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A potential novel treatment strategy for breast cancer: The regulation of apoptosis and metastasis by mitochondria-targeted lupeol-triphenylphosphine derivatives.

Xinyang Liu,Jing Yang,X. Song,Haotian Zhang,Zengxin Wang,Jing Ma,Lina Guo,Xiaohui Du,Hongxia Cui

Published 2025 in Bioorganic chemistry (Print)

ABSTRACT

Lupeol (LP), a pentacyclic triterpenoid compound derived from various plants, exhibits promising antitumor potential. Here, mitochondria-targeted LP derivatives by conjugating LP with triphenylphosphonium (TPP+) were synthesized, and their effects on breast cancer cells were investigated. Exploiting the elevated mitochondrial membrane potential (ΔΨm) in tumor cells compared to normal cells, lupeol-triphenylphosphonium (LP-TPP+) derivatives were designed to enhance tumor cell selectivity. In vitro and in vivo studies demonstrated that LP-TPP+ derivatives potently restricted the viability and proliferation of MDA-MB-231 cells, encompassing apoptosis featured by disrupted ΔΨm, altered expression of apoptosis-related proteins, and enhanced reactive oxygen species (ROS) generation. Notably, LP-TPP+ treatment reduced tumor growth with minimal toxicity, while significantly suppressing cell invasion and metastasis by modulating the expression of invasion-related proteins. These findings highlight the therapeutic potential of LP-TPP+ as a mitochondria-targeted agent for breast cancer, underscoring the utility of combining natural products with mitochondrial-targeting moieties to enhance antitumor selectivity and efficacy.

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