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Introduction
Our interest is in basic and translational research in natural products as inhibitors of cancer cell epithelial-mesenchymal transition (EMT), and cancer stem cells (CSCs). Our current focus includes vitamin C, novel derivatives of histone deacetylase inhibitors (HDACi). We also have high-throughput screening project looking for novel EMT inhibitors for discovery of inhibitors for pancreatic cancer stem cells.
Additional affiliations
February 2004 - October 2008
May 2002 - July 2002
Chinese Academy of Sciences, Shanghai Institute of Materian Medica
Position
- Visiting Student
June 1998 - January 2004
Publications
Publications (79)
Background
Intravenous vitamin C (IVC, ascorbate [Asc]) and alpha-lipoic acid (ALA) are frequently coadministered in integrative oncology clinics, with limited understanding of combination effects or drug-drug interactions. As high-dose IVC has anticancer activity through peroxide (H2O2), it is hypothesized that IV ALA, a thiol antioxidant, might h...
Neoadjuvant cisplatin based chemotherapy is considered standard of care for patients with locally advanced bladder cancer (BCa). However, upwards of 50% of patients are ineligible due to poor performance status, underlying kidney disease, peripheral neuropathy, hearing loss and/or cardiac disease. There are currently no accepted alternative regimen...
Pancreatic cancer is a devastating disease with a dismal prognosis and poor treatment outcomes. Searching for new agents for pancreatic cancer treatment is of great significance. We previously identified a novel activity of compound C150 to inhibit pancreatic cancer epithelial-to-mesenchymal transition (EMT). Here, we further revealed its mechanism...
Purpose:
Intravenous vitamin C (IVC) is used in a variety of disorders with limited supporting pharmacokinetic data. Herein we report a pharmacokinetic study in healthy volunteers and cancer participants with IVC doses in the range of 1-100 g.
Methods:
A pharmacokinetic study was conducted in 21 healthy volunteers and 12 oncology participants. H...
e16540
Background: Neo-adjuvant cisplatin-based chemotherapy (NAC) is considered standard of care for patients with locally advanced disease. However, ̃40% of patients are cisplatin ineligible (CI) due to renal insufficiency, hearing loss or poor performance status. Gemcitabine and carboplatin (GCa) has limited success in this setting. Patients usu...
Pancreatic cancer cell epithelial-to-mesenchymal transition (EMT) is an important contributor to cell invasion and tumor progression. Therefore, targeting EMT may be beneficial for pancreatic cancer treatment. The aim of the present study was to report on the inhibitory effect of the novel compound C150 on the EMT of pancreatic cancer cells. C150 i...
Pancreatic cancer has poor prognosis and treatment outcomes due to its highly metastatic nature and resistance to current treatments. The RNA binding protein (RBP) Hu-antigen R (HuR) is a central player in posttranscriptional regulation of cancer related gene expression, and contributes to tumorigenesis, tumor growth, metastasis and drug resistance...
Objective
Epithelial to Mesenchymal Transition (EMT) has been proposed to contribute importantly to metastasis, cancer stem cell (CSC) generation and drug resistance in many cancers. Targeting EMT may be promising to benefit cancer treatment. Our previous high throughput screening study has identified a potential EMT inhibitor (namely, C150) in pan...
Interests have risen in the research into using pharmacologic doses of ascorbate for cancer treatment, due to its potential efficacy and low toxicities. It has been revealed that the anticancer activity of ascorbate is primarily attributed to its pro-oxidant effect for hydrogen peroxide (H2O2) generation in the extracellular spaces, which reduces t...
The promise of poly(ADP-ribose) polymerase inhibitors (PARPis) in the management of epithelial ovarian cancer (EOC) is hampered by the limited clinical activity against BRCA wild-type or homologous recombination-proficient EOC. In order to decrease the resistance and increase the efficacy of PARPis, combination treatments of pharmacological ascorba...
Objectives
Epithelial‐mesenchymal transition (EMT) contributes importantly to cancer cell metastasis and formation of cancer stem cells (CSC). An RNA‐binding protein, HuR, regulates gene expressions involved in tumor cell proliferation, metastasis, anti‐apoptosis, and drug resistance. The role of HuR in cancer cell EMT and CSC has not been elucidat...
Objectives
Ovarian cancer has an enrichment of stem‐like cancer cells (CSCs) which contribute to the treatment‐resistant tumor's high rate of recurrence and metastasis. Here we investigated two extracts from the medicinal plants Pao Pereira (Pao) and Rauwolfia vomitoria (Rau) each for their activities against ovarian CSCs.
Methods
The Pao and Rau...
Objective
Epithelial to Mesenchymal Transition (EMT) has been proposed to contribute importantly to metastasis, cancer stem cell (CSC) generation and drug resistance in many cancers. Targeting EMT may be promising to benefit cancer treatment. Our previous high throughput screening study has identified a potential EMT inhibitor (namely, C150) in pan...
The poor treatment outcomes of pancreatic cancer are linked to an enrichment of cancer stem cells (CSCs) in these tumors, which are resistant to chemotherapy and promote metastasis and tumor recurrence. The present study investigated an extract from the root of the medicinal plant Rauwolfia vomitoria (Rau) for its activity against pancreatic CSCs....
Pancreatic cancers are enriched with cancer stem-like cells (CSCs), which are resistant to chemotherapies, and responsible for tumor metastasis and recurrence. Here, we investigated the extract of a medicinal plant Pao Pereira (Pao) for its activity against pancreatic CSCs. Pao inhibited overall proliferation of human pancreatic cancer cell lines w...
Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis and is often discovered at an advanced stage with few therapeutic options. Current conventional regimens for PDA are associated with significant morbidity, decreased quality of life, and a considerable financial burden. As a result, some patients turn to integrative medicine therapies as...
Pancreatic cancer is among the most lethal cancers with poorly tolerated treatments. There is increasing interest in using high-dose intravenous ascorbate (IVC) in treating this disease partially because of its low toxicity. IVC bypasses bioavailability barriers of oral ingestion, provides pharmacological concentrations in tissues, and exhibits sel...
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In May 2016, the Office of Cancer Complementary and Alternative Medicine, Division of Cancer Diagnosis and Treatment, of the National Cancer Institute convened a special workshop focused on the State of the Science: Cancer Complementary and Alternative Medicine Therapeutics Research. The current state of the science, gaps, and future opportunities...
An ascorbate-mediated production of oxidative stress has been shown to retard tumor growth. Subsequent glycolysis inhibition has been suggested. Here, we further define the mechanisms relevant to this observation. Ascorbate was cytotoxic to human neuroblastoma cells through the production of H2O2, which led to ATP depletion, inhibited GAPDH, and no...
Background
Pancreatic cancer has an enrichment of stem-like cancer cells (CSCs) that contribute to chemoresistant tumors prone to metastasis and recurrence. Drug screening assays based on cytotoxicity cannot identify specific CSC inhibitors, because CSCs comprise only a small portion of cancer cell population, and it is difficult to propagate stabl...
Purpose
Epithelial- mesenchymal transition (EMT) contributes importantly to cancer cell metastasis, and formation of cancer stem cells (CSCs). An RNA-binding protein, HuR, plays an important role in many solid tumors for promoting cell proliferation, metastasis, anti-apoptosis and drug resistance. However, the role of HuR in cancer cell EMT and CSC...
Purpose:
High-dose intravenous ascorbate (IVC) bypasses bioavailability barriers of oral ingestion and provides pharmacologic concentrations in tissues, and exhibits pro-oxidant anti-cancer activities. In pancreatic cancer pre-clinical models, ascorbate has been shown to sensitize the tumor to the 1st line chemotherapeutic drug gemcitabine. Here, w...
Pancreatic cancer is one of the most lethal cancers among all malignances, with a median overall survival of <1 year and a 5-year survival of ~5%. The dismal survival rate and prognosis are likely due to lack of early diagnosis, fulminant disease course, high metastasis rate, and disappointing treatment outcome. Pancreatic cancers harbor a variety...
Background:
Glycogen synthase kinase 3β (GSK3B, GSK-3β) is a multi-functional protein kinase involved in various cellular processes and its activity elevates after serum deprivation. We have shown that inhibition of GSK-3β activity triggered a profound autophagic response and subsequent necrotic cell death after serum deprivation in prostate cance...
The present study investigates the anticancer effect of ascorbate in MIA-PaCa-2 human pancreatic cancer cells using both in vitro and in vivo models, with a focus on assessing the role of oxidative stress and autophagy as important mechanistic elements in its anticancer actions. We showed that ascorbate suppresses the growth of human pancreatic can...
Effectiveness and low-toxicity to normal tissues are ideal properties for a cancer treatment, and one that numerous research programs are aiming for. Vitamin C has long been used in the field of Complementary and Alternative Medicine as a cancer treatment, with profound safety and anecdotal efficacy. Recent studies revealed the scientific basis for...
Pancreatic cancer is one of the most lethal malignancies with very limited treatment option. In the effort of enhancing the effect of the conventional chemotherapeutic drug gemcitabine against pancreatic cancer, we investigated IN VITR: and IN VIV: the anticancer effect of a β-carboline-enriched extract from the plant RAUWOLFIA VOMITORI: (Rau), eit...
The prenyl diphosphate synthase subunit 2 (PDSS2) gene has recently been proposed as a novel tumor suppressor in several types of solid tumors. However, the mechanism of its tumor-suppressing activity is not known. Our previous study found a decreased expression of PDSS2 in clinical samples of non-small-cell lung cancer, and an inverse correlation...
Ascorbate (vitamin C) was an early, unorthodox therapy for cancer, with an outstanding safety profile and anecdotal clinical benefit. Because oral ascorbate was ineffective in two cancer clinical trials, ascorbate was abandoned by conventional oncology but continued to be used in complementary and alternative medicine. Recent studies provide ration...
Background
Tumor resistance to platinum-based drugs has been an obstacle to the treatment of ovarian cancer. Extract of the plant Rauwolfia vomitoria has long been used by cancer patients. However, there have not been systematic studies of its anticancer activity.Objective
In an effort to enhance the effectiveness of platinum-based drugs, we invest...
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 β-carboline alkaloids-enriched extra...
Objective:
A simple method of using fingerstick blood glucose (FSBG) monitors to estimate blood ascorbate values after high-dose intravenous (IV) ascorbate infusion is evaluated as a substitution for high-performance liquid chromatography (HPLC) measurement.
Methods:
In 33 participants, readings from FSBG monitors were taken before and after IV...
Lack of effective therapy is a major problem in the treatment of pancreatic cancer. In the present study, we investigated a natural product, the extract of Pao Pereira (Pao), for its anti-pancreatic cancer effect in vitro and in vivo, either alone or in combination with the first-line chemotherapeutic drug gemcitabine (Gem). Pao induced dose-depend...
Background:
Prenyl diphosphate synthase subunit 2 (PDSS2) gene has recently been reported as a potential tumor suppressor. The association of PDSS2 and non-small cell lung cancer (NSCLC) has not been known.
Methods:
To investigate its association with NSCLC, we examined the expression level of PDSS2 in 28 paired clinical samples of non-small cel...
Pharmacologic concentrations of ascorbate have been shown to act as a pro-oxidant anti-cancer agent. Our previous work has showed that pharmacologic ascorbate worked synergistically with gemcitabine in 8 pancreatic cancer cells lines, and in gemcitabine responsive and non-responsive mouse tumor models. This study aimed to investigate the mechanisms...
Purpose To evaluate extracts from two medical plants Pao Per-eira (Pao) and Rauwolfia vomitoria (Rau) for their anti-tumor effects in various types of pancreatic cancers and ovarian cancers. Methods Five pancreatic cancer and three ovarian cancer cell lines were tested that exhibited different resistance to the 1st line chemo-drug gemcitabine (Gem,...
Recent studies have revealed the scientific basis for the use of intravenous (i.v.) vitamin C or ascorbic acid (ascorbate) in treating cancers, and raised the possibility of using i.v. ascorbate as a prooxidant anticancer therapy. Through the production of H2O2, pharmacologic ascorbate can induce some cancer cell death in vitro and inhibit a number...
Two popular complementary, alternative, and integrative medicine therapies, high-dose intravenous ascorbic acid (AA) and intravenous glutathione (GSH), are often coadministered to cancer patients with unclear efficacy and drug-drug interaction. In this study we provide the first survey evidence for clinical use of iv GSH with iv AA. To address ques...
Conventional treatment approaches have had little impact on the course of pancreatic cancer, which has the highest fatality rate among cancers. Gemcitabine, the primary therapeutic agent for pancreatic carcinoma, produces minimal survival benefit as a single agent. Therefore, numerous efforts have focused on gemcitabine combination treatments. Usin...
Anecdotal information and case reports suggest that intravenously administered vitamin C is used by Complementary and Alternate Medicine (CAM) practitioners. The scale of such use in the U.S. and associated side effects are unknown.
We surveyed attendees at annual CAM Conferences in 2006 and 2008, and determined sales of intravenous vitamin C by ma...
The syntheses, characterizations and in vitro cytotoxities of seven soluble silver (I) compounds (1–7) with 2,2′-bipyridine (bpy), 5,5′-dimethyl-2,2′-bipyridine (dmbpy) and 1, 10-phenanthroline (phen) are described. Two of the complexes, [Ag(dmbpy)(NO3)] (1) and [Ag(dmbpy)]ClO4(2), have been structurally established by single-crystal X-ray diffract...
Ascorbate (Vitamin C) has been shown to act as a pro‐oxidant agent under pharmacological concentrations, and thus can cause cancer cell death in vitro and inhibit tumor growth in animal models, through formation of H2O2. The cell death mechanisms induced by ascorbate need to be further elaborated.
The goal of our study was to determine whether asco...
To the Editor: On the basis of cell and animal experiments with dehydroascorbic acid, Heaney and colleagues state, "These results suggest that supplementary vitamin C may have adverse consequences in patients receiving cancer therapy" (1). Selectively referring to dehydroascorbic acid as vitamin C throughout the majority of this work may send a clo...
Ascorbic acid is an essential nutrient commonly regarded as an antioxidant. In this study, we showed that ascorbate at pharmacologic concentrations was a prooxidant, generating hydrogen-peroxide-dependent cytotoxicity toward a variety of cancer cells in vitro without adversely affecting normal cells. To test this action in vivo, normal oral tight c...
Ascorbate (ascorbic acid, vitamin C), in pharmacologic concentrations easily achieved in humans by i.v. administration, selectively kills some cancer cells but not normal cells. We proposed that pharmacologic ascorbate is a prodrug for preferential steady-state formation of ascorbate radical (Asc•−) and H2O2 in the extracellular space compared with...
Human pharmacokinetics data indicate that i.v. ascorbic acid (ascorbate) in pharmacologic concentrations could have an unanticipated role in cancer treatment. Our goals here were to test whether ascorbate killed cancer cells selectively, and if so, to determine mechanisms, using clinically relevant conditions. Cell death in 10 cancer and 4 normal c...
For Abstract see ChemInform Abstract in Full Text.
Beta-carboline alkaloids such as harmine are present in medicinal plants such as Peganum harmala that have been used as folk medicine in anticancer therapy. In our study, 9 harmine derivatives (including harmine) were investigated for their antitumor effects and acute toxicities in mice, and the structure-activity relationship (SAR) was also analyz...
A series of novel 1,3-bisubstituted and 1,3,9-trisubstituted beta-carboline derivatives was synthesized from the starting material l-tryptophan. Cytotoxic activities of these compounds were investigated in vitro. The results showed that 1,3,9-trisubstituted beta-carboline derivatives had higher cytotoxic activities in vitro than the corresponding 1...
