Potential of Kalanchoe pinnata as a Cancer Treatment Adjuvant and an Epigenetic Regulator.

Cancer is a global public health problem that is related to different environmental and lifestyle factors. Although the combination of screening, prevention, and treatment of cancer has resulted in increased patient survival, conventional treatments sometimes have therapeutic limitations such as resistance to drugs or severe side effects. Oriental culture includes herbal medicine as a complementary therapy in combination with chemotherapy or radiotherapy. This study aimed to identify the bioactive ingredients in Kalanchoe pinnata, a succulent herb with ethnomedical applications for several diseases, including cancer, and reveal its anticancer mechanisms through a molecular approach. The herb contains gallic acid, caffeic acid, coumaric acid, quercetin, quercitrin, isorhamnetin, kaempferol, bersaldegenin, bryophyllin a, bryophyllin c, bryophynol, bryophyllol and bryophollone, stigmasterol, campesterol, and other elements. Its phytochemicals participate in the regulation of proliferation, apoptosis, cell migration, angiogenesis, metastasis, oxidative stress, and autophagy. They have the potential to act as epigenetic drugs by reverting the acquired epigenetic changes associated with tumor resistance to therapy-such as the promoter methylation of suppressor genes, inhibition of DNMT1 and DNMT3b activity, and HDAC regulation-through methylation, thereby regulating the expression of genes involved in the PI3K/Akt/mTOR, Nrf2/Keap1, MEK/ERK, and Wnt/ß-catenin pathways. All of the data support the use of K. pinnata as an adjuvant in cancer treatment.

An insight into the promoter methylation of PHF20L1 and the gene association with metastasis in breast cancer.

BACKGROUND: Plant homeodomain finger protein 20-like 1 (PHF20L1) is a protein reader involved in epigenetic regulation that binds monomethyl-lysine. An oncogenic function has been attributed to PHF20L1 but its role in breast cancer (BC) is not clear. OBJECTIVES: To explore PHF20L1 promoter methylation and comprehensive bioinformatics analysis to improve understanding of the role of PHF20L1 in BC. MATERIAL AND METHODS: Seventy-four BC samples and 16 control samples were converted using sodium bisulfite treatment and analyzed with methylation-specific polymerase chain reaction (PCR). Bioinformatic analysis was performed in the BC dataset using The Cancer Genome Atlas (TCGA) trough data visualized and interpreted in the MEXPRESS website. Methylation, gene expression and survival evaluation were performed with R v. 4.0.2 software. Using multiple bioinformatic tools, we conducted a search for genes co-expressed with PHF20L1, analyzed its ontology and predicted associated miRNAs and miRNA-PHF20L1 networks. The expression and prognostic value of PHF20L1 and co-expressed genes were analyzed. RESULTS: We found demethylation in PHF20L1 promoter in both BC samples and healthy tissues. Data mining with 241 patients demonstrated changes in methylation of promoter regions in basal-like and luminal A subtypes. Expression of the PHF20L1 gene had a negative correlation with methylation. Twelve genes were co-expressed. PHF20L1 is a target of miR96-5p, miR9-5p and miR182-5p, which are involved in proliferation and metastasis. PHF20L1 gene expression was not associated with overall survival (OS), or relapse-free survival (RFS), but was associated with distant metastasis-free survival (DMFS). CONCLUSIONS: Our findings showed differences in methylation of PHF20L1 promoter region near TSS and upstream in BC subtypes; its overexpression impacted DMFS. We found that PHF20L1 is targeted by miR96-5p, miR9-5p and miR182-5p, which are involved in proliferation and metastasis, and regulates genes engaged in processes such as alternative splicing.