Su Hwan Park, M.S., Juheon Lee, M.S., Hye Jin Yun, B.S., Seok-Ho Kim, Ph.D., and Jong-Ho Lee, Ph.D.. Ann Lab Med -0001;0:. https://doi.org/10.3343/alm.2023.0443

Black soybeans have numerous health benefits owing to their high polyphenolic content, antioxidant activity, and antitumor effects. We previously reported that the Korean black soybean cultivar ‘Soman’ possesses higher anthocyanin and isoflavone contents and superior antioxidant potential than other Korean black soybean cultivars and landraces (Seoritae) do. Here, we investigated and compared the antitumor effects of Soman and Seoritae and aimed to elucidate the possible mechanisms of action. Soman inhibited cancer cell proliferation and was more potent than Seoritae. Mechanistically, Soman inhibited the phosphorylation of the signal transducer and activator of transcription (STAT1, 3, and 5) in a reactive oxygen species (ROS)-independent manner, subsequently decreasing glycolytic enzyme expression and the activities of pyruvate kinase and lactate dehydrogenase. Thus, Soman suppressed glucose uptake, lactate production, and ATP production in cancer cells. Additionally, it inhibited tumor growth in a B16F10 murine melanoma syngeneic model, accompanied by reduced STAT1 phosphorylation and decreased proliferation in Soman-treated mice, more potently than observed in Seoritae-treated mice. These findings showed that Soman exerted superior antitumor activities by suppressing STAT-mediated aerobic glycolysis and proliferation. Overall, our findings demonstrate the potent, tumor-suppressive role of Soman in human cancer and uncover a novel molecular mechanism for its therapeutic effects in cancer treatment.

Insecticides have been applied in various household products, and our previous study showed that hydramethylnon (HM), among five classes tested, showed significant pulmonary toxicity in rats and human A549 cells. In this study, we investigated the underlying molecular mechanisms of HM-induced toxicity in human bronchial epithelial cells (HBECs) using BEAS-2B and 16HBE14o cells. In addition, these mechanisms were further confirmed in mice using an intratracheal instillation model. HM treatment induced cytotoxicity in both cell lines, characterized by cell cycle arrest, inhibition of cell proliferation, and cell death with apoptotic features. Notably, HM treatment triggered a rapid increase in necroptosis signaling, as evidenced by phosphorylation of receptor-interacting protein kinase (RIPK) 1 and mixed lineage kinase domain-like (MLKL), and subsequent necroptosis signaling at mitochondria. This activation disrupted mitochondrial homeostasis as evidenced by a reduction in mitochondrial content, as assessed by decreased translocase of outer mitochondrial membrane 20 (TOM20) fluorescence intensity, loss of mitochondrial DNA, reduced electron transport chain complex proteins, adenosine triphosphate (ATP) depletion, increased reactive oxygen species (ROS), and induction of mitophagy. This necroptosis-associated mitochondrial dysfunction ultimately resulted in cell death with apoptotic features of HBECs. Consistently, intratracheal instillation of HM in mice induced acute lung injury with pronounced necroptosis signaling, mitochondrial loss in airway bronchial epithelial cells, and increased cell death with apoptotic features. These findings demonstrate that HM induces cytotoxicity in bronchial epithelial cells associated with necroptosis signaling and mitochondrial dysfunction in vitro and in vivo, revealing a novel mechanism of inhalation toxicity and highlighting the potential risks of HM-containing household products.