Since the incidence of cancer has been on the rise due to increasing exposure to various carcinogenic factors in recent years, cancer has gradually become the first killer to the health of human beings. A growing attention has been paid to anti-cancer effects of traditional Chinese medicine (TCM) with low toxicity and good efficacy. As a kind of TCM, Periplaneta americana (P. americana) has a good effect on clinical application, and its anti-tumor effects has been increasingly well studied. In this review, the research progress on the anti-tumor effects of P. americana was summarized. The main mechanisms of its anti-tumor effects include suppression of tumor cell growth, induction of cell cycle arrest and tumor cell apoptosis, inhibition of angiogenesis, enhancement of immunity, and reversal of tumor drug resistance. This review aims to provide an overview of the research on anti-tumor effects of P. americana and aids in its further application as an anti-tumor drug.

Cardamonin is a chalcone that presents at high content in the seeds of Alpinia katsumadai Hayata. In recent decades, researchers have found that it is not only an edible spice, but also a remarkable herb with a wide range of pharmacological properties. However, its specific metabolic routes in vivo remain unclear while these metabolites may accumulate to exert pharmacological effects. Our study aimed to clarify the metabolic pathways of cardamonin after oral administration to rats. Here, an advanced UHPLC-Q-Exactive Orbitrap MS analytical technique was applied for efficient detection of metabolites in vivo, which especially showed benefits in obtainment of the fragment ions with relatively lower contents. We also established a novel strategy to identify metabolites based on typical fragmentation routes. The results indicated that a total of 40 metabolites could be categorized into 3 types with consideration of the particular structures and characteristic fragment ions. Then, diagnostic product ions (DPIs) of each type were summarized for further screening and identification of metabolites derived from cardamonin. Finally, methylation, demethylation, hydrogenation, hydroxylation, dehydroxylation, glucuronidation and sulfation were confirmed to be the major metabolic pathways in vivo. Our observation extended the metabolic mechanism of cardamonin and could be of great benefits to interpreting the action mechanism of cardamonin in vivo.

Background: Primary liver cancer is the sixth most commonly diagnosed cancer and the third most common cause of cancer death worldwide. Chansu is made by processing and drying the white serous fluid of the posterior ear and skin glands of Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider. Chansu is a well-known traditional Chinese medicine (TCM) that is mainly used for detoxification, detumescence, analgesia, the treatment of cancer, and heart failure. Cinobufagin, as a bufadienolide, has been reported as the main antitumor active component of Chansu. However, the molecular mechanisms related to the anticancer effects of cinobufagin still remain elusive. Purpose: The purpose of this study is to explore whether cinobufagin inhibits the growth of HepG2 and SK-HEP-1 tumor cells by inducing peroxisome dysfunction and interfering with lipid metabolism. Methods: The protein levels of catalase, ABCD3, PEX5, PEX6, and PEX10 in human hepatoma cells were analyzed by Western blotting. The effects of cinobufagin on the viability of HepG2 and SK-HEP-1 cells were detected by cell counting kit-8 (CCK-8) assay and clone formation assay. Small interfering RNA (siRNA) transfection was used to explore whether inhibition of PEX could enhance the inhibitory effect of cinobufagin on cell growth of HepG2 and SK-HEP-1 tumor cells. The effects of cinobufagin on lipid metabolism were analyzed by untargeted metabolomics. The in vivo antitumor effects of cinobufagin were verified by animal studies. Results: Cinobufagin causes peroxisome dysfunction in HepG2 and SK-HEP-1 tumor cells. From a mechanistic point of view, we reveal that cinobufagin downregulates the expression of PEX5, PEX10, and PEX6. In addition, through RNA interference, cinobufagin partially blocks the growth of HepG2 and SK-HEP-1 tumor cells and restrains the expression of lipid metabolism-related proteins via downregulating the expression of PEX5 and PEX10. Subsequently, we perform a non-targeted metabolomics analysis of the cells and find that cinobufagin exerts its anti-hepatoma effects by interfering with lipid metabolic reprogramming. The results show that cinobufagin mainly interferes with glycerophospholipid and fatty acyl levels. In addition, in vivo experiments reveal that cinobufagin restrains tumor growth without obvious adverse effects. Serum metabolomics analyses reveal that cinobufagin causes significant changes in the levels of lipid and lipid-like differential metabolites. Conclusion: Cinobufagin is a promising natural drug for the treatment of liver cancer, and PEXs may be potential molecular targets of cinobufagin to exert anticancer effects. Cinobufagin induces peroxisome dysfunction through suppression of the proteins encoded by the PEX genes and interferes with lipid metabolism to restrain the growth of liver cancer cells.