Houttuynia cordata Thunb (H cordata), a medicinal plant, has anticancer activity, as it inhibits cell growth and induces cell apoptosis in cancer. However, the potential anti-cancer activity and mechanism of H cordata for human liver cancer cells is not well understood. Recently, we identified hypoxia-inducible factor (HIF)-1A, Forkhead box (FOX)O3, and MEF2A as proapoptotic factors induced by H cordata, suggesting that HIF-1A, FOXO3, and MEF2A contribute to the apoptosis of HepG2 hepatocellular carcinoma cells. FOXO3 transcription factors regulate target genes involved in apoptosis. H cordata significantly increased the mRNA and protein expression of HIF-1A and FOXO3 and stimulated MEF2A expression in addition to increased apoptosis in HepG2 cells within 24 hours. Therefore, we determined the potential role of FOXO3 on apoptosis and on H cordata–induced MEF2A in HepG2 cells. HIF-1A silencing by siRNA attenuated MEF2A and H cordata–mediated FOXO3 upregulation in HepG2 cells. Furthermore, H cordata–mediated MEF2A expression enhanced caspase-3 and caspase-7, which were abolished on silencing FOXO3 with siRNA. In addition, H cordata inhibited growth of human hepatocellular carcinoma xenografts in nude mice. Taken together, our results demonstrate that H cordata enhances HIF-1A/FOXO3 signaling, leading to MEF2A upregulation in HepG2 cells, and in parallel, it disturbs the expression of Bcl-2 family proteins (Bax, Bcl-2, and Bcl-xL), which results in apoptosis. Taken together, these findings demonstrate that H cordata promotes the activation of HIF-1A–FOXO3 and MEF2A pathways to induce apoptosis in human HepG2 hepatocellular carcinoma cells and is, therefore, a promising candidate for antitumor drug development.

Ovarian cancer is one of the major causes of death among females in worldwide. Cisplatin is a primary anti-cancer drug against ovarian cancer, but the recurrent tumors after treatment frequently show acquired chemoresistance. Extract of Scutellaria baicalensis (SbE) has been reported to have functional compounds including baicalin, which has anti-cancer effects. However, the anti-cancer effects of SbE in ovarian cancer and its underlying mechanisms are elusive. We investigated that the effects of SbE and/or cisplatin on cell death in the cisplatin sensitive ovarian cancer cell line A2780 (CSC) and the counterpart cell line that has cisplatin resistance (CRC). Molecular mechanisms of the effects, focusing on apoptosis and autophagy, were examined. Treatment of cisplatin or SbE reduced cell viability significantly in CSC and too much lesser extent in CRC. Cisplatin-induced cell death in CSC was mediated by p53-induced apoptosis acompanied by expresson of damage-regulated autophagy modulator (DRAM). In CRC, decreased DRAM expression (p < 0.01) hindered p21-mediated cell death and contributed to cisplatin resistance. Treatment of SbE also induced cell death in CSC by p53-dependent apoptosis, not in CRC. Autophagy was not induced by neither cisplatin nor SbE. Intriguingly, the combinational treatment of SbE and cisplatin significantly decreased cell viability in CRC. The cell death was mediated by autophagy with increased expression of Atg5 and Atg12 (p < 0.05), rather than p53-dependent pathway with repressed expression of p21 (p < 0.001) through HDAC1 activation. The combined treatment of SbE with cisplatin was effective in CRC, leading to cell death via Beclin1-independent autophagy, suggesting that SbE treatment in combination with cisplatin has a potential as a chemotherapeutic agent in cisplatin-resistant ovarian cancer.

Background: Modulation of the gut–brain axis using probiotics present a promising approach for enhancing cognitive function in mild cognitive impairment (MCI). In prior non-clinical research, Lactobacillus delbrueckii subsp. lactis CKDB001 (LL) exhibited potential to enhance cognitive function. We therefore conducted a clinical trial to assess the efficacy and safety of LL supplementation in MCI. Methods: A 12-week, randomized, double-blind, placebo-controlled, multi-center trial was performed in 100 participants aged 55–80 years. Subjects were randomly assigned to receive LL (n = 50, 5.0 × 10⁹ CFU/day) or placebo (n = 50). Efficacy and safety were evaluated at baseline and after 12 weeks. Results: LL supplementation resulted in significantly greater improvements than placebo in the Alzheimer’s Disease Assessment Scale–Cognition 13 total score, the memory sub-score, reaction time for Part A of the Trail Making Test, and word/color reaction times on the Stroop test. Taxonomic and metabolomic profiling of fecal samples showed significantly greater changes in the relative abundance of beneficial microorganisms in the LL group, with the most pronounced shifts at the family (Lactobacillaceae, Bifidobacteriaceae) and genus (Lactobacillus) levels. In addition, the LL group exhibited significantly higher fecal levels of indole-derived metabolites, including 5-hydroxyindole-3-acetic acid, indole-3-lactic acid, and indole-3-glycol. Safety assessments indicated LL was safe and well-tolerated, with no clinically relevant changes in laboratory findings or adverse events. Conclusions: These findings suggest that LL supplementation may enhance cognitive function in MCI by modulating the gut–brain axis through effects on gut microbiota and related metabolites, and could serve as a safe functional food to support cognitive health.

Lei Shen, Jong Ha Lee, Jong Cheon Joo, Soo Jung Park, and Yung Sun Song. J Pharmacopuncture 2020;23:44-53. https://doi.org/10.3831/KPI.2020.23.008

Ovarian cancer is the gynecological malignancy with the poorest prognosis, in part due to its high incidence of recurrence. Platinum agents are widely used as a first-line treatment against ovarian cancer. Recurrent tumors, however, frequently demonstrate acquired chemo-resistance to platinum agent toxicity. To improve chemo-sensitivity, combination chemotherapy regimens have been investigated. This study examined anti-tumor effects and molecular mechanisms of cytotoxicity of Oldenlandia diffusa (OD) extracts on ovarian cancer cells, in particular, cells resistant to cisplatin. Six ovarian cancer cells including A2780 and cisplatin-resistant A2780 (A2780cis) as representative cell models were used. OD was extracted with water (WOD) or 50% methanol (MOD). MOD significantly induced cell death in both cisplatin-sensitive cells and cisplatin-resistant cells. The combination treatment of MOD with cisplatin reduced viability in A2780cis cells more effectively than treatment with cisplatin alone. MOD in A2780cis cells resulted in downregulation of the epigenetic modulator KDM1B and the DNA repair gene DCLRE1B. Transcriptional suppression of KDM1B and DCLRE1B induced cisplatin sensitivity. Knockdown of KDM1B led to downregulation of DCLRE1B expression, suggesting that DCLRE1B was a KDM1B downstream target. Taken together, OD extract effectively promoted cell death in cisplatin-resistant ovarian cancer cells under cisplatin treatment through modulating KDM1B and DCLRE1B.

Background: Cervical cancer is the fourth most common malignant tumor among women worldwide. This study aimed to evaluate the efficacy of Astragalus-containing Chinese herbal medicine (CHM) combined with chemotherapy (CT) for the treatment of cervical cancer.Methods: Ten electronic databases including PubMed, Cochrane Library, Embase, Korean databases, and Chinese medical databases, were systematically searched up to July 2020. All randomized controlled trials using Astragalus-containing CHM combined with CT to treat cervical cancer were included.Results: A total of 19 trials were included in the analysis. Compared with the control group, the Astragalus-containing CHM combined with CT group showed a significantly increased tumor response (complete and partial response (CR and PR)) (risk ratio [RR] = 1.25, 95% confidence interval [CI]: 1.17–1.33, p &lt; 0.00001) and Karnofsky performance score (KPS) (standardized mean difference [SMD] = 1.81, 95% CI: 1.46–2.17, p &lt; 0.00001). This group also displayed remarkably reduced CT toxicity.Conclusion: Our study suggests that Astragalus-containing CHM might be a potential option for cervical cancer to enhance the curative efficacy and reduce CT toxicity.