Mutations in the mitochondrial genome confer resistance of cancer cells to anticancer drugs.

The majority of cancer cells harbor homoplasmic somatic mutations in the mitochondrial genome. We show here that mutations in mitochondrial DNA (mtDNA) are responsible for anticancer drug tolerance. We constructed several trans-mitochondrial hybrids (cybrids) with mtDNA derived from human pancreas cancer cell lines CFPAC-1 and CAPAN-2 as well as from healthy individuals.

Biological gain of carbon-ion radiotherapy for the early response of tumor growth delay and against early response of skin reaction in mice.

The biological effectiveness of carbon ions relative to gamma rays (RBE) was compared between the tumor growth delay and an early skin reaction of syngeneic mice. The RBE was larger for a tumor than skin when irradiated with large doses of high-LET (linear energy transfer) carbon ions. The intra-track damage (a term of a linear quadratic model) of a tumor and skin increased equally with an increase of the LET, while the inter-track damage (beta term) of skin alone increased with the LET.

Apoptosis of human melanoma cells by a combination of lonidamine and radiation.

Human melanoma is the most aggressive form of human skin cancer, and is notoriously resistant to any current modalities of cancer therapy. Here we show that lonidamine (LND), a mitochondria-targeting non-conventional chemotherapeutic agent, markedly induced apoptosis in radioresistant human malignant melanoma C32TG cells. Either LND of up to 250 microM or X-ray irradiation of up to 15 Gy alone induced only a few percent of the apoptosis when administrated separately.