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Targeting Lonidamine to Mitochondria Mitigates Lung Tumorigenesis and Brain Metastasis

par webmestre - publié le

Targeting Lonidamine to Mitochondria Mitigates Lung Tumorigenesis and Brain Metastasis

Lung cancer often has a poor prognosis, with brain metastases a major reason for mortality. We modified lonidamine (LND), an antiglycolytic drug with limited efficacy, to mitochondria-targeted mito-lonidamine (Mito-LND) which is 100-fold more potent.

Mito-LND is a tumor selective inhibitor of oxidative phosphorylation, inhibits mitochondrial bioenergetics in lung cancer cells and mitigates lung cancer cell viability, growth, progression, and metastasis of lung cancer xenografts in mice.

Mito-LND blocks lung tumor development and brain metastasis and causes no toxicity in mice even when administered for eight weeks at 50 times the effective cancer inhibitory dose.

We showed that mitochondrial targeting of LND is a promising therapeutic approach for investigating the role of autophagy in mitigating lung cancer development and brain metastasis.

Targeting lonidamine to mitochondria