The plant extract ofPao pereirapotentiates carboplatin effects against ovarian cancer

Abstract

Context: Herbal preparation of Pao pereira [Geissospermum vellosii Allem (Apocynaceae)] has long been used by oncologic patients and Integrative Medicine practitioners in South America. However, its anticancer activities have not been systematically studied. Objective: To investigate the anticancer effects of b-carboline alkaloids-enriched extract from Pao pereira (Pao), either alone or in combination with carboplatin, in preclinical ovarian cancer models. Materials and methods: Cytotoxicity of Pao (0-800 mg/ml) against different ovarian cancer cell lines and an immortalized epithelial cell line was detected by flow cytometry, MTT assay and colony formation in soft agar. Combination of Pao and carboplatin, a primary chemotherapeutic drug for ovarian cancer, was evaluated using Chou-Talalay's methods. Mice bearing intraperitoneally spread ovarian cancer were treated with 20 or 50 mg/kg/day Pao by i.p. injection. Carboplatin at 15 mg/kg/week i.p. was compared and combined to Pao treatments. Results: Pao selectively inhibited ovarian cancer cell growth with IC 50 values of 180-235 mg/ml, compared to 537 mg/ml in normal cells. Pao induced apoptosis dose-and time-dependently and completely inhibited colony formation of tumor cells in soft agar at 400 mg/ml. Pao greatly enhanced carboplatin cytotoxicity, with dose reduction (DRIs) for carboplatin at 1.2-10 fold. In vivo, Pao alone suppressed tumor growth by 79% and decreased volume of ascites by 55%. When Pao was combined with carboplatin, tumor inhibition reached 97% and ascites was completely eradicated. Discussion and conclusion: Pao possess potent antitumor activity and could enhance carboplatin effect, and therefore holds therapeutic potential in the treatment of ovarian cancer.

Pao Pereira Extract Attenuates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by inhibiting 5α-Reductase

“…Pao extract is a β-carboline alkaloids-enriched extract and the active components of the same genus of Pao were β-carboline alkaloids and indole alkaloids 27 . Flavopereirine (Fla) alkaloid isolated from Pao is a pharmaceutical important alkaloid, which possesses several biological activities, such as DNA damaging, antiplasmodial activity and cytotoxicity 35–37 .…”

“…Consistent with the suppressive effects of Pao extract on highly proliferative cells in BPH model, we and other group have demonstrated that Pao extract induced cell growth arrest and apoptosis in LNCaP and PC3 prostate cancer cells, as well as ovarian and pancreatic cancer cells 25,26 . In addition, Pao extract has been shown to inhibit multiple signaling pathways other than hormone-related signaling, such as Wnt/β-catenin and NFκB signaling in various cancer cells 27,29 . Notably, there is a causal link between prostatic inflammation and BPH development by epidemiological study 43,44 .…”

“…Recent studies revealed that a β-carboline alkaloid-enriched Pao extract has inhibitory effects on two prostate cancer lines, LNCaP and PC3 by inhibiting cell proliferation and survival 25,26 . Moreover, Pao extract can also chemosensitize ovarian cancer cells to carboplatin and pancreatic cancer cells to gemcitabine, respectively 27–29 . Given that BPH is caused by increased proliferative rates of prostate epithelial and stromal cells, we hypothesize that Pao extract can suppress BPH development by inhibiting prostate cell proliferation.…”

Extract of the Medicinal Plant Pao Pereira Inhibits Pancreatic Cancer Stem-Like Cell In Vitro and In Vivo

“…The extract of the bark of Pao Pereira (Pao) has long been used in complementary and alternative medicine on cancer patients, and has been reported recently to have tumor inhibitory effect toward prostate, ovarian and pancreatic cancers. 20 , 24 - 26 We previously reported that Pao induced pancreatic cancer cells apoptosis, and inhibited pancreatic tumor growth in mice. 25 The combination of Pao and gemcitabine showed synergistic antitumor effects.…”

Pao Pereira extract suppresses benign prostatic hyperplasia by inhibiting inflammation-associated NFκB signaling

“…Pao pereira (Geissospermum vellosii) is an Amazon rainforest tree, and its bark extract is used to treat malaria, digestive disorders and cancers. Pao extract is rich in β-carboline alkaloids [8] and exhibited antiproliferative activities against melanoma and glioblastoma, ovarian cancer and pancreatic cancer [9][10][11][12][13]. Our previous study showed that Pao extract decreased human prostate cancer cell growth via inducing apoptosis [14].…”