Boswellia (Boswellia serrata) and Cancer (anticancer research): evidence and sources

Ethnopharmacological relevance Increasing research on traditional herbal medicines and their phytoconstituents has recognized their usefulness in complementary as adjuvant to chemotherapy in various types of cancers. The oleo-gum resin of Boswellia serrata tree is one such folk medicine, which has been traditionally used for religious, cosmetic as well as medical purposes since ages. The oleo-gum resin of the plant has been used in traditional medicine to treat variety of conditions including inflammatory diseases like arthritis, asthma, chronic pain, bowel conditions and many other diseases. This review presents an overview of scientific studies on cytotoxic and antitumor properties of B. serrata and its constituents. Materials and methods Literature search was carried out for activities of B. serrata and various isolated boswellic acids such as β-boswellic acid, 11-keto-β-boswellic acid and acetyl-11-keto-β-boswellic acid reported in various cancer types in vitro as well as in vivo. Results The triterpenoidal fraction of B. serrata (containing boswellic acids) is responsible for the cytotoxic and antitumor properties. Among the screened compounds, 3-O-acetyl-11-keto-β-boswellic acid has been found to be most promising cytotoxic molecule. The cytotoxic and antitumor effects are mainly due to induction of apoptosis through caspase activation, increased Bax expression, NF-κB down regulation and induction of poly (ADP)-ribose polymerase (PARP) cleavage. Conclusions Boswellic acids appear to be promising candidates for anticancer drug development in future. However, further in vivo studies are needed. Studies in combination with clinically used anticancer drugs and QSAR studies on individual boswellic acid also need to be carried out.

Objectives Colorectal cancer (CRC) is one of the most common cancers all over the world. The progression of CRC is associated with inflammation and disruptions in intestinal flora. 3-O-Acetyl-11-keto-β-boswellic acid (AKBA) has been noted for its potent anti-inflammatory properties. However, the effect of AKBA on colon cancer caused by inflammation and its mechanism are not unclear. The study is to explore the effect of AKBA on CRC and its mechanism. Materials and methods Cell proliferation, (5-ethynyl-2 ' -deoxyuridine, EdU)-DNA synthesis assay and colony formation were used to assess the effect of AKBA on the proliferation of CRC cells. Flow cytometry was employed to analyze the cell cycle and apoptosis rate of cells treated with AKBA. RNA sequencing was done to explore the underlying mechanisms of AKBA. Western blot was used to assess the expression of key proteins in the nuclear factor kappa-B (NF-κB) signaling pathway after the treatment of AKBA. Real-time quantitative PCR (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and Meso Scale Discovery (MSD) assays were employed to check the anti-inflammation effects of AKBA on Lipopolysaccharide (LPS)-induced RAW264.7 cells and LPS-induced mouse model. Additionally, the Azoxymethane/Dextran sulfate sodium (AOM/DSS)-induced colitis-associated CRC model was used to evaluate the anti-CRC effect of AKBA. Gut microbiota profiling of fecal samples from CRC mice, both with and without AKBA treatment, was conducted through metagenomic sequencing analysis. Results Our results showed that AKBA reduced the proliferation of HCT116 and SW620 cells, increased apoptosis of cells, and arrested the cell cycle at the G2/M phase. Results from RNA-seq showed that AKBA inhibited CRC by inhibiting the NF-κB signaling pathway and reducing cellular inflammation. Furthermore, AKBA reduced the levels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), Interferon-γ (IFN-γ), Interleukin-IL-12p70 (IL-12p70), Interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in both the spleen and serum of LPS-induced acute inflammation mice. Additionally, AKBA inhibited the development of AOM/DSS-induced colitis-associated colon cancer in mice and positively influenced gut microbiota. Conclusion This study highlights the inhibitory effect of AKBA on colitis-associated CRC and reveals a novel aspect of its role in the remodeling of gut microbiota. These findings suggest that AKBA may be used as a potential therapeutic agent for CRC.

Background 3-acetyl-11-keto-beta-boswellic acid (AKBA) is a monomer extracted from the traditional Chinese herbs of Boswellia that has antitumor effects. However, the therapeutic effects and mechanisms of AKBA in prostate cancer (PCa) are unclear. Objective To predict the target of AKBA treatment of PCa using network pharmacology methods and validate the predicted targets through CCK-8, flow cytometry, cell scratch test, Transwell chamber assay, and proteomics. Methods The protein-protein interaction (PPI) network was established. Further analysis was performed by gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes for biological functionality and pathway enrichment. CCK-8 assay, flow cytometry, wound healing assay, and Transwell chamber assay were used to detect cell proliferation, apoptosis, invasion, and metastasis, respectively. Transcriptomics was used to detect the effects of AKBA on protein levels in PCa cells. Results 120 potential targets for the AKBA treatment of PCa were obtained. GO enrichment analysis revealed that the biological processes of AKBA treatment of PCa include the steroid metabolic process, drug response, and fatty acid metabolic process. The results of KEGG enrichment revealed that the IL-17 signaling pathway is the key pathway for the AKBA treatment of PCa. In addition, experimental results demonstrate that AKBA inhibits the proliferation of PCa cells, induces cell apoptosis, and suppresses cell invasion and metastasis. Proteomics identified 119 differentially expressed proteins, which were primarily enriched in pathways closely related to the phogosome, pathways in cancer, IL-17 signaling pathway, spliceosome, PPAR signaling pathway, and HIF-1 signaling pathway. Conclusion Through the methodologies of network pharmacology and transcriptomics, AKBA may exert its therapeutic effects on PCa by modulating the expression of the IL-17 signaling pathway.

There has been a lot of interest in using naturally occurring substances to treat a wide variety of chronic disorders in recent years. From the gum resin of Boswellia serrata and Boswellia carteri, the pentacyclic triterpene molecules known as boswellic acid (BA) are extracted. We aimed to provide a detailed overview of the origins, chemistry, synthetic derivatives, pharmacokinetic, and biological activity of numerous Boswellia species and their derivatives. The literature searched for reports of B. serrata and isolated BAs having anti-cancer, anti-microbial, anti-inflammatory, anti-arthritic, hypolipidemic, immunomodulatory, anti-diabetic, hepatoprotective, anti-asthmatic, and clastogenic activities. Our results revealed that the cytotoxic and anticancer effects of B. serrata refer to its triterpenoid component, including BAs. Three-O-acetyl-11-keto-BA was the most promising cytotoxic molecule among tested substances. Activation of caspases, upregulation of Bax expression, downregulation of nuclear factor-kappa B (NF-kB), and stimulation of poly (ADP)-ribose polymerase (PARP) cleavage are the primary mechanisms responsible for cytotoxic and antitumor effects. Evidence suggests that BAs have shown promise in combating a wide range of debilitating disease conditions, including cancer, hepatic, inflammatory, and neurological disorders.

Objective Acetyl-11-keto-β-boswellic acid (AKBA) is a triterpenoid, which is the main component of boswellic acid from Boswellia Serrata, a medicinal plant that has shown immense potential in anti-cancer therapy. This study aims to explore the roles and molecular mechanisms of AKBA on cell behavior in non-small cell lung cancer (NSCLC) cells. Materials and methods The effects of AKBA on the cell viability in A549, H460, H1299, and BEAS-2B cells were determined by the CCK-8 assay. The colony formation assay was used to identify the effects of AKBA on cell proliferation. Potential roles of AKBA in regulating the cell cycle, apoptosis, and autophagy in A549 were evaluated by flow cytometry, Western blotting, reverse transcription-polymerase chain reaction (PCR) and immunofluorescence (IF). Results AKBA reduced cell viability in A549, H460, H1299, and BEAS-2B. In A549 cells, AKBA suppressed the clone formation, arrested the cell cycle at the G 0 /G 1 phase, induced cellular apoptosis. We found that AKBA suppressed the formation of autolysosome, and decreased the expression levels of Beclin-1, LC3A/B-I, and LC3A/B-II proteins. Furthermore, AKBA also inhibited the expression levels of PI3K/Akt signaling pathway proteins. Conclusion AKBA exerts the anti-cancer effects via cell cycle arrest, apoptosis induction, and autophagy suppression in NSCLC cells. This body of evidence supports the potential of AKBA as a promising drug in the treatment of NSCLC.