Anticancer Effect of Puerarin on Ovarian Cancer Progression Contributes to the Tumor Suppressor Gene Expression and Gut Microbiota Modulation

Ovarian cancer (OC) causes more deaths than any other cancer of the female reproductive system due to its late presentation and malignant nature. Although significant progress has been made in the diagnosis and treatment of OC over the last decade, chemotherapeutic drug resistance and cancer recurrence remain serious challenges in OC management. In the field of cancer therapy, traditional Chinese herbal medicines and their active compounds have been widely reported to have favorable therapeutic effects on cancer. Recent studies have also revealed the protective effect of puerarin in cancer, but the exact role and underlying mechanism of puerarin in OC remain unclear. Here, we established in vivo and in vitro OC models to evaluate the anticancer effect of puerarin. It was found that puerarin significantly inhibited OC cell viability and proliferation and induced cell apoptosis. In OC model mice, puerarin treatment suppressed tumor formation and modulated the gut microbiome. In addition, the expression of tumor suppressor genes was activated by puerarin in vitro and in vivo. These findings add to the existing knowledge on the usefulness of herbal active ingredients for the prevention and treatment of OC and provide a new perspective regarding the therapeutic potential of puerarin in cancer.

[1]  M. Fillon.  Opportunistic salpingectomy may reduce ovarian cancer risk , 2022, CA: a cancer journal for clinicians.

[2]  G. Scambia,et al.  Gut microbiota and its influence on ovarian cancer carcinogenesis, anticancer therapy and surgical treatment: a literature review. , 2021, Critical reviews in oncology/hematology.

[3]  Mingyuan Yin,et al.  Puerarin induces platinum-resistant epithelial ovarian cancer cell apoptosis by targeting SIRT1 , 2021, The Journal of international medical research.

[4]  P. Scollo,et al.  A multidisciplinary approach remains the best strategy to improve and strengthen the management of ovarian cancer (Review) , 2021, International journal of oncology.

[5]  Min Fang,et al.  Clinical Application of Chinese Herbal Injection for Cancer Care: Evidence-Mapping of the Systematic Reviews, Meta-analyses, and Randomized Controlled Trials , 2021, Frontiers in Pharmacology.

[6]  J. Szabó,et al.  The role of the microbiome in ovarian cancer: mechanistic insights into oncobiosis and to bacterial metabolite signaling , 2021, Molecular medicine.

[7]  Bo Chen,et al.  Nomograms to Predict the Density of Tumor-Infiltrating Lymphocytes in Patients With High-Grade Serous Ovarian Cancer , 2021, Frontiers in Oncology.

[8]  A. Jemal,et al.  Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries , 2021, CA: a cancer journal for clinicians.

[9]  Shanshan Cheng,et al.  Roles of CA125 in diagnosis, prediction, and oncogenesis of ovarian cancer. , 2021, Biochimica et biophysica acta. Reviews on cancer.

[10]  Haiyang Yu,et al.  Anticancer activities of TCM and their active components against tumor metastasis. , 2021, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[11]  Pan Xu,et al.  Puerarin induces apoptosis in prostate cancer cells via inactivation of the Keap1/Nrf2/ARE signaling pathway , 2020, Bioengineered.

[12]  Z. Fasoulakis,et al.  Role of Oncogenes and Tumor-suppressor Genes in Carcinogenesis: A Review , 2020, AntiCancer Research.

[13]  M. Milella,et al.  PTEN Function at the Interface between Cancer and Tumor Microenvironment: Implications for Response to Immunotherapy , 2020, International journal of molecular sciences.

[14]  B. Wang,et al.  MDMX phosphorylation-dependent p53 downregulation contributes to an immunosuppressive tumor microenvironment , 2020, Journal of molecular cell biology.

[15]  Yurii B. Shvetsov,et al.  Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium , 2020, British Journal of Cancer.

[16]  Deli Wang,et al.  Puerarin improves graft bone defect through microRNA-155-3p-mediated p53/TNF-α/STAT1 signaling pathway , 2020, International journal of molecular medicine.

[17]  Haozhen Ren,et al.  Puerarin inhibits hepatocellular carcinoma invasion and metastasis through miR-21-mediated PTEN/AKT signaling to suppress the epithelial-mesenchymal transition , 2020, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[18]  Vikas Singh,et al.  A Critical Review on Anticancer Mechanisms of Natural Flavonoid Puerarin. , 2020, Anti-cancer agents in medicinal chemistry.

[19]  G. Nabi,et al.  Molecular Mechanisms of Anticancer Activities of Puerarin , 2020, Cancer management and research.

[20]  R. Pelikan,et al.  Novel ovarian cancer maintenance therapy targeted at mortalin and mutant p53 , 2019, International journal of cancer.

[21]  E. Kohn,et al.  New strategies in ovarian cancer treatment , 2019, Cancer.

[22]  M. Birrer,et al.  Biomarkers in ovarian cancer: To be or not to be , 2019, Cancer.

[23]  N. Winer,et al.  Efficacy of HE4, CA125, Risk of Malignancy Index and Risk of Ovarian Malignancy Index to Detect Ovarian Cancer in Women with Presumed Benign Ovarian Tumours: A Prospective, Multicentre Trial , 2019, Journal of clinical medicine.

[24]  Matthew Burnell,et al.  Comparison of Longitudinal CA125 Algorithms as a First-Line Screen for Ovarian Cancer in the General Population , 2018, Clinical Cancer Research.

[25]  P. Pandolfi,et al.  The functions and regulation of the PTEN tumour suppressor: new modes and prospects , 2018, Nature Reviews Molecular Cell Biology.

[26]  A. Jemal,et al.  Ovarian cancer statistics, 2018 , 2018, CA: a cancer journal for clinicians.

[27]  K. Wiman,et al.  Targeting mutant p53 for efficient cancer therapy , 2017, Nature Reviews Cancer.

[28]  A. Shafrir,et al.  Lifestyle and Reproductive Factors and Ovarian Cancer Risk by p53 and MAPK Expression , 2017, Cancer Epidemiology, Biomarkers & Prevention.

[29]  Liu Yang,et al.  Puerarin suppresses LPS-induced breast cancer cell migration, invasion and adhesion by blockage NF-κB and Erk pathway. , 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[30]  K. Baggerly,et al.  Elevation of TP53 Autoantibody Before CA125 in Preclinical Invasive Epithelial Ovarian Cancer , 2017, Clinical Cancer Research.

[31]  Jing Zhang,et al.  Puerarin inhibits M2 polarization and metastasis of tumor-associated macrophages from NSCLC xenograft model via inactivating MEK/ERK 1/2 pathway. , 2017, International journal of oncology.

[32]  Ming Liu,et al.  Puerarin for ischaemic stroke. , 2016, The Cochrane database of systematic reviews.

[33]  Sheng-rui Wang,et al.  Protective effects of puerarin against tetrabromobisphenol a‐induced apoptosis and cardiac developmental toxicity in zebrafish embryo‐larvae , 2015, Environmental toxicology.

[34]  Cheng Peng,et al.  Puerarin: A Review of Pharmacological Effects , 2014, Phytotherapy research : PTR.

[35]  Guoqi Zhu,et al.  Involvement of activation of PI3K/Akt pathway in the protective effects of puerarin against MPP+-induced human neuroblastoma SH-SY5Y cell death , 2012, Neurochemistry International.

[36]  M. Werner,et al.  Intraepithelial CD8-positive T lymphocytes predict survival for patients with serous stage III ovarian carcinomas: relevance of clonal selection of T lymphocytes , 2009, British Journal of Cancer.

[37]  Zengli Yu,et al.  Induction of apoptosis by puerarin in colon cancer HT-29 cells. , 2006, Cancer letters.

[38]  Rochelle L. Garcia,et al.  Tumor-specific p53 sequences in blood and peritoneal fluid of women with epithelial ovarian cancer. , 2005, American journal of obstetrics and gynecology.

[39]  C. Marth,et al.  Why did p53 gene therapy fail in ovarian cancer? , 2003, The Lancet. Oncology.

[40]  S. Orsulic,et al.  Ovarian Cancer , 1993, British Journal of Cancer.