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Mychonastessp. 247 is a newly isolated freshwater microalga. Mychonastessp. 247 methanolic extract (ME) suppresses the growth of A549 human non-small-cell lung cancer (NSCLC) cells. However, the underlying mechanism of this anticancer effect remains unclear. The present study aimed to reveal the underlying mechanism of the anticancer effect of ME in A549 cells. The components of ME, their cytotoxicity in normal cells, and their inhibitory effect on the growth and migration of two-dimensional and three-dimensional cultured cancer cells were investigated. We also showed that ME upregulated the mRNA levels of signaling receptors and transporters of retinol (STRA6) and cytochrome P450 family 26 subfamily B member 1, and increased the protein expression of phosphorylated c-Jun N-terminal kinase, B-cell lymphoma protein 2/(Bcl-2)-associated X (Bcl-2/Bax), and cleaved caspase-3. Moreover, co-treatment with N-acetyl-L-cysteine reversed the ME-induced changes in the levels of STRA6 and reactive oxygen species (ROS), confirming their role in the ME-mediated anticancer effect. To the best of our knowledge, this is the first study elucidating the pathway by which ME induces anticancer effects in lung cancer cells. Our results reveal that ME induces NSCLC apoptosis by regulating ROS levels via the STRA6 pathway, suggesting ME as a prospective anticancer agent for lung cancer treatment.

The ubiquitous transcription factor, NF-κB, has been reported to inhibit apoptosis and induce drug resistance in cancer cells. Cordyceps militarisextract (CME) is involved in the regulation of the NF-κB signaling pathway. However, the detailed role of CME in the suppression of the NF-κB signaling pathway is unclear. We found that CME dose-dependently inhibited tumor necrosis factor-α (TNF-α)-induced NF-κB activation in TK-10 human renal cell carcinoma. CME prevented NF-κB from translocating to the nucleus, which resulted in the downregulation of GADD45B, upregulation of MKK7, and phosphorylation of JNK (p-JNK). The increased activation of Bax led to pronounced CME-induced apoptosis, which occurred through caspase-3. Furthermore, the siRNA-mediated knockdown of GADD45B inhibited MKK7 expression, whereas the siRNA-mediated inhibition of MKK7 downregulated p-JNK and the JNK inhibitor, SP600125, inhibited Bax expression. Thus, these results indicated that CME inhibited the activation of GADD45B via the inhibition of NF-κB activation, which upregulated the MKK7-JNK signaling pathway to induce apoptosis in TK-10 cells. Thus, this study reveals a novel anticancer function of CME.