Mechanistic insight into a novel synthetic cantharidin analogue in a leukaemia model

Kok, Stanton Hon Lung; Chui, Chung Hin; Lam, William W. Y.; Chen, Jien; Lau, Fung Yi; Wong, Raymond Siu Ming; Cheng, Gregory Yin Ming; Tang, Wing Ka; Cheng, Chor Hing; Tang, Johnny Cheuk On; Chan, Albert S. C.

doi:10.3892/ijmm.18.2.375

Cited by 9 publications

(7 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…or M. cichoril L.) has been used in traditional Chinese medicine for the treatment of malignant tumors by its main content cantharidin for more than 1000 years. Norcantharidin (NCTD, (1S,2R,3S,4R)-7-oxabicyclo- [2,2,1] heptane-2,3-dicarboxylic anhydride), the demethylated analogue of cantharidin, inhibits the proliferation of a variety of human tumor cell lines [1][2][3][4][5][6][7][8][9][10][11], and appears to cause the least nephrotoxic and inflammatory side effects. Moreover, NCTD is not a substrate for the P-glycoprotein pump, a known mechanism for developing cancer resistance [6,7].…”

Section: Introductionmentioning

confidence: 99%

“…Norcantharidin (NCTD, (1S,2R,3S,4R)-7-oxabicyclo- [2,2,1] heptane-2,3-dicarboxylic anhydride), the demethylated analogue of cantharidin, inhibits the proliferation of a variety of human tumor cell lines [1][2][3][4][5][6][7][8][9][10][11], and appears to cause the least nephrotoxic and inflammatory side effects. Moreover, NCTD is not a substrate for the P-glycoprotein pump, a known mechanism for developing cancer resistance [6,7]. It is noteworthy that NCTD can stimulate the bone marrow and increase the peripheral white blood cell significantly [12], which makes it more valuable in combination chemotherapy since most of the chemotherapeutic agents in use today have the side effect of bone marrow suppression.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Separation and identification of norcantharidin metabolites in vivo by GC–MS method

Wei¹,

Teng²,

Wang³

et al. 2011

Journal of Chromatography B

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Separation and identification of norcantharidin metabolites in vivo by GC–MS method

Wei¹,

Teng²,

Wang³

et al. 2011

Journal of Chromatography B

View full text Add to dashboard Cite

“…Examples include vanadium, chromium and iron. When concerning vanadium, Lampronti et al discovered that vanadium (V) and (IV) complexes including NaVO 3 2 .H 2 O were all antiproliferative towards K562 CML cells, when administered for 96 h at concentrations ranging from 15-1500 μM. Inhibition of K562 cell growth was not associated with erythroid differentiation, but with activation of apoptosis (8).…”

Section: Discussionmentioning

confidence: 99%

Paradoxical proliferative potential of iron (II) sulphate on cancer cells after the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay

et al. 2007

Self Cite

View full text Add to dashboard Cite

“…4) The main antitumor compound of MB, cantharidin, showed cyto- toxic activity on Hep3B hepatocellular carcinoma. 12) Why does an insect aphid have significant amount of cytotoxic compounds against human leukemia? One possibility is that these compounds might be products from a symbiotic bacteria, Buchnera, because the structures of H373 nor H427 seem not to be from eukariotes, and almost all aphid species (Homoptera, Insecta) have 60-80 huge cells called bacteriocytes, within which there are round-shaped bacteria that are designated Buchnera.…”

Section: Discussionmentioning

confidence: 99%

Pigments from Uroleucon nigrotuberculatum Induce Apoptosis in HL60 Human Leukemia Cells, Implicating Intracellular Oxidative Stress and Activation of Caspases

Suzuki

Tomita

Hyodo

et al. 2006

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

2383Many antitumor antibiotics are derived from natural sources such as bacteria, animals and plants, 1,2) while only a few antitumor seeds from insect sources are known, 3,4) probably because few screening approaches have been performed on insects. Therefore, it is significantly important to identify antitumor agents from insects, which may harbor new compounds with certain antitumor effects via unknown antitumor mechanisms.Apoptosis is essential for normal development and the maintenance of homeostasis. It is a highly regulated cellular process with characteristic morphological and biochemical features. Caspases are a highly conserved cysteine protease family involved in both the commitment and execution phases of apoptosis, resulting in cleavage of specific substrate proteins.5) Two categories of apoptosis have been recognized: initiators and executors. Initiator caspases, which include caspase-8, -9, and -10, are activated in the earlier phase of apoptosis. Executor caspases, which include caspases-3, -6, and -7, are activated by initiator caspases and are responsible for dismantling cells.6,7) Caspase-3 activation, an essential event in apoptosis, is triggered by various stimuli. Caspase-3 cleaves many cytoskeletal proteins, such as fordin, and proteins involved in DNA repair and fragmentation, such as poly-(ADP-ribose) polymerase and DNA fragmentation factor-45. Two pathways lead to the activation of caspase-3 through the release of cytochrome c and cleavage of caspase-9, and through the ligation of death receptors by tumor necrosis factor and Fas ligand. In the pathway stimulated by TNF and Fas ligand, procaspase-8 is recruited and activated by the adaptor molecules FADD/MORT1. Caspase-8 directly activates procaspase-3 and cleaves BID, a member of Bcl-2 family proteins. Apoptosis implicates also reactive oxygen species (ROS)-dependent mechanisms. Increased production of ROS has been recognized as a critical factor in cancer; thus, in cancer cells, ROS may play a role in the stimulation of cellular proliferation, promotion of mutations and genetic instability.8) It is known that oxidative stress triggers the activation and nuclear translocation of p53, and p53-induced apoptosis involves the generation of ROS. 9)Since the apoptotic pathway is a very efficient process in cell death, compounds specifically affecting the key factors in apoptosis could be useful antitumor agents. As has been described above, among the caspases, caspase-8 and caspase-9 are known as initiator caspases, which are activated in the earlier phase of apoptosis. Therefore, the dependency of these two caspases on the apparent feature of 'apoptotic' cell death by the pigments are important factors in order to confirm that these pigments-induced cell death are apoptosis. We thus investigated apoptosis induced by aphid pigments with regard to the implication of ROS and two initiator caspases, caspase-8 and caspase-9. MATERIALS AND METHODSMaterials HL60 cells, a human leukemia cell line, were obtained from the Cancer Cell Repository, Tohoku...

show abstract

Mechanistic insight into a novel synthetic cantharidin analogue in a leukaemia model

Cited by 9 publications

References 8 publications

Separation and identification of norcantharidin metabolites in vivo by GC–MS method

Separation and identification of norcantharidin metabolites in vivo by GC–MS method

Paradoxical proliferative potential of iron (II) sulphate on cancer cells after the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay

Pigments from Uroleucon nigrotuberculatum Induce Apoptosis in HL60 Human Leukemia Cells, Implicating Intracellular Oxidative Stress and Activation of Caspases

Contact Info

Product

Resources

About