Hepatotoxic mechanism of cantharidin: insights and strategies for therapeutic intervention

Abstract

Cantharidin (CTD), a natural compound derived from Mylabris, is widely used in traditional Oriental medicine for its potent anticancer properties. However, its clinical application is restricted due to its high toxicity, particularly towards the liver. This review provides a concise understanding of the hepatotoxic mechanisms of CTD and highlights novel therapeutic strategies to mitigate its toxicity while enhancing its anticancer efficacy. We systematically explore the molecular mechanisms underlying CTD-induced hepatotoxicity, focusing on the involvement of apoptotic and autophagic processes in hepatocyte injury. We further discuss the endogenous and exogenous pathways implicated in CTD-induced liver damage and potential therapeutic targets. This review also summarizes the structural modifications of CTD derivatives and their impact on anticancer activity. Additionally, we delve into the advancements in nanoparticle-based drug delivery systems that hold promise in overcoming the limitations of CTD derivatives. By offering valuable insights into the hepatotoxic mechanisms of CTD and outlining potential avenues for future research, this review contributes to the ongoing efforts to develop safer and more effective CTD-based therapies.

Aconitine and its derivatives: bioactivities, structure-activity relationships and preliminary molecular mechanisms

“…Specifically, the antagonistic impact of AC on taste bud tissue biosensors was investigated through in vitro studies. As shown in Figure 10 , the findings demonstrated that AC, acting as a mixed allosteric regulatory ligand of capsaicin, potentially triggers intracellular G protein/PI3K/PIP2 signaling pathways by binding to CB1 and CB2 ( Jin et al, 2023 ). Consequently, this interaction ultimately leads to an augmentation in intracellular phosphatidylinositol 4,5-bisphosphate (PIP2) levels, consequently inducing the closure of the TRPV1 channel and the manifestation of analgesic effects.…”

“…The IC 50 values for 24o were determined to be 7.58 μM and 7.02 μM for MCF-7 and MCF-7/ADR cells, respectively. Additionally, in vitro assays revealed that 24o induced cytotoxicity in MCF-7/ADR cells by arresting the cell cycle at the G0/G1 phase ( Jin et al, 2023 ). As shown in Scheme 2 , the aforementioned research group successfully identified a range of structurally diverse derivatives of AC by implementing modifications on the A-ring, C-ring, D-ring, and N-atom of the AC skeleton ( Zhang et al, 2023 ).…”

A Comprehensive Review of Various Therapeutic Strategies for the Management of Skin Cancer

“…Cantharidin is a poisonous monoterpene obtained from blister beetles that belong to the order Coleoptera and family Meloidae . It can be used to treat various types of cancer like hepatic cancer, leukemia, breast cancer, and other diseases . It was found that it suppresses the MAPK (p38, JNK, and ERK) signaling pathway via decreasing NF-κB and AKT, resulting in down-regulation of MMP-2/-9 and uPA protein expression in SC cells…”