Abstract
A large number of current chemotherapeutic agents prevent the growth of tumors by inhibiting DNA synthesis of cancer cells. It has been found recently that many planar polycyclic aromatic hydrocarbons (PAHs) derivatives, previously known as carcinogenic, display anticancer activity through DNA cross‐linking. However, the practical use of these PAHs is substantially limited by their low therapeutic efficiency and selectivity toward most tumors. Herein, the anticancer property of a nonplanar PAH named [4]helicenium, which exhibits highly selective cytotoxicity toward liver, lung cancer, and leukemia cells compared with normal cells, is reported. Moreover, [4]helicenium effectively inhibits tumor growth in liver cancer‐bearing mice and shows little side effects in normal mice. RNA sequencing and confirmatory results demonstrate that [4]helicenium induces more DNA damage in tumor cells than in normal cells, resulting in tumor cell cycle arrest and apoptosis increment. This study reveals an unexpected role and molecular mechanism for PAHs in selectively killing tumor cells and provides an effective strategy for precision cancer therapies.
Highlights
polycyclic aromatic hydrocarbons (PAHs), they possess a planar π-conjugated structure and can interact with DNA by inserting into the base pairs as intercalatorCancer is a worldwide public health problem and ranks top 2 in or binding to the grooves of DNA due to their hydrophobicity
These results suggest that inducing DNA interstrand crosslinks (ICLs) is the major role of [4]helicenium in hepatocellular carcinoma (HCC) cells, leading to fatal DNA double-strand breaks (DSBs) and cell death
We have explored the biological activity of nonplanar PAH [4]helicenium and demonstrated that [4]helicenium selectively kills cancer cells and inhibits tumor growth in liver cancer-bearing mice without obvious toxic side effects on normal cells and mice
Summary
PAHs, they possess a planar π-conjugated structure and can interact with DNA by inserting into the base pairs as intercalator. Cancer is a worldwide public health problem and ranks top 2 in or binding to the grooves of DNA due to their hydrophobicity. It leading causes of death in this century.[1]. Based on the similar property of binding to DNA, some PAHs such as substituted anthracene[12] and pyrene ring systems have exhibited an anticancer efficiency and been used clinically to treat several leukemias and some solid tumors.[12a,13] the biological functions of PAHs derivatives as carcinogens or anticancer agents might highly depend on their molecular skeletons and substitutions.[14]. We synthesized a nonplanar PAH ([4]helicenium), which possesses good solubility in water and can efficiently bind to DNA. This study first provides evidence that the conversion of planar PAHs into nonplanar PAHs enhances antitumor capability without significant side effects on normal cells
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