Molecular targets of ivermectin as a potential repurposed drug in cancer therapy: A scoping review

Table 3 Summary of in vitro efficacy outcomes of ivermectin-drug interaction

In-vitro cell lines in study	Drug(s) co-administered with ivermectin	Primary outcomes
Ovarian cancer	Pitavastatin	Synergy: Potentiating pitavastatin’s apoptotic effects and reduced cell viability
Urothelial carcinoma	Z-VAD-FMK (pan-caspase inhibitor)	Inhibited ivermectin-induced apoptosis, confirming Ivermectin’s caspase dependence
		Enhanced ivermectin’s apoptotic effect
	SP600125 (JNK inhibitor)	Reduced cell viability
	PD98059 (ERK inhibitor)	No synergistic effect
High-grade serous carcinoma	Paclitaxel	Synergy: Augmenting paclitaxel-induced cytotoxicity and apoptosis, with decreased cell viability
Human cholangiocarcinoma	Gemcitabine	Apoptosis induction in gemcitabine-resistant cells through S-phase arrest and inhibition of proliferation
		Suppression of colony formation
Human pancreatic cancer	rMETase	Synergistic: Reduced cell viability by about 80% compared to about 45% using ivermectin alone and about 37% using rMETase alone
Human breast cancer	Tamoxifen	Pharmacodynamic synergy: Lower doses of tamoxifen were required to inhibit proliferation in resistant cell lines through reduced expression of snail, vimentin, LRP6, and Wnt5a/b on western blot assay
Human CML	Flumatinib	Increased apoptosis
		Increased autophagic flux in flumatinib-resistant CML
Melanoma	Bafilomycin A1, acetyl cysteine (autophagy inhibitors)	Enhanced ivermectin-induced autophagy
Breast cancer(majorly), but also melanoma, colon adenocarcinoma, pancreatic cancer, head and neck cancer, leukemia, and prostate cancer	Doxorubicin, paclitaxel	Rapid synergistic toxicity to cancer cells
Human neuroblastoma	Cyclosporin A (MDR1 inhibitor), MK571 (MRP inhibitor), Ko143 (BCRP inhibitor, negative control)	High-affinity inhibition of MDR1
		Moderate inhibition of MRP
Human cancer cell lines	Tamoxifen, paclitaxel, cisplatin, erlotinib, cetuximab, dasatinib, daunorubicin, cytarabine, docetaxel	Synergistic effects via enhanced apoptosis, reversal of drug resistance, and inhibition of multi-drug resistance proteins

BCRP: Breast cancer resistance protein; CML: Chronic myeloid leukemia; ERK: Extracellular signal-regulated kinase; JNK: C-Jun N-terminal kinase; Ko143: CAS 461054-93-3; LRP6: Low-density lipoprotein receptor-related protein 6; MDR1: P-glycoprotein inhibitors MK-571 (L-660711); MRP: Multidrug resistance-associated protein; rMETase: Recombinant methioninase; Z-VAD-FMK: Carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone.