Synergy of Taxol and rhein lysinate associated with the downregulation of ERK activation in lung carcinoma cells

Zhen, Yong‐Su; Hu, Gang; Zhao, Yufang; Yang, Feng; Li, Ran; Gao, Junling; Lin, Yajun

doi:10.3892/ol.2013.1398

Cited by 6 publications

(5 citation statements)

References 21 publications

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“…Our previous studies showed that rhein lysinate (RHL), the salt of rhein and lysine that is easily dissolved in water, inhibited the proliferation of breast (25) and ovarian cancer (26), hepatocellular carcinoma (26), cervical cancer (27,28), and lung carcinoma cells (29), and human umbilical vein endothelial cells (HUVECs) (28). However, the IC 50 was found to be higher in normal cells, meaning that the drug can be used to prevent the proliferation of cancer cells at a lower concentration, without a strong effect on normal cells.…”

Section: Introductionmentioning

confidence: 99%

Antitumor activity of rhein lysinate against human glioma U87 cells in vitro and in vivo

et al. 2015

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In previous studies, we demonstrated that rhein lysinate (RHL), the salt of rhein and lysine that is easily dissolved in water, inhibited the growth of tumor cells derived from breast and ovarian cancer, hepatocellular carcinoma, cervical cancer and lung carcinoma. Based on these observations, human glioma U87 cells and a xenograft model in BALB/c nude mice were used to examine the antitumor activity of RHL against human glioma. Notably, RHL statistically significantly suppressed the growth of human glioma U87 xenografts in BALB/c nude mice. In vitro, there was a significant reduction in cell proliferation after treatment with RHL in a dose- and time-dependent manner. The overall growth inhibition was correlated with the increase in reactive oxygen species (ROS) production and cell apoptosis. The apoptosis- and cell cycle-related proteins including BAX and Bim were increased, whereas Bcl-2 and cyclin D were decreased in the RHL-treated cells. The results demonstrated that RHL is highly effective against the growth of human glioma U87 xenografts in BALB/c nude mice. The potent antitumor activity of RHL may be mediated through downregulation of Bcl-2 and cyclin D expression and upregulation of BAX and Bim expression.

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Section: Introductionmentioning

confidence: 99%

Antitumor activity of rhein lysinate against human glioma U87 cells in vitro and in vivo

et al. 2015

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“…The combination of rhein lysinate and paclitaxel can significantly inhibit H460 and A549 cell proliferation. Rhein lysinate enhances paclitaxel-elicited cytotoxicity via downregulating the activity of ERK and upregulating the expression of cleaved PARP and caspase-3 [60].…”

Section: Quinonoids Enhance the Antilung Cancer Effect Of Othermentioning

confidence: 99%

Quinonoids: Therapeutic Potential for Lung Cancer Treatment

Ying

Chen

et al. 2020

BioMed Research International

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Lung cancer is the leading cause of cancer-related deaths worldwide. Owing to its high incidence and mortality, the development and discovery of novel anticancer drugs is of great importance. In recent years, many breakthroughs have been achieved in the search for effective anticancer substances from natural products. Many anticancer drugs used clinically and proven to be effective are derived from natural products. Quinonoids, including naphthoquinones, phenanthrenequinones, benzoquinones, and anthraquinones, constitute a large group of natural bioactive compounds that widely exist in higher and lower plant species. Given that most of these compounds possess anticancer effects, they are applied in many cancer studies, especially in lung cancer research. They can promote apoptosis, induce autophagy, and inhibit proliferation, angiogenesis, and cell invasion and migration. Some drugs can enhance anticancer effects when combined with other drugs. Thus, quinonoids have broad application prospects in the treatment of lung cancer. Here, we summarize the previous studies on the antilung cancer activities of quinonoids together with their underlying mechanisms and analyze the common research targets with different effects so as to provide references for the discovery of quinonoids against lung cancer.

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“…5 In some other experiments, rhein showed a strong inhibitory effect on the proliferation of many types of cancer cells including HCC cell lines BEL-7402 and HepG2. [6][7][8][9][10][11] Rhein is generally accepted to exert its pharmacological effects primarily via the intrinsic mitochondrial pathway and to interfere with mitochondrial respiratory chain functions, 12 which is considerably different from the DNA-targeted chemotherapy drug DOX. We hypothesized that the combination of rhein and DOX could exert synergistic anticancer effects in human HCC cells.…”

Section: Introductionmentioning

confidence: 99%

“…In previous studies, we have focused on the material foundation and mechanistic action of rhubarb; rhein was found to have the highest probability of being the main active ingredient for the treatment of noxious heat with blood stasis syndrome by the UPLC‐ESI‐Q‐TOF‐MS method . In some other experiments, rhein showed a strong inhibitory effect on the proliferation of many types of cancer cells including HCC cell lines BEL‐7402 and HepG2 . Rhein is generally accepted to exert its pharmacological effects primarily via the intrinsic mitochondrial pathway and to interfere with mitochondrial respiratory chain functions, which is considerably different from the DNA‐targeted chemotherapy drug DOX.…”

Section: Introductionmentioning

confidence: 99%

Synergistic antitumor effects of rhein and doxorubicin in hepatocellular carcinoma cells

Liu

Cao

et al. 2018

J of Cellular Biochemistry

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The aim of this study was to investigate the synergistic antitumor activity of rhein and doxorubicin (DOX) and to elucidate the underlying mechanisms in hepatocellular SMMC‐7721 and HepG2 cells. Cell growth curves, caspase‐3 activity, and intracellular DOX accumulation were observed using an IncuCyte real‐time video imaging system. Combination index was used to calculate synergistic potential of rhein and DOX. Cell apoptosis was detected by the Annexin V‐FITC/PI apoptosis kit. Lactate dehydrogenase and adenosine triphosphate (ATP) levels were assessed using an assay kit. Oxygen consumption rates (OCR) and extracellular acidification rates were assessed by the Seahorse XFe96 Extracellular Flux Analyzer. Mitochondrial inner membrane potential (ΔΨm) was monitored with JC‐1 fluorescence. Western blot analysis was used to detect the level of P‐glycoprotein. Synergistic antiproliferative and proapoptotic effects were exerted by the combination of rhein at 10 μM and DOX at 2 μM in SMMC‐7721 and HepG2 cells. Rhein could influenced the accumulation of DOX in both cells, which was associated with remarkably decreased mitochondrial energy metabolism and ATP levels. Rhein could reduce ΔΨm in both cells. mPTP, opener atractyloside (ATR) could accelerate the loss of ΔΨm, and further suppress the OCR induced by rhein. In contrast, the mPTP blocker cyclosporin A (Cs A) inhibited the loss of ΔΨm and the OCR induced by rhein. Our data indicate that a decline in mitochondrial energy metabolism was responsible for the synergistic antitumor effects of rhein and DOX in hepatocellular carcinoma cells. Reduction of ΔΨm and opening of mPTP inhibited the exchange of ATP/adenosine diphosphate between mitochondrial matrix and cytoplasm is the important mechanism.

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Synergy of Taxol and rhein lysinate associated with the downregulation of ERK activation in lung carcinoma cells

Cited by 6 publications

References 21 publications

Antitumor activity of rhein lysinate against human glioma U87 cells in vitro and in vivo

Antitumor activity of rhein lysinate against human glioma U87 cells in vitro and in vivo

Quinonoids: Therapeutic Potential for Lung Cancer Treatment

Synergistic antitumor effects of rhein and doxorubicin in hepatocellular carcinoma cells

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