Chinese Medicines Induce Cell Death: The Molecular and Cellular Mechanisms for Cancer Therapy

Wang, Xuanbin; Feng, Yibin; Wang, Ning; Cheung, Fanny M.; Tan, Hor Yue; Zhong, Sen; Li, Charlie; Kobayashi, Seiichi

doi:10.1155/2014/530342

Cited by 37 publications

(42 citation statements)

References 154 publications

(91 reference statements)

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“…The success with natural product shikonin, which able to induce multiple cell death mechanisms, supports the notion that natural compounds could bypass specific drug resistance developed by tumor cells using simultaneous activation of multiple death pathways (apoptosis, autophagy, necroptosis), as reviewed elsewhere [20, 29, 42, 45, 65, 96, 108, 111, 158, 337-343]. Thus, a rationalized combination of several cell death inducers that complement each other would maximize their efficacy while minimizing their side effects [20, 29, 42, 45, 65, 96, 108, 111, 158, 337-343]. While in vitro studies showed the strong ability of natural compounds to induce non-apoptotic death of tumor cells, more in vivo investigations needed to strengthen this notion before making a leap to clinical application [339-343].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 57%

Natural Compounds As Modulators of Non-apoptotic Cell Death in Cancer Cells

Guamán-Ortiz

Orellana²,

Ratovitski³

2017

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Cell death is an innate capability of cells to be removed from microenvironment, if and when they are damaged by multiple stresses. Cell death is often regulated by multiple molecular pathways and mechanism, including apoptosis, autophagy, and necroptosis. The molecular network underlying these processes is often intertwined and one pathway can dynamically shift to another one acquiring certain protein components, in particular upon treatment with various drugs. The strategy to treat human cancer ultimately relies on the ability of anticancer therapeutics to induce tumor-specific cell death, while leaving normal adjacent cells undamaged. However, tumor cells often develop the resistance to the drug-induced cell death, thus representing a great challenge for the anticancer approaches. Numerous compounds originated from the natural sources and biopharmaceutical industries are applied today in clinics showing advantageous results. However, some exhibit serious toxic side effects. Thus, novel effective therapeutic approaches in treating cancers are continued to be developed. Natural compounds with anticancer activity have gained a great interest among researchers and clinicians alike since they have shown more favorable safety and efficacy then the synthetic marketed drugs. Numerous studies in vitro and in vivo have found that several natural compounds display promising anticancer potentials. This review underlines certain information regarding the role of natural compounds from plants, microorganisms and sea life forms, which are able to induce non-apoptotic cell death in tumor cells, namely autophagy and necroptosis.

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Section: Conclusion and Future Perspectivesmentioning

confidence: 57%

Natural Compounds As Modulators of Non-apoptotic Cell Death in Cancer Cells

Guamán-Ortiz

Orellana²,

Ratovitski³

2017

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“…Biomedical research and cancer treatment clinical trials have provided evidence regarding the use of herbal medicines; therefore, they are increasingly being accepted as a complementary and alternative treatment (1). In addition, natural medicines have been reported to have an important role in human health, particularly certain well-studied plants, including Taxus chinensis (Taxus madia) (2), Radix Sophorae flavescentis (Sophora flavescens) (3), Alkanna tinctoria, Lithospermum erythrorhizon and licorice (Glycyrrhiza L) (4).…”

Section: Introductionmentioning

confidence: 99%

Licochalcone A induces T24 bladder cancer cell apoptosis by increasing intracellular calcium levels

Yang

Jiang

Yang

et al. 2016

Molecular Medicine Reports

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Abstract. Licochalcone A (LCA) has been reported to significantly inhibit cell proliferation, increase reactive oxygen species (ROS) levels, and induce apoptosis of T24 human bladder cancer cells via mitochondria and endoplasmic reticulum (ER) stress-triggered signaling pathways. Based on these findings, the present study aimed to investigate the mechanisms by which LCA induces apoptosis of T24 cells. Cultured T24 cells were treated with LCA, and cell viability was measured using the sulforhodamine B assay. Apoptosis was detected by flow cytometry with Annexin V/propidium iodide staining, and by fluorescent microscopy with Hoechst 33258 staining. The levels of intracellular free calcium ions were determined using Fluo-3 AM dye marker. Intracellular ROS levels were assessed using the 2' ,7'-dichlorodihydrofluorescein diacetate probe assay. The mitochondrial membrane potential was measured using 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl benzimidazole carbocyanine iodide. Furthermore, the mRNA expression levels of B-cell lymphoma (Bcl)-extra large, Bcl-2-associated X protein, Bcl-2-interacting mediator of cell death, apoptotic protease activating factor-1 (Apaf-1), calpain 2, cysteinyl aspartate specific proteinase (caspase)-3, caspase-4 and caspase-9 were determined using reverse transcription semiquantitative and quantitative polymerase chain reaction analyses. Treatment with LCA inhibited proliferation and induced apoptosis of T24 cells, and increased intracellular Ca 2+ levels and ROS production. Furthermore, LCA induced mitochondrial dysfunction, decreased mitochondrial membrane potential, and increased the mRNA expression levels of Apaf-1, caspase-9 and caspase-3. Exposure of T24 cells to LCA also triggered calpain 2 and caspase-4 activation, resulting in apoptosis. These findings indicated that LCA increased intracellular Ca 2+ levels, which may be associated with mitochondrial dysfunction. In addition, the ER stress pathway may be considered an important mechanism by which LCA induces apoptosis of T24 bladder cancer cells. IntroductionNatural herbal medicines have long been used to treat cancer. Biomedical research and cancer treatment clinical trials have provided evidence regarding the use of herbal medicines; therefore, they are increasingly being accepted as a complementary and alternative treatment (1). In addition, natural medicines have been reported to have an important role in human health, particularly certain well-studied plants, including Taxus chinensis (Taxus madia) (2), Radix Sophorae flavescentis (Sophora flavescens) (3), Alkanna tinctoria, Lithospermum erythrorhizon and licorice (Glycyrrhiza L) (4). Licorice is one of the most commonly prescribed herbs in Chinese Traditional Medicine, and has been used for >2,000 years. The effects of licorice have been reported on various diseases, ranging from microbial infection to cancer (5-7). However, since herbs usually contain numerous chemical compositions, the mechanism of action of these herbs is currently unclear. Recently, several chemical ing...

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“…The inhibition of proliferation and promotion of apoptosis remain the standard approach of anticancer therapy. For improved therapeutic effect and higher quality of life, multi-target therapy should be emphasized, and the majority of TCMs including HDW exhibit advantages in this respect (27,28). HDW has been reported to be clinically effective with few side effects (5).…”

Section: Discussionmentioning

confidence: 99%

Chloroform extract of Hedyotis diffusa Willd inhibits viability of human colorectal cancer cells via suppression of AKT and ERK signaling pathways

et al. 2017

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Abstract.Hedyotis diffusa Willd (HDW) is a widely used traditional Chinese medicine in clinical therapy to treat various types of cancer, including colorectal cancer (CRC), but its effective polar fractions and functional mechanisms remain unclear. The aim of the present study was to determine the most effective extract of HDW and to investigate its effects on the regulation of CRC cell proliferation and apoptosis, as well as to investigate the underlying molecular mechanisms. The results demonstrated that the chloroform extract of HDW (CEHDW) exhibited the most anticancer ability. Furthermore, results of the MTT assay, colony formation, carboxyfluorescein diacetate succinimidyl ester assay and annexin V/propidium iodide staining suggested that CEHDW significantly inhibits proliferation and promotes apoptosis in the SW620 CRC cell line. Additionally, reverse transcription-polymerase chain reaction and western blot analysis demonstrated that CEHDW treatment downregulated the expression of Survivin, proliferating cell nuclear antigen, Cyclin D1, cyclin-dependent kinase 4 and B-cell lymphoma 2 (Bcl-2), and upregulated the expression of Bcl-2-associated X protein at the mRNA and protein levels. CEHDW also decreased the phosphorylation of protein kinase B (AKT) and extracellular-signal-regulated kinase (ERK), which indicated that the suppression of the AKT and ERK signaling pathways may be one of the underlying molecular mechanisms by which CEHDW exhibited its anticancer effect. Thus, CEHDW may be a promising agent for anticancer therapy.

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Chinese Medicines Induce Cell Death: The Molecular and Cellular Mechanisms for Cancer Therapy

Cited by 37 publications

References 154 publications

Natural Compounds As Modulators of Non-apoptotic Cell Death in Cancer Cells

Natural Compounds As Modulators of Non-apoptotic Cell Death in Cancer Cells

Licochalcone A induces T24 bladder cancer cell apoptosis by increasing intracellular calcium levels

Chloroform extract of Hedyotis diffusa Willd inhibits viability of human colorectal cancer cells via suppression of AKT and ERK signaling pathways

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