at G0/G1 phase upregulates p53, downregulates Bcl-xL	(Al-Asmari et al. 2016a, b; Al-Asmari et al. 2016a, b; Al-Asmari et al. 2018a, 2018b)
Neopladine-1 (29.918 kDa) and Neopladine-2 (30.388 kDa)	–	Dose dependant manner	T discrepans	Both peptides induce apoptosis	Human breast carcinoma	SKBR3	Bind to SKBR3 cell surface and trigger FasL and BcL-2 expression	(D’Suze et al. 2010)
TsAp-1 and TsAp-2 (17 amino acids) high cationic TsAP-1 and TsAP-2	ATGCAAATAAAACATCTCATTACTCTCTTCTTTCTCGTCTTGATCGTTGC	Dose dependant manner	T serrulatus	Highly proliferation inhibitors	Human squamous carcinoma lung adenocarcinoma. Human prostate adenocarcinoma Human breast carcinoma. Human glioblastoma	H157 H838 PC-3 MCF-7 U251-MG		(Guo et al. 2013)