<i>Tegillarca granosa</i>extract Haishengsu inhibits the expression of<i>p</i>-glycoprotein and induces apoptosis in drug-resistant K562/ADM cells

Li, Guangyao; Liu, Jizhu; Chen, Shou-Guo; Zhang, Bin; Wang, Chunbo; Wang, Lexin

doi:10.3109/13880200903176620

Cited by 12 publications

(16 citation statements)

References 9 publications

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“…4 Our recent study also demonstrated that with adriamycin-resistant K562/ADM cells, HSS also increased the rate of apoptosis. 12 In addition, HSS reduced the expressions of pglycoprotein, a drug-resistance inducing protein in leukemia and other cells. 12 These actions may have contributed the anti-tumor effects as observed in the present study.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Haishengsu on transplanted K562 and drug-resistant K562/ADM tumors: An experimental study

Liu

Yang²,

Li³

et al. 2009

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Clin Invest Med 2009; 32 (2): E117-E123. AbstractPurpose: To evaluate the effect of Haishengsu (HSS) on transplanted K562 and drug-resistant K562/ADM tumors. Methods: Mice were inoculated subcutaneously with K562 and K562/ADM cells, respectively. Tumour-bearing animals were divided into HSS, adriamycin, combination therapy (adriamycin plus HSS) and placebo groups. The anti-tumour effect was assessed by tumour growth curve and tumour inhibitory rate (IR). Results: In animals inoculated with K562 cells, the inhibitory rates of high (1800mg/kg) and medium (900mg/kg ) dose HSS groups were 100% and 96.4%, respectively, which was higher than that in the adriamycin (88.9%) or the combination therapy groups (85.8%, P<0.05). The inhibitory rate in the low-dose HSS group (53.4%) was lower than in all other groups (P<0.01). In mice inoculated with K562/ADM cells, the inhibitory rates in the high, medium and low dose HSS groups were 100%, 95.9%, and 44.1%, respectively. In the adriamycin group, the inhibitory rate was 23.07%, which was lower than in the HSS group (P < 0.01). Pathological examination of tumour tissues from HSS-treated animals showed extensive necrosis and bleeding. Conclusions: Haishengsu inhibits the growth of transplanted K562 tumours in mice. It is also effective in suppressing the growth of drug-resistant K562/ADM tumors in this animal model. Tegillarca granosa L. (Chinese name "xue han") is a species of seashell. It is widely distributed and used as a traditional Chinese medicine for cancer treatment in mainland China. Haishengsu (HSS) is a protein extract from Tegillarca granosa with a molecular weight of approximately 15 KDal. HSS has a potent suppressive effect on several types of tumor cells in vivo and

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Section: Discussionmentioning

confidence: 99%

“…12 In addition, HSS reduced the expressions of pglycoprotein, a drug-resistance inducing protein in leukemia and other cells. 12 These actions may have contributed the anti-tumor effects as observed in the present study.…”

Section: Discussionmentioning

confidence: 99%

Effect of Haishengsu on transplanted K562 and drug-resistant K562/ADM tumors: An experimental study

Liu

Yang²,

Li³

et al. 2009

CIM

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“…HSS was also tested against MDR K562/ADR cells, and it induced apoptosis at 20 mg/l [178]. HSS also inhibited K562 cells at G0/G1 and S phase and lowered Bcl-2 and enhanced Bax levels ( Figure 2) (Table 6) [179].…”

Section: Saponinsmentioning

confidence: 98%

Natural Products for Treatment of Chronic Myeloid Leukemia

Khajapeer¹,

Baskaran²

2016

Anti-Cancer Drugs - Nature, Synthesis and Cell

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Chronic myeloid leukemia (CML) is a hematological malignancy that arises due to reciprocal translocation of 3′ sequences from c-Abelson (abl) protooncogene on chromosome 9 with 5′ sequence of truncated break point cluster region (bcr) to chromosome 22. The fusion gene product BCR-ABL, a functional oncoprotein p210, is a constitutively activated tyrosine kinase that activates several cell proliferative signaling pathways. BCR-ABL-specific tyrosine kinase inhibitors (TKIs) such as imatinib, nilotinib and ponatinib potently inhibit CML progression. However, drug resistance owing to BCR-ABL mutations and overexpression is still an issue. Natural products are chemical compounds or substances produced by living organisms. They are becoming an important research area for cancer drug discovery due to their low toxicity and cost-effectiveness. Several lines of evidence show that many NPs such as alkaloids, flavonoids, terpenoids, polyketides, lignans and saponins inhibit CML cell proliferation and induce apoptosis. NPs not only differentiate CML cells into monocyte/erythroid lineage but also can reverse the multi-drug resistance (MDR) in CML cells. In this chapter, we review the anti-CML activity of various NPs.

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“…[4][5][6] The apoptotic proteins of bax and caspase-3 were increased and bcl-2 was decreased in K562 and K562/A02 cells following HSS treatment. 21 HSS has been considered as a potential candidate agent for cancer treatment, and phase I clinical evaluation on several types of cancers is currently underway in China. 19,20 In this study, we evaluated the efficacy of HSS on the proliferation and on the activity of MMP-2 and MMP-9 in human lung carcinoma cells.…”

Section: Inhibition Of A549 Tumor Growth In Micementioning

confidence: 99%

“…For example, most growth factors, including EGF, HB-EGF, TGFα, TNFα, and CSF-1, are sequestered in ECM by virtue of their binding to ECM proteins. [21][22][23][24][25] Highly active MMP-2 and MMP-9 can degrade these binding proteins, liberating the growth Established tumors were treated with HSS as described in "Material and Methods." Body weight was measured before and after drug administration.…”

Section: Inhibition Of A549 Tumor Growth In Micementioning

confidence: 99%

Haishengsu, a Protein from Shellfish Tegillarca L. granosa, Inhibits the Growth and the Activity of Matrix Metalloproteinases-2 and -9 in Human Lung Carcinoma

et al. 2011

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Haishengsu (HSS) is a seashell protein extracted from Tegillarca L. granosa, a type of Malaysian shellfish. Previous in vitro studies showed that HSS might possess biological anticancer activity. In this combined in vitro and in vivo study, we investigated the inhibitory effects of HSS on tumor growth, invasion, and metastasis using human lung carcinoma cell lines A549 and NCI-H292, both intensely positive for matrix metalloproteinases-2 (MMP-2) and MMP-9. HSS significantly inhibited the proliferation of A549 and NCI-H292 as estimated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The transwell chamber assay showed that HSS effectively blocked the invasion and migration of the carcinoma cells through the reconstituted extracellular matrix (Matrigel). Gelatin zymography analysis revealed that the secretion and activity of MMP-2 and MMP-9 in the supernatants of the cultured cells A549 and NCI-H292 were decreased after treatment with HSS. The levels of MMP-2 and MMP-9 in these cancer cells were further examined by Western blot assay in which a significant decrease of MMP-2 and MMP-9 was observed in A549 and NCI-H292 cells after 24 h of exposure to HSS. The anticancer activity of HSS was verified in a mouse model in which HSS delayed the growth of A549 xenografts after 3 weeks of oral administration. Inhibition of MMP-2 and MMP-9 expression was also demonstrated in the A549 xenografts as determined by Western blot analysis. These results suggest that HSS is a novel seashell protein that cannot only inhibit tumor growth but also prevent tumor invasion and metastasis through suppressing the activity of MMP-2 and MMP-9.

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Tegillarca granosaextract Haishengsu inhibits the expression ofp-glycoprotein and induces apoptosis in drug-resistant K562/ADM cells

Cited by 12 publications

References 9 publications

Effect of Haishengsu on transplanted K562 and drug-resistant K562/ADM tumors: An experimental study

Effect of Haishengsu on transplanted K562 and drug-resistant K562/ADM tumors: An experimental study

Natural Products for Treatment of Chronic Myeloid Leukemia

Haishengsu, a Protein from Shellfish Tegillarca L. granosa, Inhibits the Growth and the Activity of Matrix Metalloproteinases-2 and -9 in Human Lung Carcinoma

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