SH003 represses tumor angiogenesis by blocking VEGF binding to VEGFR2

Choi, Ha Na; Kim, Min Kyoung; Lee, Kangwook; Lee, Kangmin; Choi, Youn Kyung; Shin, Yong Cheol; Cho, Sung Gook; Ko, Seong‐Gyu

doi:10.18632/oncotarget.8808

Cited by 33 publications

(35 citation statements)

References 45 publications

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“…SH003 is a modified traditional herbal medicine that we have recently developed and used to inhibit breast cancer growth and metastasis [24, 30–32]. Our present findings demonstrate that SH003 can also cause the apoptotic cell death of prostate cancer cells.…”

Section: Discussionsupporting

confidence: 60%

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SH003 induces apoptosis of DU145 prostate cancer cells by inhibiting ERK-involved pathway

Choi

Lee

et al. 2016

BMC Complement Altern Med

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BackgroundHerbal medicines have been used in cancer treatment, with many exhibiting favorable side effect and toxicity profiles compared with conventional chemotherapeutic agents. SH003 is a novel extract from Astragalus membranaceus, Angelica gigas, and Trichosanthes Kirilowii Maximowicz combined at a 1:1:1 ratio that impairs the growth of breast cancer cells. This study investigates anti-cancer effects of SH003 in prostate cancer cells.MethodsSH003 extract in 30% ethanol was used to treat the prostate cancer cell lines DU145, LNCaP, and PC-3. Cell viability was determined by MTT and BrdU incorporation assays. Next, apoptotic cell death was determined by Annexin V and 7-AAD double staining methods. Western blotting was conducted to measure protein expression levels of components of cell death and signaling pathways. Intracellular reactive oxygen species (ROS) levels were measured using H2DCF-DA. Plasmid-mediated ERK2 overexpression in DU145 cells was used to examine the effect of rescuing ERK2 function. Results were analyzed using the Student’s t-test and P-values < 0.05 were considered to indicate statistically-significant differences.ResultsOur data demonstrate that SH003 induced apoptosis in DU145 prostate cancer cells by inhibiting ERK signaling. SH003 induced apoptosis of prostate cancer cells in dose-dependent manner, which was independent of androgen dependency. SH003 also increased intracellular ROS levels but this is not associated with its pro-apoptotic effects. SH003 inhibited phosphorylation of Ras/Raf1/MEK/ERK/p90RSK in androgen-independent DU145 cells, but not androgen-dependent LNCaP and PC-3 cells. Moreover, ERK2 overexpression rescued SH003-induced apoptosis in DU145 cells.ConclusionsSH003 induces apoptotic cell death of DU145 prostate cancer cells by inhibiting ERK2-mediated signaling.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1490-5) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 60%

“…We have also recently shown that SH003 inhibits VEGFR phosphorylation in VEGF-stimulated endothelial cells [32]. Moreover, SH003 also reduces EGFR phosphorylation in MDA-MB-231 breast cancer cells.…”

Section: Discussionmentioning

confidence: 91%

SH003 induces apoptosis of DU145 prostate cancer cells by inhibiting ERK-involved pathway

Choi

Lee

et al. 2016

BMC Complement Altern Med

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“…Whether the activation of p62 disrupts the Nrf1/Keap1-mediated antioxidant mechanism remains to be investigated. Additionally, previous studies indicated that the silencing of p62 suppressed ROS generation, suggesting that p62 accumulation is related to ROS generation [64][65][66][67]. The current study showed that IAp induced T-47D cell apoptosis and autophagy via cellular Nrf1/Keap1 antioxidant depletion and ROS accumulation ( Figures 6B and 8D,E).…”

Section: Discussionsupporting

confidence: 68%

Isoaaptamine Induces t-47D Cells Apoptosis and Autophagy via Oxidative Stress

Shih

et al. 2017

65th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA 2017)

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Abstract:Aaptos is a genus of marine sponge which belongs to Suberitidae and is distributed in tropical and subtropical oceans. Bioactivity-guided fractionation of Aaptos sp. methanolic extract resulted in the isolation of aaptamine, demethyloxyaaptamine, and isoaaptamine. The cytotoxic activity of the isolated compounds was evaluated revealing that isoaaptamine exhibited potent cytotoxic activity against breast cancer T-47D cells. In a concentration-dependent manner, isoaaptamine inhibited the growth of T-47D cells as indicated by short-(MTT) and long-term (colony formation) anti-proliferative assays. The cytotoxic effect of isoaaptamine was mediated through apoptosis as indicated by DNA ladder formation, caspase-7 activation, XIAP inhibition and PARP cleavage. Transmission electron microscopy and flow cytometric analysis using acridine orange dye indicated that isoaaptamine treatment could induce T-47D cells autophagy. Immunoblot assays demonstrated that isoaaptamine treatment significantly activated autophagy marker proteins such as type II LC-3. In addition, isoaaptamine treatment enhanced the activation of DNA damage (γH2AX) and ER stress-related proteins (IRE1 α and BiP). Moreover, the use of isoaaptamine resulted in a significant increase in the generation of reactive oxygen species (ROS) as well as in the disruption of mitochondrial membrane potential (MMP). The pretreatment of T-47D cells with an ROS scavenger, N-acetyl-L-cysteine (NAC), attenuated the apoptosis and MMP disruption induced by isoaaptamine up to 90%, and these effects were mediated by the disruption of nuclear factor erythroid 2-related factor 2 (Nrf 2)/p62 pathway. Taken together, these findings suggested that the cytotoxic effect of isoaaptamine is associated with the induction of apoptosis and autophagy through oxidative stress. Our data indicated that isoaaptamine represents an interesting drug lead in the war against breast cancer.

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“…Previous studies have reported on the use of traditional herbal medicines as alternative cancer therapies (6)(7)(8), including a number of studies on HeLa cervical cancer cells that used herbal medicines as therapeutic agents and compounds for potentially treating cervical cancer (9)(10)(11). Our previous study developed a new herbal medicine, called SH003, which is composed of Astragalus membranaceus (Am), Angelica gigas (Ag) and Trichosanthes kirilowii Maximowicz (Tk), based on the principles of traditional Chinese medicine (12,13). Am and Ag have been reported to be effective treatments for a number of diseases, including hematologic diseases, endocrine disorders and cancers (14)(15)(16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

SH003-induced G1 phase cell cycle arrest induces apoptosis in HeLa cervical cancer cells

Lee

Choi

et al. 2017

Molecular Medicine Reports

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Cervical cancer is a prevalent disease that may lead to mortality in women. In spite of the development of common therapeutic agents to treat cancer, there are several limitations of their use owing to side effects and drug resistance, which may induce cancer recurrence. The anticancer effects of the new herbal mixture SH003 (comprising Astragalus membranaceus, Angelica gigas and Trichosanthes kirilowii Maximowicz) have been examined in various types of cancer. Thus, the present study hypothesized that SH003 may be an effective treatment for cervical cancer. SH003 treatment inhibited the growth of HeLa cells, whereas it did not affect the growth of rat intestinal epithelial cells. In addition, SH003 treatment increased the expression of apoptosis‑related proteins and promoted apoptotic cell death in HeLa cells. SH003 treatment also led to G1 phase arrest in HeLa cells. Furthermore, SH003 treatment induced the production of reactive oxygen species (ROS); however, ROS production did not appear to be related to SH003‑mediated apoptosis. Results from the present study indicated that the SH003‑induced inhibition of HeLa cell growth may be mediated through G1 phase arrest and extrinsic apoptosis, suggested that SH003 may be a potential treatment for cervical cancer.

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SH003 represses tumor angiogenesis by blocking VEGF binding to VEGFR2

Cited by 33 publications

References 45 publications

SH003 induces apoptosis of DU145 prostate cancer cells by inhibiting ERK-involved pathway

SH003 induces apoptosis of DU145 prostate cancer cells by inhibiting ERK-involved pathway

Isoaaptamine Induces t-47D Cells Apoptosis and Autophagy via Oxidative Stress

SH003-induced G1 phase cell cycle arrest induces apoptosis in HeLa cervical cancer cells

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