Because of the high incidence of cardiovascular diseases in Asian countries, traditional fermented foods from Asia have been increasingly investigated for antiatherosclerotic effects. This study investigated the production of nattokinase, a serine fibrinolytic enzyme, in pigeon pea by Bacillus subtilis fermentation. B. subtilis 14714, B. subtilis 14715, B. subtilis 14716, and B. subtilis 14718 were employed to produce nattokinase. The highest nattokinase activity in pigeon pea was obtained using B. subtilis 14715 fermentation for 32 hours. In addition, the levels of antioxidants (phenolics and flavonoids) and angiotensin converting enzyme inhibitory activity were increased in B. subtilis 14715-fermented pigeon pea, compared with those in nonfermented pigeon pea. In an animal model, we found that both water extracts of pigeon pea (100 mg/kg body weight) and water extracts of B. subtilis-fermented pigeon pea (100 mg/kg body weight) significantly improved systolic blood pressure (21 mmHg) and diastolic blood pressure (30 mmHg) in spontaneously hypertensive rats. These results suggest that Bacillus-fermented pigeon pea has benefits for cardiovascular health and can be developed as a new dietary supplement or functional food that prevents hypertension.

Extracellular vesicle (EV)-mediated intercellular communication acts as a critical culprit in cancer development. The selective packaging of oncogenic molecules renders tumor-derived EVs capable of altering the tumor microenvironment and thereby modulating cancer developments that may contribute to drug resistance and cancer recurrence. Moreover, the molecular and functional characteristics of cancer through its development and posttreatment evolve over time. Tumor-derived EVs are profoundly involved in this process and can, therefore, provide valuable real-time information to reflect dynamic changes occurring within the body. Because they bear unique molecular profiles or signatures, tumor-derived EVs have been highlighted as valuable diagnostic and predictive biomarkers as well as novel therapeutic targets. In addition, the use of an advanced EV-based drug delivery system for cancer therapeutics has recently been emphasized in both basic and clinical studies. In this review, we highlight comprehensive aspects of tumor-derived EVs in oncogenic processes and their potential clinical applications.

Chemotherapy is the main approach for treating advanced and recurrent carcinoma, but the clinical performance of chemotherapy is limited by relatively low response rates, drug resistance, and adverse effects that severely affect the quality of life of patients. An association between epithelial-mesenchymal transition (EMT) and chemotherapy resistance has been investigated in recent studies. Our recent studies have found that the aqueous extract of Solanum nigrum (AESN) is a crucial ingredient in some traditional Chinese medicine formulas for treating various types of cancer patients and exhibits antitumor effects. We evaluated the suppression of EMT in MCF-7 breast cancer cells treated with AESN. The mitochondrial morphology was investigated using Mitotracker Deep-Red FM stain. Our results indicated that AESN markedly inhibited cell viability of MCF-7 breast cancer cells through apoptosis induction and cell cycle arrest mediated by activation of caspase-3 and production of reactive oxygen species. Furthermore, mitochondrial fission was observed in MCF-7 breast cancer cells treated with AESN. In addition to elevation of E-cadherin, downregulations of ZEB1, N-cadherin, and vimentin were found in AESN-treated MCF-7 breast cancer cells. These results suggested that AESN could inhibit EMT of MCF-7 breast cancer cells mediated by attenuation of mitochondrial function. AESN could be potentially beneficial in treating breast cancer cells, and may be of interest for future studies in developing integrative cancer therapy against proliferation, metastasis, and migration of breast cancer cells.

Pardaxin (H-GFFALIPKIISSPLFKTLLSAVGSALSSSGGQE-OH), a 33-amino-acid polypeptide, is an antimicrobial peptide (AMP) isolated from the marine fish species Pardachirus marmoratus. Pardaxin shows antibacterial and antitumor activities. However, pardaxin-induced inhibition of oral cancer and the mechanism of tumor reduction in buccal pouch carcinogenesis after pardaxin painting remain undetermined. Additionally, the toxic effects of pardaxin on normal tissue remain unclear. The present study investigated the anticancer activity of pardaxin in oral squamous cell carcinoma (OSCC) cells in the hamster buccal pouch model with or without 7,12-dimethylbenz[a]anthracene (DMBA) pretreatment. This is the first study to confirm the effects of pardaxin on normal tissue and its nontoxic effects in vivo. Cell viability assays and colony formation tests in OSCC cell lines (SCC-4) demonstrated that pardaxin reduced cell viability in a dose-dependent manner. Immunofluorescence staining of cleaved caspase-3 in SCC-4 cells revealed that expression of activated caspase-3 in SCC-4 cells significantly increased after 24-h treatment with pardaxin. Additionally, a cell cycle analysis indicated that pardaxin treatment resulted in the cell cycle arrest of SCC-4 cells in the G2/M phase, thereby limiting cell proliferation. Furthermore, pardaxin treatment substantially alleviated carcinogenesis in the DMBA-induced hamster buccal pouch model by lowering prostaglandin E₂ levels. These results suggest that pardaxin is a potential marine drug for adjuvant chemotherapy for human OSCC and oral cancer.

Colorectal cancer is one of the most common cancers worldwide and chemotherapy is the main approach for the treatment of advanced and recurrent cases. Developing an effective complementary therapy could help to improve tumor suppression efficiency and control adverse effects from chemotherapy. Paris polyphylla is a folk medicine for treating various forms of cancer, but its effect on colorectal cancer is largely unexplored. The aim of the present study is to investigate the tumor suppression efficacy and the mechanism of action of the ethanolic extract from P. polyphylla (EEPP) in DLD-1 human colorectal carcinoma cells and to evaluate its combined effect with chemotherapeutic drug doxorubicin. The data indicated that EEPP induced DLD-1 cell death via the upregulation of the autophagy markers, without triggering p53- and caspase-3-dependent apoptosis. Moreover, EEPP treatment in combination with doxorubicin enhanced cytotoxicity in these tumor cells. Pennogenin 3-O-beta-chacotrioside and polyphyllin VI were isolated from EEPP and identified as the main candidate active components. Our results suggest that EEPP deserves further evaluation for development as complementary chemotherapy for colorectal cancer.