Clinical trials have shown that antioxidant supplementation increased the risk of lung and skin cancers, but the underlying molecular mechanism is unknown. Here, we show that epigallocatechin gallate (EGCG) as an exemplary antioxidant induced significant death and DNA damage in human lung and skin normal cells through a reductive mechanism. Our results show direct evidence of reductive DNA damage in the cells. We found that EGCG was much more toxic against normal cells than H2O2 and cisplatin as toxic and cancer-causing agents, while EGCG at low concentrations (≤100 μM) increased slightly the lung cancer cell viability. EGCG induced DNA double-strand breaks and apoptosis in normal cells and enhanced the mutation frequency. These results provide a compelling explanation for the clinical results and unravel a new reductive damaging mechanism in cellular processes. This study therefore provides a fresh understanding of aging and diseases, and may lead to effective prevention and therapies.

Based on a molecular-mechanism-based anticancer drug discovery program enabled by an innovative femtomedicine approach, we have found a previously unknown class of non-platinum-based halogenated molecules (called FMD compounds) as potent antitumor agents for effective treatment of cancers. Here, we present in vitro and in vivo studies of the compounds for targeted chemotherapy of cervical, breast, ovarian, and lung cancers. Our results show that these FMD agents led to DNA damage, cell cycle arrest in the S phase, and apoptosis in cancer cells. We also observed that such a FMD compound caused an increase of reduced glutathione (GSH, an endogenous antioxidant) levels in human normal cells, while it largely depleted GSH in cancer cells. We correspondingly found that these FMD agents exhibited no or little toxicity toward normal cells/tissues, while causing significant cytotoxicity against cancer cells, as well as suppression and delay in tumor growth in mouse xenograft models of cervical, ovarian, breast and lung cancers. These compounds are therefore a previously undiscovered class of potent antitumor agents that can be translated into clinical trials for natural targeted chemotherapy of multiple cancers.

The success of subunit vaccines has been hampered by the problems of weak or short-term immunity and the lack of availability of nontoxic, potent adjuvants. It would be desirable to develop safe and efficient adjuvants with the aim of improving the cellular immune response against the target antigen. In this study, the targeting and sustained release of simple nanoliposomes containing Lycium barbarum polysaccharides (LBP) as an efficacious immune adjuvant to improve immune responses were explored. LBP liposome (LBPL) with high entrapment efficiency (86%) were obtained using a reverse-phase evaporation method and then used to encapsulate the model antigen, ovalbumin (OVA). We demonstrated that the as-synthesized liposome loaded with OVA and LBP (LBPL-OVA) was stable for 45 days and determined the encapsulation stability of OVA at 4°C and 37°C and the release profile of OVA from LBPL-OVA was investigated in pH 7.4 and pH 5.0. Further in vivo investigation showed that the antigen-specific humoral response was correlated with antigen delivery to the draining lymph nodes. The LBPL-OVA were also associated with high levels of uptake by key dendritic cells in the draining lymph nodes and they efficiently stimulated CD4 + and CD8 + T cell proliferation in vivo, further promoting antibody production. These features together elicited a significant humoral and celluar immune response, which was superior to that produced by free antigen alone.

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There is a compelling need to develop anticancer therapies that target cancer cells and tissues. Arising from innovative femtomedicine studies, a new class of non-platinum-based halogenated molecules (called FMD molecules) that selectively kill cancer cells and protect normal cells in treatments of multiple cancers has been discovered. This article reports the first observation of the radiosensitizing effects of such compounds in combination with ionizing radiation for targeted radiotherapy of a variety of cancers. We present in vitro and in vivo studies focused on combination with radiotherapy of cervical, ovarian, head and neck, and lung cancers. Our results demonstrate that treatments of various cancer