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Total alkaloids of Rubus aleaefolius Poir inhibit hepatocellular carcinoma growth in vivo and in vitro via activation of mitochondrial-dependent apoptosis.
Int J Oncol. 2013 Mar; 42(3):971-8.IJ

Abstract

The aim of this study was to evaluate the therapeutic efficacy of Rubus aleaefolius Poir total alkaloids (TARAP) against hepatocellular carcinoma growth in vivo and in vitro, and to investigate the possible molecular mechanisms mediating its biological activity. Nude mice were implanted with HepG2 human hepatocellular carcinoma cells and fed with vehicle (physiological saline) or 3 g/kg/d dose of TARAP, 5 days per week, for 21 days. The in vivo efficacy of TARAP against tumor growth was investigated by evaluating its effect on tumor volume and tumor weight in mice with HCC xenografts and its adverse effect was determined by measuring the body weight gain. The in vitro effect of TARAP on the viability of HepG2 cells was determined by MTT assay. HepG2 cell morphology was observed via phase-contrast microscopy. Apoptosis in tumor tissues or in HepG2 cells was analyzed by TUNEL assay or FACS analysis with Annexin V/PI, respectively. The loss of mitochondrial membrane potential in HepG2 cells was determined via JC-1 staining followed by FACS analysis. Activation of caspase-9 and -3 in HepG2 cells was examined by a colorimetric assay. The mRNA and protein expression of Bcl-2 and Bax in tumor tissues were measured by RT-PCR and immunohistochemistry. TARAP reduced tumor volume and tumor weight, but had no effect on the body weight gain in HCC mice. TARAP decreased the viability of HepG2 cells and induced cell morphological changes in vitro in a dose- and time-dependent manner. In addition, TARAP induced apoptosis both in tumor tissues and in HepG2 cells. Moreover, TARAP treatment resulted in the collapse of mitochondrial membrane potential in HepG2 cells, as well as the activation of caspase-9 and -3. Furthermore, administration of TARAP increased the pro-apoptotic Bax/Bcl-2 ratio in HCC mouse tumors, at both transcriptional and translational levels. TARAP inhibits hepatocellular carcinoma growth both in vivo and in vitro probably through the activation of mitochondrial-dependent apoptosis, which may, in part, explain its anticancer activity. These results suggest that total alkaloids in Rubus aleaefolius Poir may be a potential novel therapeutic agent for the treatment of hepatocellular carcinoma and other cancers.

Authors+Show Affiliations

Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23338043

Citation

Zhao, Jinyan, et al. "Total Alkaloids of Rubus Aleaefolius Poir Inhibit Hepatocellular Carcinoma Growth in Vivo and in Vitro Via Activation of Mitochondrial-dependent Apoptosis." International Journal of Oncology, vol. 42, no. 3, 2013, pp. 971-8.
Zhao J, Chen X, Lin W, et al. Total alkaloids of Rubus aleaefolius Poir inhibit hepatocellular carcinoma growth in vivo and in vitro via activation of mitochondrial-dependent apoptosis. Int J Oncol. 2013;42(3):971-8.
Zhao, J., Chen, X., Lin, W., Wu, G., Zhuang, Q., Zhong, X., Hong, Z., & Peng, J. (2013). Total alkaloids of Rubus aleaefolius Poir inhibit hepatocellular carcinoma growth in vivo and in vitro via activation of mitochondrial-dependent apoptosis. International Journal of Oncology, 42(3), 971-8. https://doi.org/10.3892/ijo.2013.1779
Zhao J, et al. Total Alkaloids of Rubus Aleaefolius Poir Inhibit Hepatocellular Carcinoma Growth in Vivo and in Vitro Via Activation of Mitochondrial-dependent Apoptosis. Int J Oncol. 2013;42(3):971-8. PubMed PMID: 23338043.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Total alkaloids of Rubus aleaefolius Poir inhibit hepatocellular carcinoma growth in vivo and in vitro via activation of mitochondrial-dependent apoptosis. AU - Zhao,Jinyan, AU - Chen,Xuzheng, AU - Lin,Wei, AU - Wu,Guangwen, AU - Zhuang,Qunchuan, AU - Zhong,Xiaoyong, AU - Hong,Zhenfeng, AU - Peng,Jun, Y1 - 2013/01/18/ PY - 2012/11/05/received PY - 2012/12/20/accepted PY - 2013/1/23/entrez PY - 2013/1/23/pubmed PY - 2013/7/17/medline SP - 971 EP - 8 JF - International journal of oncology JO - Int J Oncol VL - 42 IS - 3 N2 - The aim of this study was to evaluate the therapeutic efficacy of Rubus aleaefolius Poir total alkaloids (TARAP) against hepatocellular carcinoma growth in vivo and in vitro, and to investigate the possible molecular mechanisms mediating its biological activity. Nude mice were implanted with HepG2 human hepatocellular carcinoma cells and fed with vehicle (physiological saline) or 3 g/kg/d dose of TARAP, 5 days per week, for 21 days. The in vivo efficacy of TARAP against tumor growth was investigated by evaluating its effect on tumor volume and tumor weight in mice with HCC xenografts and its adverse effect was determined by measuring the body weight gain. The in vitro effect of TARAP on the viability of HepG2 cells was determined by MTT assay. HepG2 cell morphology was observed via phase-contrast microscopy. Apoptosis in tumor tissues or in HepG2 cells was analyzed by TUNEL assay or FACS analysis with Annexin V/PI, respectively. The loss of mitochondrial membrane potential in HepG2 cells was determined via JC-1 staining followed by FACS analysis. Activation of caspase-9 and -3 in HepG2 cells was examined by a colorimetric assay. The mRNA and protein expression of Bcl-2 and Bax in tumor tissues were measured by RT-PCR and immunohistochemistry. TARAP reduced tumor volume and tumor weight, but had no effect on the body weight gain in HCC mice. TARAP decreased the viability of HepG2 cells and induced cell morphological changes in vitro in a dose- and time-dependent manner. In addition, TARAP induced apoptosis both in tumor tissues and in HepG2 cells. Moreover, TARAP treatment resulted in the collapse of mitochondrial membrane potential in HepG2 cells, as well as the activation of caspase-9 and -3. Furthermore, administration of TARAP increased the pro-apoptotic Bax/Bcl-2 ratio in HCC mouse tumors, at both transcriptional and translational levels. TARAP inhibits hepatocellular carcinoma growth both in vivo and in vitro probably through the activation of mitochondrial-dependent apoptosis, which may, in part, explain its anticancer activity. These results suggest that total alkaloids in Rubus aleaefolius Poir may be a potential novel therapeutic agent for the treatment of hepatocellular carcinoma and other cancers. SN - 1791-2423 UR - https://www.unboundmedicine.com/medline/citation/23338043/Total_alkaloids_of_Rubus_aleaefolius_Poir_inhibit_hepatocellular_carcinoma_growth_in_vivo_and_in_vitro_via_activation_of_mitochondrial_dependent_apoptosis_ L2 - http://www.spandidos-publications.com/ijo/42/3/971 DB - PRIME DP - Unbound Medicine ER -