Betulinic Acid Induces Bax/Bak-Independent Cytochrome c Release in Human Nasopharyngeal Carcinoma Cells

Liu, Yang; Luo, Wenlong

doi:10.1007/s10059-012-0022-5

Cited by 27 publications

(20 citation statements)

References 39 publications

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“…113 Although these results are contradictory, they suggest that the role of Bcl-2 family members in the apoptosis induced by anticancer agents is complex and based on these above findings, it was concluded that presence of BA leads to mitochondrial apoptosis probably through direct opening of the permeability transition (PT) pore. Similar results have been found by Liu et al 114 Such an effect can be temporarily abrogated by antiapoptotic Bcl-2 family members. 113 It was also found that p53 wild-type and p53 mutant RMS cells are sensitive to BA treatment, assuming that the p53 pathway fails to take part in the regulation of BA-induced apoptosis in RMS cells.…”

Section: Induction Of Apoptosissupporting

confidence: 90%

Betulinic Acid and its Derivatives as Potential Antitumor Agents

Zhang

Wang

et al. 2015

Medicinal Research Reviews

160

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Betulinic acid (BA) is a lupane-type pentacyclic triterpene, distributed ubiquitously throughout the plant kingdom. BA and its derivatives demonstrate multiple bioactivities, particularly an antitumor effect. This review critically describes the recent research on isolation, synthesis, and derivatization of BA and its natural analogs betulin and 23-hydroxybetulinic acid. The subsequent part of the review focuses on the current knowledge of antitumor properties, combination treatments, and pharmacological mechanisms of these compounds. A 3D-QSAR analysis of 62 BA derivatives against human ovarian cancer A2780 is also included to provide information concerning the structure-cytotoxicity relationships of these compounds.

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Section: Induction Of Apoptosissupporting

confidence: 90%

Betulinic Acid and its Derivatives as Potential Antitumor Agents

Zhang

Wang

et al. 2015

Medicinal Research Reviews

160

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“…In mitochondria mediated apoptotic cell death process Bax acts as an essential gatekeeper as its activation irreversibly commits the most of the cells to die [40,41]. It has been studied extensively on its relationship with different types of cancer, such as pancreatic [19,42], bladder [21], gastric [18], colorectal [43,44], esophageal [16], lung [32,45,46], cervical [47], colon [48,49], prostate carcinoma [50,51], squamous cell carcinoma of the head and neck [36], nasopharyngeal carcinoma [52], breast carcinomas [32,53], ovarian carcinoma [54], renal and transitional cell cancer [55], gliomas [56], CLL [30,31,33–35,38,57], Hodgkin’s lymphoma [17], non-Hodgkin's lymphoma [58], myeloma [59], acute leukemia [60], etc. Bax promoter contains response elements for an important tumor suppressor p53 and this affects gene expression [28].…”

Section: Discussionmentioning

confidence: 99%

Lack of Association between Bax Promoter (-248G>A) Single Nucleotide Polymorphism and Susceptibility towards Cancer: Evidence from a Meta-Analysis

Sahu

Choudhuri

2013

PLoS ONE

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BackgroundThe Bcl-2-associated X protein (Bax) is a proapoptotic member of the Bcl-2 family known to be activated and upregulated during apoptosis. Single nucleotide polymorphisms (SNPs) in Bax promoter may participate in the process of carcinogenesis by altering its own expression and the cancer related genes. Bax-248G>A polymorphism has been implicated to alter the risk of cancer, but the listed results are inconsistent and inconclusive. In the present study, we performed a meta-analysis to systematically summarize the possible association of this polymorphism with the risk of cancer.MethodologyWe conducted a search of case-control studies on the associations of Bax-248G>A polymorphism with susceptibility to cancer in Pub Med, Science Direct, Wiley Online Library and hand search. Data from all eligible studies based on some key search terms, inclusion and exclusion criteria were extracted for this meta-analysis. Hardy-Weinberg equilibrium (HWE) in controls, power calculation, heterogeneity analysis, Begg’s funnel plot, Egger’s linear regression test, forest plot and sensitivity analysis were performed in the present study.ResultsCancer risk associated with Bax-248G>A polymorphism was estimated by pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). The pooled ORs were calculated in allele contrast, homozygous comparison, heterozygous comparison, dominant and recessive model. Statistical significance was checked through Z and p-value in forest plot. A total of seven independent studies including 1772 cases and 1708 controls were included in our meta-analysis. Our results showed that neither allele frequency nor genotype distributions of this polymorphism were associated with risk for cancer in any of the genetic model. Furthermore, Egger’s test did not show any substantial evidence of publication bias.Conclusions/SignificanceThis meta-analysis suggests that the Bax-248G>A polymorphism is not an important cancer risk factor. Nevertheless, additional well-designed studies with larger sample size focusing on different ethnicities and cancer types are required to further validate the results.

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“…Apoptosis is a programmed cell death consisting in morphological changes including cell shrinkage, nuclear condensation, chromosomal DNA fragmentation, plasma membrane blebbing and caspase activation [121]. In this regard, apoptosis is considered a crucial physiological process in tumor clearance, being a major target for anticancer drugs [122]. The molecular mechanisms of apoptosis can include extrinsic and intrinsic pathways.…”

Section: Pentacyclic Triterpenes: Mechanism Of Action At Cellular Andmentioning

confidence: 99%

Lupan-Skeleton Pentacyclic Triterpenes with Activity against Skin Cancer: Preclinical Trials Evolution

Şoica¹,

Antal²,

Andrica³

et al. 2017

Unique Aspects of Anti-Cancer Drug Development

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Skin cancer is an increasingly frequent pathology, with a dangerous high percentage of malignant melanoma. The use of synthetic chemotherapy raises the problem of severe adverse effects and the development of resistance to treatment. Therefore, the use of natural therapies became the focus of numerous research groups due to their high efficacy and lower systemic adverse effects. Among natural products evaluated as therapeutical agents against skin cancer, betulinic acid was emphasized as a highly selective anti-melanoma agent and is currently undergoing phase II clinical trials as topical application. Several other pentacyclic triterpenes exhibit antiproliferative activities. This chapter aims to present the latest main discoveries in the class of pentacyclic triterenes with antitumor effect and the evolution of their preclinical trials. Furthermore, it includes reports on plant sources containing pentacyclic triterpenes, as well as the main possibilities of their water solubilization and cancer cell targeting. A review on recent data regarding mechanisms of action at cellular and molecular levels complements information on the outstanding medicinal potential of these compounds.

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Betulinic Acid Induces Bax/Bak-Independent Cytochrome c Release in Human Nasopharyngeal Carcinoma Cells

Cited by 27 publications

References 39 publications

Betulinic Acid and its Derivatives as Potential Antitumor Agents

Betulinic Acid and its Derivatives as Potential Antitumor Agents

Lack of Association between Bax Promoter (-248G>A) Single Nucleotide Polymorphism and Susceptibility towards Cancer: Evidence from a Meta-Analysis

Lupan-Skeleton Pentacyclic Triterpenes with Activity against Skin Cancer: Preclinical Trials Evolution

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