Hai-Yan Tian

Jinan University (Guangzhou, China), Shengcheng, Guangdong, China

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Publications (29)53.98 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Hellebrigenin, one of bufadienolides belonging to cardioactive steroids, was found in skin secretions of toads and plants of Helleborus and Kalanchoe genera. In searching for natural constituents with anti-hepatoma activities, we found that hellebrigenin, isolated from traditional Chinese medicine Venenum Bufonis, potently reduced the viability and colony formation of human hepatocellular carcinoma cells HepG2, and went on to explore the underlying molecular mechanisms. Our results demonstrated that hellebrigenin triggered DNA damage through DNA double-stranded breaks and subsequently induced cell cycle G2/M arrest associated with up-regulation of p-ATM (Ser(1981)), p-Chk2 (Tyr(68)), p-CDK1 (Tyr(15)) and Cyclin B1, and down-regulation of p-CDC25C (Ser(216)). It was also found that hellebrigenin induced mitochondrial apoptosis, characterized by Bax translocation to mitochondria, disruption of mitochondrial membrane potential, release of cytochrome c into cytosol and sequential activation of caspases and PARP. In addition, Akt expression and phosphorylation were inhibited by hellebrigenin, whereas Akt silencing with siRNA significantly blocked cell cycle arrest but enhanced apoptosis induced by hellebrigenin. Activation of Akt by human insulin-like growth factor I (hIGF-I) could obviously attenuate hellebrigenin-induced cell death. In summary, our study is the first to report the efficacy of hellebrigenin against HepG2 and elucidated its molecular mechanisms including DNA damage, mitochondria collapse, cell cycle arrest and apoptosis, which will contribute to the development of hellebrigenin into a chemotherapeutic agent in the treatment of liver cancer.
    Chemico-biological interactions. 06/2014;
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    ABSTRACT: Two new bufadienolide glycosides (1 and 2) with an A/B trans ring fusion together with nine known compounds (3–11) were isolated from the rhizomes of Helleborus thibetanus. The structures of new compounds were elucidated by extensive spectroscopic analyses in combination with single-crystal X-ray diffraction. The bufadienolides 1 and 3–6 exhibited potent cytotoxic activities against the prostate cancer cells.
    Natural Product Research 06/2014; 28(12). · 1.03 Impact Factor
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    ABSTRACT: The title compound, C24H33NO4·H2O, the reaction product of de-acetyl-cinobufagin with ammonium acetate, consists of three cyclo-hexane rings (A, B and C), one five-membered ring (D), one six-membered lactone ring (E) and an epoxide ring (F). The stereochemistry of the ring junctures are A/B cis, B/C trans, C/D cis and D/F cis. Cyclo-hexane rings A, B and C have normal chair conformations. The five-membered ring D adopts an envelope conformation (with the C atom bearing the lactone ring as the flap) and the lactone ring E is planar. In the crystal, hy-droxy and water O-H⋯O and amine N-H⋯O hydrogen bonds involving carbonyl, hy-droxy and water O-atom acceptors link the mol-ecules into a three-dimensional network.
    Acta Crystallographica Section E Structure Reports Online 06/2014; 70(Pt 6):o651-2. · 0.35 Impact Factor
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    ABSTRACT: A new cyclodepsipeptide cordycecin A (1), together with four known ones beauvericin E (2), beauvericin J (3), beauvericin (4), and beauvericin A (5) were isolated from the ascocarps and insect-body portions of fungus Cordyceps cicadae. Their structures were identified by NMR and MS analyses. The absolute configuration of 1 was confirmed by crystal X-ray diffraction. Compounds 2-5 exhibited a significant inhibitory effect on HepG2 and HepG2/ADM cells with IC50 values ranging from 2.40±0.37 to 14.48±1.68μM. Interestingly, compounds 3-5 showed cytotoxic activity against multiple drug resistant HepG2 cell line (HepG2/ADM) with IC50 value 25-fold more sensitive to doxorubicin.
    Fitoterapia 05/2014; · 2.23 Impact Factor
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    ABSTRACT: To investigate the chemical constituents of medicinal plant Uncaria hirsuta, three new monoterpenoid alkaloids, named hirsutanines A-C (1-3), were isolated. Their structures with absolute configurations were elucidated by means of NMR, X-ray diffraction and CD analysis. Compound 3 was the first dimeric monoterpenoid alkaloid obtained from genus Uncaria.
    Natural product research 04/2014; · 1.01 Impact Factor
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    ABSTRACT: Bufalin possesses a strong anti-cancer effect, but the cardiac toxicity targeting the Na(+), K(+)-ATPase limits its application. Here, two bufalin derivatives, bufadienolactam (1) and secobufalinamide (2), were synthesised by treating bufalin with ammonium acetate in dimethylformamide solution. Their structures were elucidated by extensive spectroscopic methods. The structure of compound 2 was further confirmed by single-crystal X-ray diffraction analysis. Compounds 1 and 2 expressed strong inhibitory activities against androgen-dependent prostate cancer cells (IC50 values about 10 μM), but only weak inhibition on Na(+), K(+)-ATPase (Ki about 70 μM), indicating that they might be potential anti-prostate cancer agents without severe cardiac toxicity.
    Natural product research 01/2014; · 1.01 Impact Factor
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    ABSTRACT: Three new C-3 dehydrated bufadienolides (1-3) were isolated from the venom of Bufo bufo gargarizans. Compounds 2 and 3 showed significant cytotoxicities with IC50 values less than 10 μmol/L on A549 and HepG2 cancer cells.
    Chinese Chemical Letters 01/2014; · 1.21 Impact Factor
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    ABSTRACT: One new stenine-type alkaloid, tuberostemonine D (1), together with five known stenine-type alkaloids (2-6) and two known stemoninine-type alkaloids (7 and 8), were isolated from the roots of Stemona tuberosa, which provided chemotaxonomic clues for the close relationship between genera Stemona and Stichoneuron.
    Chinese Chemical Letters 01/2014; · 1.21 Impact Factor
  • Fitoterapia 01/2014; 97:23–27. · 2.23 Impact Factor
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    ABSTRACT: Natural products present in low quantity in herb medicines constitute an important source of chemical diversity. However, the isolation of sufficient amounts of these low abundant constituents for structural modification has been a challenge for several decades and subsequently halts research on the utilization of this important source of chemical entities for drug discovery and development. And, pro-angiogenic therapies are being explored as options to treat cardio-cerebral vascular diseases and wound healing recently. The present study investigates the pro-angiogenic potential of tanshinone derivatives produced by one-pot synthesis using zebrafish model.
    PLoS ONE 01/2014; 9(7):e100416. · 3.73 Impact Factor
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    ABSTRACT: Molecular docking studies have shown that Δ(8,14)-anhydrobufalin (1) exhibited more potent binding affinity on androgen receptor (AR) than Δ(14,15)-anhydrobufalin (2) and bufalin (3). To validate the docking results, compounds 1 and 2 were synthesized. The AR competitive binding assay indicated that the IC50 values of 1-3 were 1.9, >50 and >50 μM (relative binding affinity), respectively, which confirmed that our theoretical binding mode was reliable and predictable. Furthermore, compound 1 was found to show more potent inhibitory activity against the androgen dependent LNCaP cancer cells than the androgen independent PC3 cancer cells, but exhibited less inhibition on the Na(+)/K(+) ATPase as compared with the parent compound 3. To the best of our knowledge, compound 1 represented the first AR antagonist derived from bufadienolide discovered through a series of combined approaches of molecular docking and actual experimental validation.
    Chemico-biological interactions 11/2013; · 2.46 Impact Factor
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    ABSTRACT: Five new C23 steroids (1-5) together with five known bufadienolides (6-10) were isolated from the venom of Bufo bufo gargarizans (ChanSu in Chinese). The structures of the new steroids were elucidated by extensive spectroscopic methods in combination with X-ray diffraction analysis. Among these C23 steroids, only compound 3 showed cytotoxicities against HepG2 and A549 cancer cells, with respective IC50 values of 26.8 ± 8.3 and 45.6 ± 2.5 μM. In contrast, the bufadienolides (7-10) displayed potent inhibitory activities against these cancer cells, with respective IC50 values in the ranges 0.5-5.5 and 0.6-6.5 μM, but relatively less cytotoxicity on normal mouse spleen cells. In addition, the Na(+)/K(+)-ATPase inhibitory activities of 2, 5, and 7 revealed that the lactone moiety of a bufadienolide was important for the inhibitory activity.
    Journal of Natural Products 09/2013; · 3.29 Impact Factor
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    ABSTRACT: Eight new oleanane-type triterpenoid saponins, named schefflesides A-H (1-8), were isolated from the aerial parts of Schefflera kwangsiensis. The structures of these new compounds were established on the basis of hydrolysis and spectroscopic evidence, including 1D- and 2D-NMR (HSQC, HMBC, ROESY and TOCSY) and HR-MS analyses.
    Carbohydrate research 08/2013; 385C:65-71. · 2.03 Impact Factor
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    ABSTRACT: ClC-3 chloride (Cl-) channel has been shown to be involved in cell proliferation, cell cycle and cell migration processes. Herein, we found that a series of bufadienolides isolated from toad venom were a novel class of ClC-3 Cl- channel activators with antitumor activities. Bufalin, which has the most potent antitumor activity, and 15ß-acetyloxybufalin, which has no antitumor activity, were chosen as representative compounds to investigate the role of the ClC-3 Cl- channel. It was found that bufalin rapidly elicited the activation of the ClC-3 Cl- channel and subsequently induced apoptosis through the inhibition of the PI3K/Akt/mTOR pathway. PI3K/Akt/mTOR pathway was strongly attenuated by the pretreatment with Cl- channel blockers (Tamoxifen and NPPB) or ClC-3 siRNA. In summary, we discovered that the activation of ClC-3 Cl- channel, which subsequently induced the inhibition of PI3K/Akt/mTOR signaling pathway, was involved in the antitumor activities of bufadienolides.
    Journal of Medicinal Chemistry 06/2013; · 5.61 Impact Factor
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    ABSTRACT: Two new vinblastine-type N-oxide alkaloids, 17-desacetoxyvinblastine [Formula: see text]-oxide (1) and 20'-deoxyvinblastine [Formula: see text]-oxide (2), were isolated from the leaves of Catharanthus roseus. The structures of 1 and 2 were established by the analysis of their nuclear magnetic resonance and HR-ESI-MS spectroscopic data. All alkaloids were evaluated for their cytotoxic activities against the human hepatocellular carcinoma (HepG2) cell line, human colorectal carcinoma (Lovo) cell line and human breast carcinoma (MCF-7) cell line by the MTT method in vitro, respectively. The results showed that cytotoxic activities of alkaloids 1 and 2 exhibited moderate inhibitory activity on the proliferation of three cancer cells.
    Natural product research 04/2013; · 1.01 Impact Factor
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    ABSTRACT: Hepatocellular carcinoma (HCC) is a deadly form of cancer without effective chemotherapy so far. Currently only sorafenib, a multitargeted tyrosine kinase inhibitor, slightly improves survival in HCC patients. In searching for natural anti-HCC components from toad venom which is frequently used in the treatment of liver cancer in traditional Chinese medicine, we discovered that arenobufagin, a bufadienolide from toad venom, had potent antineoplastic activity against HCC HepG2 cells as well as corresponding multidrug-resistant HepG2/ADM cells. We found that arenobufagin induced mitochondria-mediated apoptosis in HCC cells, with decreasing mitochondrial potential, as well as increasing Bax/Bcl-2 expression ratio, Bax translocation from cytosol to mitochondria. Arenobufagin also induced autophagy in HepG2/ADM cells. Autophagy-specific inhibitors (3-methyladenine, chloroquine, and bafilomycin A1) or Beclin1 and Atg 5 siRNAs enhanced arenobufagin-induced apoptosis, indicating that arenobufagin-mediated autophagy may protect HepG2/ADM cells from undergoing apoptotic cell death. In addition, we observed the inhibition of PI3K/Akt/mTOR pathway by arenobufagin. Interestingly, inhibition of mTOR by rapamycin or siRNA duplexes augmented arenubufagin-induced apoptosis and autophagy. Finally, arenobufagin inhibited the growth of HepG2/ADM xenograft tumors, which were associated with PARP cleavage, LC3-II activation, and mTOR inhibition. In summary, we first demonstrated the antineoplastic effect of arenobufagin on HCC cells both in vitro and in vivo. We elucidated the underlying antineoplastic mechanisms of arenubufagin that involve crosstalk between apoptosis and autophagy via inhibition of the PI3K/Akt/mTOR pathway. This study may provide a rationale for future clinical application using arenobufagin as a chemotherapeutic agent for HCC.
    Carcinogenesis 02/2013; · 5.64 Impact Factor
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    ABSTRACT: The title compound, C22H29NO4, a stemona alkaloid, is composed of two lactone rings (A and E), a six-membered ring (B), a pyrrole ring (C) and a seven-membered ring (D). The five-membered rings A and E exhibit envelope conformations (C atoms as flaps) while ring C is planar. Ring B exhibits a twist-chair conformation due to fusion with pyrrole ring C while ring D adopts a chair conformation. The junction between rings A and B is cis. In the crystal, weak C-H⋯O inter-actions involving the two carbonyl groups, a methyl-ene and a methyl group give rise to a three-dimensional network.
    Acta Crystallographica Section E Structure Reports Online 01/2013; 69(Pt 9):o1369-70. · 0.35 Impact Factor
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    ABSTRACT: Podophyllotoxin (POD) is a naturally occurring lignan with pronounced antineoplastic and antiviral properties. POD binds to tubulin and prevents the formation of mitotic spindle. Although cases of overdose or accidental ingestion are quite often, no specific therapy is currently available to treat the POD intoxication. In the current investigation, the protective effects and mechanisms of curcumin (CUR) on podophyllotoxin toxicity were evaluated in vitro and in vivo. The results showed that CUR could protect POD-induced cytotoxicity by recovering the G2/M arrest and decrease the changes of membrane potential and microtubule structure in Vero cells. A significant decrease of mortality rates was observed in Swiss mice treated by intragastrical administration of POD+CUR as compared with POD alone. The POD+CUR group also exhibited decreases in plasma transaminases, alkaline phosphatase, lactate dehydrogenase, plasma urea, creatinine and malondialdehyde level but elevated superoxide dismutase and glutathione level as compared to the POD group. Histological examination of the liver and kidney demonstrated less morphological changes in the treatment of POD+CUR as compared with POD alone. The mechanism of the protective effects might be due to the competitive binding of CUR with POD in the same colchicines binding site as revealed by the tubulin polymerization assay and the molecular docking analysis, and the antioxidant activity against the oxidative stress induced by POD. In summary, both in vitro and in vivo data indicated the promising role of CUR as a protective agent against the POD poisoning.
    Toxicology and Applied Pharmacology 10/2012; · 3.98 Impact Factor
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    ABSTRACT: Venenum Bufonis, a traditional Chinese medicine, is widely used in the treatment of liver cancer in modern Chinese medical practices. In our search for anti-hepatoma constituents in Venenum Bufonis, bufotalin, bufalin, telocinobufagin and cinobufagin were obtained. Bufotalin was the most potent active compound among these four bufadienolides, and it exerted stronger inhibitory effect on the viability of doxorubicin-induced multidrug resistant liver cancer cells (R-HepG2) than that of their parent cells HepG2. Structure-activity relationship analysis indicated that the acetyl group linked to C-16 of bufadienolides might be useful for increasing anti-hepatoma activity. Further mechanistic studies revealed that bufotalin treatment induced cell cycle arrest at G(2)/M phase through down-regulation of Aurora A, CDC25, CDK1, cyclin A and cyclin B1, as well as up-regulation of p53 and p21. Bufotalin treatment also induced apoptosis which was accompanied by decrease in mitochondrial membrane potential, increases in intracellular calcium level and reactive oxygen species production, activations of caspase-9 and -3, cleavage of poly ADP-ribose polymerase (PARP) as well as changes in the expressions of bcl-2 and bax. It was also found that the inhibition of Akt expression and phosphorylation was involved in apoptosis induction, and specific Akt inhibitor LY294002 or siRNA targeting Akt can synergistically enhanced bufotalin-induced apoptosis. In vivo study showed that bufotalin significantly inhibited the growth of xenografted R-HepG2 cells, without body weight loss or marked toxicity towards the spleen. These results indicate that bufotalin has a promising potential to become a novel anti-cancer agent for the treatment of liver cancer with multidrug resistance.
    European journal of pharmacology 07/2012; 692(1-3):19-28. · 2.59 Impact Factor
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    ABSTRACT: The title compound, C(24)H(30)O(5), is the didehydro product of the steroid hellebrigenin (systematic name: 3β,5,14-trihy-droxy-19-oxo-5β-bufa-20,22-dienolide). It consists of three cyclo-hexane rings (A, B and C), a five-membered ring (D) and a six-membered lactone ring (E). The stereochemistry of the ring junctions are A/B cis, B/C trans and C/D cis. Cyclo-hexane rings A, B and C have normal chair conformations. The five-membered ring D with the C=C bond adopts an envelope conformation. Lactone ring E is essentially planar with a mean derivation of 0.006 (4) Å and is β-oriented at the C atom of ring D to which it is attached. There is an O-H⋯O hydrogen bond in the mol-ecule involving the hy-droxy groups. In the crystal, O-H⋯O hydrogen bonds link the mol-ecules into chains propagating along [010]. The chains are linked by C-H⋯O contacts into a three-dimensional network.
    Acta Crystallographica Section E Structure Reports Online 06/2012; 68(Pt 6):o1614-5. · 0.35 Impact Factor

Publication Stats

25 Citations
53.98 Total Impact Points

Institutions

  • 2010–2014
    • Jinan University (Guangzhou, China)
      • School of Medicine
      Shengcheng, Guangdong, China
    • University of Jinan (Jinan, China)
      Chi-nan-shih, Shandong Sheng, China
    • China Pharmaceutical University
      • Department of Phytochemistry
      Nan-ching-hsü, Jiangxi Sheng, China
  • 2013
    • China-Japan Friendship Hospital
      Peping, Beijing, China