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bioRxiv2025

A combination of the extract from Phellinus linteus with Smilax spp. attenuates colorectal and prostate cancers

The current study investigated the effects of Thai remedy herbal extracts from Phellinus linteus (PL) and a combination of P. linteus with Smilax corbularia and S. glabra (PSS) on colorectal, prostate cancer cell lines, along with kidney cell lines in vitro, as well as their effects on mice subcutaneously injected with colorectal cancer cells. The IC50 values of PSS and PL were evaluated using the MTT assay, and their effects on cell cycle distribution and apoptosis induction were examined. RT-qPCR was performed to analyze the expression of proliferation-related genes following treatment with PSS and PL. Tumor-associated macrophages (TAMs) were also treated with these extracts to assess gene expression related to macrophage polarization, and macrophages tumoricidal activity was measured using CFDA-SE-labeled cancer cells. In addition, an animal tumor xenograft model was employed to determine the in vivo efficacy of PSS and PL. The results revealed that both PSS and PL exerted cytotoxic effects on colorectal, prostate, and kidney cancer cell lines. PSS induced G2 phase arrest in all colorectal cancer cell lines but not in PC3 cells and showed a mild effect on apoptosis induction in colorectal and prostate cancer cells. The inhibition of proliferation was partly associated with the downregulation of genes involved in cancer progression by both PL and PSS. Moreover, PL and PSS interfered with cancer supernatant-stimulated macrophages, upregulating M1-associated genes and downregulating M2-associated genes. In vivo, PSS reduced tumor volume in HCT116 cell-injected mice, and co-incubation of fluorescently labeled HCT116 cells with TAMs and PSS decreased fluorescence intensity, whereas PL alone did not exhibit these effects. Collectively, these findings indicate that both PL and PSS inhibit cancer cell proliferation in vitro, but only PSS demonstrated significant antitumor activity in vivo.

cancer biology↗

bioRxiv2024

Cgas deficiency promotes tumor growth by supporting B cell persistence and angiogenesis

The cGAS sensor activates STING/IFN signaling, which is crucial for immune defense against pathogens and triggers inflammation in autoimmune diseases and antitumor responses. This study investigated the cGAS-mediated immune response in tumorigenesis using the MC-38 tumor model. Cgas-/- mice exhibited significantly larger tumors and lower survival rates than wild-type (WT) mice. Tumors in Cgas-/- mice showed increased fibrosis and neovascularity. WT mice mounted a more robust T-cell-mediated antitumor response, with higher levels of NK and effector T cells, while Cgas-/- mice showed an expansion of B cells, including regulatory B cells producing IL-10. B cells from tumor-bearing Cgas-/- mice survived better in the tumor- conditioned medium than those from WT mice. B cell depletion significantly reduced tumor size in WT mice but had minimal effect in Cgas-/- mice, where fibrosis and tumor vasculature persisted. Despite B cell depletion, B cells remained in the tumors of Cgas-/- mice, in contrast to WT mice, where their reduction correlated with an increase in CD8+ infiltrating cells. Expression of Tlr7 and Tlr9 remained elevated and unaffected by B cell depletion in Cgas-/- tumors, while Baff expression was higher and further increased after B cell depletion. Cgas-/- B cells promoted angiogenesis, as indicated by enhanced endothelial tube formation. In summary, cGAS deficiency fosters a tumor microenvironment that supports B cell survival, promotes a pro-tumor immune environment, and enhances angiogenesis, contributing to tumor progression.

cancer biology↗