Transferrin overcomes drug resistance to artemisinin in human small-cell lung carcinoma cells

Sadava, David; Phillips, Tiphanie; Lin, Cindy; Kane, Susan E.

doi:10.1016/s0304-3835(02)00005-8

Cited by 92 publications

(53 citation statements)

References 20 publications

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“…The overall response rate to systemic chemotherapy for the treatment of HCC is generally less than 10%, owing to drug (36,37). This study represents an effort in searching for natural product anti-HCC agents.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Experimental Therapy of Hepatoma with Artemisinin and Its Derivatives: In vitro and In vivo Activity, Chemosensitization, and Mechanisms of Action

Hou

Wang

Zhang

et al. 2008

Clinical Cancer Research

301

248

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Purpose: ART and its derivatives, clinically used antimalarial agents, have recently shown antitumor activities. However, the mechanisms underlying these activities remain unclear. This study was designed to determine their antitumor efficacy and underlying mechanisms of action in human hepatoma cells. Experimental Design: The in vitro cytotoxicities of ART, DHA, artemether, and artesunate were compared in human hepatoma cells, HepG2 (p53 wild-type), Huh-7 and BEL-7404 (p53 mutant), and Hep3B (p53 null), and a normal human liver cell line, 7702. Based on their activity and specificity, ART and DHA were further investigated for their in vitro and in vivo antitumor effects and their effects on the protein expression of genes associated with cell proliferation and apoptosis. Results: ART and DHA exerted the greatest cytotoxicity to hepatoma cells but significantly lower cytotoxicity to normal liver cells. The compounds inhibited cell proliferation, induced G 1 -phase arrest, decreased the levels of cyclin D1, cyclin E, cyclin-dependent kinase 2, cyclindependent kinase 4, and E2F1, and increased the levels of Cip1/p21 and Kip1/p27. They induced apoptosis, activated caspase-3, increased the Bax/Bcl-2 ratio and poly(ADP-ribose) polymerase, and down-regulated MDM2. In mice bearing HepG2 and Hep3B xenograft tumors, ART and DHA inhibited tumor growth and modulated tumor gene expression consistent with in vitro observations. DHA increased the efficacy of the chemotherapeutic agent gemcitabine. Conclusions: ART and DHA have significant anticancer effects against human hepatoma cells, regardless of p53 status, with minimal effects on normal cells, indicating that they are promising therapeutics for human hepatoma used alone or in combination with other therapies.

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Section: Discussionmentioning

confidence: 99%

“…This study represents an effort in searching for natural product anti-HCC agents. ART and its derivatives inhibit the growth of several types of cancer cells (13 -18), including drug-resistant cell lines (37), suggesting that ART could become the basis of a new class of potent anticancer drugs.…”

Section: Discussionmentioning

confidence: 99%

Experimental Therapy of Hepatoma with Artemisinin and Its Derivatives: In vitro and In vivo Activity, Chemosensitization, and Mechanisms of Action

Hou

Wang

Zhang

et al. 2008

Clinical Cancer Research

301

248

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“…Previous studies have revealed that artemisinin is able to inhibit the progression of chronic myelogenous leukemia, pancreatic adenocarcinoma, colon cancer, prostate cancer, non-small cell lung cancer and breast malignancies at low concentrations (8)(9)(10). Artemisinin and its derivatives have also been used in the screening of anticancer drugs by the National Cancer Institute (NCI) (11).…”

Section: Introductionmentioning

confidence: 99%

Dihydroartemisinin increases temozolomide efficacy in glioma cells by inducing autophagy

et al. 2015

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Abstract. Artemisinin, a powerful antimalarial medicine, is extracted from the Chinese herb, Artemisia annua L., and has the ability to inhibit the proliferation of cancer cells. Dihydroartemisinin (DHA), the major active metabolite of artemisinin, is able to inhibit the growth of a variety of types of human cancer. However, the effect of DHA on human glioma cells remains unclear. The aim of the present study was to investigate the effect of DHA on the proliferation of glioma cells, and whether DHA was able to enhance temozolomide (TMZ) sensitivity in vitro and in vivo. In total, 10 human glioma cell lines were used to analyze the growth inhibition ability of DHA by MTT assay. The typical autophagic vacuoles were monitored by the application of the autofluorescent agent, monodansylcadaverine. Western blotting was used to detect markers of apoptosis and autophagy, namely Caspase-3, Beclin-1 and LC3-B. The combination efficiency of DHA and TMZ was assessed in vitro and in vivo. The half maximal inhibitory concentration (IC 50 ) of DHA differed among the ten human glioma cell lines. The number of autophagic vacuoles was higher in DHA-treated SKMG-4 cells; this was highest of all cell lines analyzed. The expression of autophagy molecular markers, Beclin-1 and LC3-B, was increased following DHA treatment, while no significant alteration was detected in the expression of apoptotic marker Caspase-3. When combined with DHA, the IC 50 of TMZ decreased significantly in the four glioma cell lines analyzed. Furthermore, DHA enhanced the tumor inhibition ability of TMZ in tumor-burdened mice. The results of the present study demonstrated that DHA inhibited the proliferation of glioma cells and enhanced the tumor inhibition efficacy of TMZ in vitro and in vivo through the induction of autophagy.

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“…The cytotoxicity of ART on H69VP cells (IC 50 = 24 nM) was ten-fold lower than for H69 cells (IC 50 = 2.3 nM). Pretreatment with 880 nM holotransferrin did not alter the cytotoxicity of ART on H69 cells, but significantly enhanced the effect on H69VP cells (IC 50 = 5.4 nM) (Sadava et al, 2002). A recent study demonstrated that ART induced cell growth arrest in A375M malignant melanoma tumor cells, and also affected the viability of A375P cutaneous melanoma tumor cells with both cytotoxic and growth inhibitory effects, while ART was not effective in inhibiting growth of other tumor cell lines (MCF7 and MKN).…”

Section: Artemisinin (Art)mentioning

confidence: 86%

Therapeutic and Toxicological Inhibition of Vasculogenesis and Angiogenesis Mediated by Artesunate, a Compound with Both Antimalarial and Anticancer Efficacy

Li¹,

Hickman²,

Weina³

2011

Vasculogenesis and Angiogenesis - From Embryonic Development to Regenerative Medicine

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Transferrin overcomes drug resistance to artemisinin in human small-cell lung carcinoma cells

Cited by 92 publications

References 20 publications

Experimental Therapy of Hepatoma with Artemisinin and Its Derivatives: In vitro and In vivo Activity, Chemosensitization, and Mechanisms of Action

Experimental Therapy of Hepatoma with Artemisinin and Its Derivatives: In vitro and In vivo Activity, Chemosensitization, and Mechanisms of Action

Dihydroartemisinin increases temozolomide efficacy in glioma cells by inducing autophagy

Therapeutic and Toxicological Inhibition of Vasculogenesis and Angiogenesis Mediated by Artesunate, a Compound with Both Antimalarial and Anticancer Efficacy

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