Table 1 Overview of clotrimazole's antitumor effects in different types of cancer.

From: Clotrimazole inhibits growth of multiple myeloma cells in vitro via G0/G1 arrest and mitochondrial apoptosis

Author(s), year and refs

Cancer type

Cancer cell lines

Main findings

Mechanism of action

Dosage and administration

Conclusion

Liu et al. 202213

Hepatocellular carcinoma

MHCC-97H, SMCC 7721, Hep3B, HuH7

Clotrimazole inhibits HCC cell migration and invasion

Inhibition of ERK phosphorylation and EMT

20 μM clotrimazole in HCC cells

Clotrimazole inhibits HCC metastasis through the suppression of EMT via the ERK pathway

Ochioni et al. 202114

Melanoma

B16F10

Clotrimazole inhibits tumor growth, reduces lactate levels in the tumor microenvironment, and decreases vascular endothelial growth factor expression

Inhibition of the PI3K pathway, reduction of glycolysis, and repolarization of tumor-associated macrophages cells

200 mg/kg/day in vivo

Clotrimazole exerts anticancer effects by modulating the tumor microenvironment and TAM polarization

Bae et al. 201815

Breast cancer

MCF-7, MDA-MB-231

Clotrimazole inhibited cell proliferation and invasiveness of breast cancer cells

Induction of apoptosis, G1 phase arrest, inhibition of MMP9

50 μM clotrimazole in breast cancer cells; 100 mg/kg/day in vivo

Clotrimazole shows strong antitumor activity. It has the potential to be repositioned as a cancer therapy

Wang et al. 201416

Oral squamous cell carcinoma

CAL27, SCC25, UM1

Clotrimazole inhibited cell viability, colony formation, induced apoptosis, and reduced tumor growth

Induction of G0/G1 cell cycle arrest, down-regulation of Bcl-2, up-regulation of Bax

40 μM clotrimazole in vitro; 150 mg/kg/day in vivo

Clotrimazole shows potential as a therapeutic agent for OSCC by inducing apoptosis and inhibiting cell proliferation

Adinolfi et al. 201532

Melanoma

A375

Clotrimazole induces cytotoxicity in A375 human melanoma cells, induces cell cycle arrest at the G1-S phase transition, and alters membrane-bound protein V responsiveness

Inhibits hexokinase, induces cell cycle arrest, induces apoptosis

10 μM Clotrimazole in A375 Cells

Clotrimazole has a pro-apoptotic effect on melanoma cells

Zuccolini et al. 202333

Melanoma, pancreatic cancer

WM266-4, Panc-1

Clotrimazole causes a decrease in cell viability and migration in WM266-4 and Panc-1 cells, independent of IK expression levels

IK Independence effect

30 μM Clotrimazole in WM266-4 Cells

The effect of clotrimazole on cancer cells may be due to off-target effects on other cellular targets or blockade of IK channels located in intracellular organelles

  1. ERK Extracellular signal-regulated kinase, EMT Epithelial–mesenchymal transition, PI3K Phosphoinositide 3-kinase, TAM Tumor-associated macrophages, MMP Matrix metalloproteinase, IK Inwardly rectifying potassium channels, OSCC Oral squamous cell carcinoma.