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

Abstract

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.