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

Abstract

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.

The Gut Microbiome in Aging and Ovarian Cancer

“…This group further confirmed that the main benefit to Akkermansia was increased fecal acetate levels, which promoted CD8 + T‐cell cancer‐killing ability via IFN‐γ [16]. Another study on rats injected with syngeneic ovarian cancer cells found decreased Akkermansia in the tumor‐bearing rats compared to the tumor‐naïve rats [34].…”

“…An Italian study comparing ovarian cancer patients ( n = 24) at the time of diagnosis to demographically matched healthy controls ( n = 24) noted similar alpha diversity between the two groups [18]. These findings were corroborated in a rat model of ovarian cancer metastasis, where the gut alpha diversity of rats injected intraperitoneally with syngeneic ovarian cancer cells did not differ significantly from that of saline‐injected rats [34]. Lack of significant difference in the gut microbiome is also seen when comparing ovarian cancer patients to groups other than healthy subjects.…”

“…The current evidence for causal relationships between gut microbiome changes and ovarian cancer symptoms is limited to the two studies in which treatment of ovarian cancer-bearing mice with FMT from ovarian cancer patients promoted tumor growth via IFN-γ and CD8 + T cell or Hedgehog and TNF-α/IL-1β pathways [16,17]. Research on the benefits of gut microbiome remediation in ovarian cancer treatment is limited to a few studies in which mice have benefitted from FMT from healthy donors or their own stool banked prior to chemotherapy [16,17,25], or pilot studies showing gut microbiome modulation via Traditional Chinese Medicine [23,34,103]. Importantly, to our knowledge, there are no clinical trials on gut microbiome remediation to enhance ovarian cancer treatment.…”

“…Traditional Chinese medicines have been shown to modulate the gut microbiome and reduce tumor burden in rodent models of ovarian cancer. However, the changes seen in the gut microbiome in each study do not overlap well between studies, do not line up well with changes seen in human ovarian cancer patients compared to control subjects, and do not result in the experimentally treated animals having a gut microbiome that better resembles their respective tumor‐naïve controls [23, 34, 103]. The lack of similarity in gut microbiome changes between experiments is reasonable considering that each study was testing a different compound.…”

Pueraria protein extract inhibits melanogenesis and promotes melanoma cell apoptosis through the regulation of MITF and mitochondrial‑related pathways

“…Using an extracellular screening model, it was found that a P. Lobata Radix water-soluble total protein extract (PLP) strongly inhibited tyrosinase activity. As this PLP inhibited tyrosinase and P. Lobata Radix has been reported to have anti-cancer activity ( 19 , 20 ), there is interest in investigating the effect of PLP on melanin formation in melanoma.…”