Betulinic Acid as a Potent and Complex Antitumor Phytochemical: A Minireview

Gheorgheosu, Dorina; Duicu, Oana; Dehelean, Cristina; Şoica, Codruţa; Muntean, Daniela-Lucia

doi:10.2174/1871520614666140223192148

Cited by 76 publications

(55 citation statements)

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“…A tripchlorolide was shown to suppress the tumor cell growth and induce autophagic cell death in human lung cancer A549 cells, as well as in human neuroblastoma SH-SY5Y cells with no observed signs of apoptosis [179, 182, 183]. Betulinic acid is a triterpenoid isolated from the bark of the white birch tree, exhibited anticancer properties against several tumor cells in vitro and in vivo [184, 185]. Betulinic acid and its analogues were found to decrease the phosphorylation of AKT and induce autophagic cell death in human glioblastoma cells, as described in [186].…”

Section: Anticancer Natural Compounds and Autophagymentioning

confidence: 99%

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: Anticancer Natural Compounds and Autophagymentioning

confidence: 99%

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

Guamán-Ortiz

Orellana²,

Ratovitski³

2017

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“…& Zeyh.) Kuntze [21] Roscovitine Antitumor, anticancer agent Raphanus sativus L. Plant-derived anticancer agents in preclinical development [22] Betulinic acid Anticancerous Betula alba Indian jujube-Ziziphus mauritiana Anemone -Anemone raddeana Club mosses-Lycopodium cernuum Trumpet satinash-Syzygium claviflorum [23] Bruceantin Anticancerous Brucea antidysenterica [24] Pervilleine A Anticancerous Erythroxylum pervillei Baillon [25] b-Lapachone Anticancerous Tabebuia serratifolia [26] 2-Cyano-3, 12-dioxoolean-1, 9-dien-28-oic acid (CDDO)…”

Section: Isolation Purification and Synthesismentioning

confidence: 99%

Betulinic Acid: Recent Advances in Chemical Modifications, Effective Delivery, and Molecular Mechanisms of a Promising Anticancer Therapy

et al. 2015

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An important method of drug discovery is examination of diverse life forms, including medicinal plants and natural products or bioactive compounds isolated from these sources. In cancer research, lead structures of compounds from natural sources can be used to design novel chemotherapies with enhanced biological properties. Betulinic acid (3β-hydroxy-lup-20(29)-en-28-oic acid or BetA) is a naturally occurring pentacyclic triterpene with a wide variety of biological activities, including potent antitumor properties. Non-malignant cells and normal tissues are not affected by BetA. Because BetA exerts its effects directly on the mitochondrion and triggers death of cancerous cells, it is an important alternative when certain chemotherapy drugs fail. Mitochondrion-targeted agents such as BetA hold great promise to circumvent drug resistance in human cancers. BetA is being developed by a large network of clinical trial groups with the support of the U.S. National Cancer Institute. This article discusses recent advances in research into anticancer activity of BetA, relevant modes of delivery, and the agent's therapeutic efficacy, mechanism of action, and future perspective as a pipeline anticancer drug. BetA is a potentially important agent in cancer therapeutics.

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“…In the last decades, the biological activities and medicinal properties of BA have been intensively investigated; the results revealed that BA exhibits a plethora of beneficial properties, including anti‐tumour, anti‐angiogenic, anti‐inflammatory, anti‐fibrotic, anti‐HIV, and hepatoprotective effect . Furthermore, the most concerned activity of BA is anti‐tumoral activity currently, it has reported that BA shows significant cytotoxic on various tumour cell lines originating from lung, colon, prostate, and ovary, and in animal models in vivo . However, only a few papers on liver cancer were published.…”

Section: Introductionmentioning

confidence: 99%

Betulinic acid induces apoptosis and suppresses metastasis in hepatocellular carcinoma cell lines in vitro and in vivo

Wang¹,

Wang

Liu

et al. 2018

J Cellular Molecular Medi

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Hepatocellular carcinoma (HCC) is a high incidence and mortality malignant tumour globally. Betulinic acid (BA) is a pentacyclic triterpenoid with potential pro‐apoptotic activities which widely found in many plants. In this study, we determined the effects of BA on proliferation, apoptosis, invasion, and metastasis in HCC cell lines and on tumour growth and pulmonary metastasis in mice. The results suggested that BA could inhibit cell viability and proliferation of HCC cell lines including HepG2, LM3, and MHCC97H. In addition, BA induced apoptosis of HepG2 cells characterised condensed nuclei and nuclear fragmentation. Moreover, western blot analysis showed that BA‐induced apoptosis associated with increasing of pro‐apoptotic protein Bax and cleaved caspase‐3 and decreasing of anti‐apoptotic protein Bcl‐2. Meanwhile, BA also reduced the reactive oxygen species (ROS) level. Furthermore, BA also significantly inhibited HCC growth in vivo and blocked pulmonary metastasis of HCC by regulating the metastasis‐related proteins including MMP‐2, MMP‐9, and TIMP2 without obvious toxicity. In all, the present study suggested that BA might be a promising anti‐HCC drug candidate by inhibiting proliferation, inducing apoptosis, and blocking metastasis.

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Betulinic Acid as a Potent and Complex Antitumor Phytochemical: A Minireview

Cited by 76 publications

References 0 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

Betulinic Acid: Recent Advances in Chemical Modifications, Effective Delivery, and Molecular Mechanisms of a Promising Anticancer Therapy

Betulinic acid induces apoptosis and suppresses metastasis in hepatocellular carcinoma cell lines in vitro and in vivo

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