Antitumor efficacy of lidamycin on hepatoma and active moiety of its molecule

Huang, Yunhong; Shang, Bo-Yang; Zhen, Yong‐Su

doi:10.3748/wjg.v11.i26.3980

Cited by 33 publications

(28 citation statements)

References 8 publications

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“…It is well known that DSB is the most severe DNA lesion, which may explain the highly potent cytotoxicity of LDM toward cancer cells. LDM shows extremely potent cytotoxicity, anti-angiogenic activity and a marked inhibition of transplantable tumors in mice [9][10][11] . The LDM molecule contains an enediyne chromophore (M r 843 Da) responsible for the extremely potent bioactivity and a noncovalently bound apoprotein (M r 10.5 kDa), which forms a hydrophobic pocket for protecting the chromophore [12] .…”

Section: Introductionmentioning

confidence: 99%

Lidamycin shows highly potent cytotoxic to myeloma cells and inhibits tumor growth in mice

Lin

Zhen

2009

Acta Pharmacol Sin

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Aim: To investigate the effects of lidamycin (LDM) on a mouse myeloma cell line (SP2/0) and human multiple myeloma cell lines , and provide the basis for the use of LDM in cancer therapy.-tetrazolium inner salt (MTS) assay was used to determine the degree of growth inhibition by the drugs analyzed in this study. Cell cycle distribution and analysis were measured by flow cytometry combined with propidium iodide (PI) staining. The effects on apoptosis were measured by Hoechst 33342 staining and by flow cytometry combined with fluorescein-isothiocyanate-Annexin V/propidium iodide (FITC-Annexin V/PI) staining. Protein expression was determined by Western blot analysis. In vivo antitumor activity was measured using a murine myeloma model in BALB/c mice.Results: There was a significant reduction in cell proliferation after treatment with LDM. The overall growth inhibition correlated with increased apoptotic cell death. LDM-induced cell apoptosis was associated with the activation of c-Jun-N-terminal kinase (JNK), and cleavage of caspase-3/7 and poly (ADP-ribose) polymerase (PARP). LDM markedly suppressed tumor growth in a murine myeloma model. Conclusion: LDM induces apoptosis in murine myeloma SP2/0 cells as well as in human myeloma U266 and SKO-007 cell lines. The sustained activation of JNK might play a critical role in LDM-induced apoptosis in the SP2/0 cell line. LDM demonstrates significant antitumor efficacy against myeloma SP2/0 cells in mice. Taken together, our data provide some clues for further research of the effects of LDM on human multiple myeloma.

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Section: Introductionmentioning

confidence: 99%

Lidamycin shows highly potent cytotoxic to myeloma cells and inhibits tumor growth in mice

Lin

Zhen

2009

Acta Pharmacol Sin

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“…Lidamycin (LDM, also named as C-1027) is a member of the enediyne antibiotic family, which was produced by a Streptomyces (12,13). LDM shows extremely potent cytotoxicity, anti-angiogenic activity and a marked growth inhibition of transplantable tumors in mice (14)(15)(16)(17). The LDM molecule contains an enediyne chromophore (MW 843 Da) responsible for the extremely potent bioactivity and a noncovalently bound apoprotein (MW 10.5 kDa), which forms a hydrophobic pocket for protecting the chromophore (18,19).…”

Section: Introductionmentioning

confidence: 99%

Down-regulation of the nuclear factor-κB by lidamycin in association with inducing apoptosis in human pancreatic cancer cells and inhibiting xenograft growth

Chen

Ouyang²,

Zhang³

et al. 2007

Oncol Rep

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Abstract. Pancreatic cancer is now one of the most common causes of cancer death worldwide. K-ras mutations are present in up to 90% of pancreatic cancer cases. The expression of mutant K-ras activates the Akt/protein kinase B pathway, resulting in the activation of the nuclear factor-κB (NF-κB) transcriptional factor. Constitutive NF-κB activity plays a key role in pancreatic carcinoma. NF-κB has been shown to inhibit apoptosis in response to chemotherapeutic agents. In the present study, the effects of lidamycin (LDM), a member of the enediyne antibiotic family, were investigated on two established pancreatic cell lines, PANC-1 and SW1990. A dose-dependent inhibition of phospho-Akt and NF-κB activation was found in the cells treated with LDM as determined by Western blot analysis. Moreover, a downregulation of K-ras mRNA and a protein expression by LDM were observed in both cell lines as determined by reverse transcription-PCR and Western blot analysis. By MTT assay, a remarkable difference in chemosensitivity to LDM, mitomycin, adriamycin, taxol, and gemcitabine was found in both cell lines. The IC 50 values of LDM for the PANC-1 or SW1990 cells were 0.955±0.414 or 0.426±0.212 nM, respectively, lower than those of the other drugs. Growth inhibition, apoptosis induction and cell cycle arrest were observed in the LDMtreated cells. LDM decreased the invasive potential of pancreatic cancer cells by reducing matrix metalloproteinase-9 activity. Furthermore, LDM was found to suppress the growth of SW1990 xenografts in nude mice. Treatment with an i.v. injection of LDM at the dose of 0.02 and 0.04 mg/kg (once a week for two weeks) inhibited the growth of xenografts by 66 and 72%, respectively. By contrast, an i.p. injection of gemcitabine at the dose of 80 mg/kg inhibited the growth of xenografts by 38%. Our findings suggest that LDM is active in the down-regulation of NF-κB and could play a positive role in relevant targeted chemotherapy for pancreatic carcinoma.

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“…As an enediyne anticancer antibiotic, LDM showed extremely potent cytotoxicity toward cultured cancer cells and markedly inhibited the growth of transplantable tumors in mice [30][31][32]. LDM (C1027) also showed antiangiogenesis and antimetastatic activity, preferentially targeting hypoxic cells [14].…”

Section: Discussionmentioning

confidence: 99%

Lidamycin inhibits tumor growth and pulmonary metastasis in murine breast carcinoma and shows synergy with paclitaxel

Zhang

Shao

et al. 2013

Chin. Sci. Bull.

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The main goal of this study was to investigate whether lidamycin (LDM) could enhance the efficacy of paclitaxel (TAX) against breast cancer. In the MTT assay, LDM showed much more potent cytotoxicity than paclitaxel, and there was a synergy on the 4T1/luc breast cancer cells treated with a combination of paclitaxel and LDM. Western blot analysis showed that paclitaxel and LDM synergistically downregulated MMP9, MMP2, VEGF, and upregulated the cleaved PARP proteins. By wound closure cell migration assay, paclitaxel combined LDM obviously inhibited the migration of 4T1/luc cells. At therapeutic dosage level, LDM, paclitaxel, and the combination suppressed the pulmonary metastases by 70.2%, 53.8%, and 88.7%, respectively, and the CDI value was 0.82, indicating synergism. The results show that LDM enhances the antitumor effect of paclitaxel on 4T1/luc breast cancer, in particular, the antimetastatic effects on pulmonary metastasis. lidamycin, paclitaxel, breast cancer, antitumor, antimetastatic Citation:Hu L, Zhang S H, Shao R G, et al. Lidamycin inhibits tumor growth and pulmonary metastasis in murine breast carcinoma and shows synergy with paclitaxel.

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Antitumor efficacy of lidamycin on hepatoma and active moiety of its molecule

Abstract: Both LDM and its chromophore LDC display extremely potent cytotoxicity to hepatoma cells. LDM shows a remarkable therapeutic efficacy against murine and human hepatomas in vivo.

Cited by 33 publications

References 8 publications

Lidamycin shows highly potent cytotoxic to myeloma cells and inhibits tumor growth in mice

Lidamycin shows highly potent cytotoxic to myeloma cells and inhibits tumor growth in mice

Down-regulation of the nuclear factor-κB by lidamycin in association with inducing apoptosis in human pancreatic cancer cells and inhibiting xenograft growth

Lidamycin inhibits tumor growth and pulmonary metastasis in murine breast carcinoma and shows synergy with paclitaxel

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