Beaveria bassiana (Balsamo) Vuillemin combined with cinnamaldehyde enhances anti-hepatocellular carcinoma effects of T cells by the PGC-1α/DRP1-regulated mitochondrial biogenesis and fission.

Abstract

Ethnopharmacological relevance: Beaveria bassiana (Balsamo) Vuillemin (BEA) and cinnamaldehyde (CA), primarily derived from traditional Chinese medicine (TCM) named Bombyx batryticatus and Cinnamomum cassia, play an immunomodulatory role in different disease.

Aim of the study: Hepatocellular carcinoma (HCC) is a prevalent malignant tumor characterized by immune dysfunction. In this study, we investigated BEA and CA's regulate ability on T cell mitochondrial metabolism and anti-HCC effect.

Materials and methods: We used RT-qPCR, Western blot, Enzyme-linked immune sorbent assay (ELISA), Flow CytoMetry (FCM) methods to examine BEA and CA's regulation of T cell mitochondrial function and anti-HCC ability. Furthermore, the mechanism of PGC-1α/DRP1 pathway on the morphology and function of T cell mitochondria was investigated.

Results: Our data demonstrated that the administration of BEA and CA, either alone or in combination, effectively suppressed HCC growth and mitigated T cell apoptosis and mitochondrial dysfunction, assessed by mitochondrial reactive oxygen species (mitoROS), mitochondrial membrane potential (MMP) and ATP level. Moreover, BEA and CA could enhance the release of tumor-killing factors (Perforin (PF) and Granzyme B (Gzm B)) from T cells, inducing H22 cell apoptosis. Additionally, BEA and CA-treated T cell reinfusion into BALB/c nude HCC mice could significantly inhibited HCC growth by promoting T cell infiltration into tumor tissue. T cell mitochondrial biogenesis/fission balance and apoptosis in tumor mice were regulated by PGC-1α/DRP1 pathway.

Conclusions: Our findings reveal that BEA and CA enhance anti-HCC effects of T cells by regulating mitochondrial biogenesis and fission through the PGC-1α/DRP1 pathway.