PDF(Sci-hub)
Abstract：
BACKGROUND: D-limonene and its derivatives have demonstrated potential chemopreventive and anticancer activity in preclinical and clinical studies. The aim of this scoping review was to assess and critically appraise current literature on the effect of these bioactive citrus peel compounds on breast cancer in human trials and to identify knowledge gaps for exploration in future studies.
METHODS: This study followed a scoping review framework. Peer-reviewed journal articles were included if they reported the effect of d-limonene or its derivatives on breast cancer in human subjects. Articles were retrieved from academic databases - PubMed, EMBASE, CINAHL, Web of Science, and Cochrane reviews - and iteratively through review of bibliographies of relevant manuscripts. Titles and abstracts were appraised against the aforementioned inclusion criteria in a first round of screening. Through consensus meetings and full article review by authors, a final set of studies were selected. Results were reported according to the PRISMA extension for scoping reviews.
RESULTS: Our search strategy yielded 367 records. Following screening and adjudication, five articles reporting on phase 1(n = 2), phase 2 (n = 2) and both trial phases (n = 1) were included as the final dataset for this review. Trials evaluating the effect of d-limonene (n = 2) showed it was well tolerated in subjects. One study (n = 43 participants) showed d-limonene concentrated in breast tissue (mean 41.3 μg/g tissue) and reduction in tumor cyclin D1 expression, which is associated with tumor proliferation arrest. This study did not show meaningful change in serum biomarkers associated with breast cancer, except for a statistically significant increase in insulin-like growth factor-1 (IGF-I) levels. While elevation of IGF-I is associated with increased cancer risk, the clinical implication of this study remains uncertain given its short duration. Trials with perillyl alcohol (n = 3) showed low tolerance and no effect on breast cancer.
CONCLUSIONS: This review demonstrated a dearth of clinical studies exploring the effect of d-limonene and its derivatives on breast cancer. Limited literature suggests d-limonene is safe and tolerable in human subjects compared to its derivative, perillyl alcohol. Our review demonstrates the need for additional well-powered placebo-controlled trials that assess d-limonene\'s efficacy on breast cancer compared to other therapies.
METHODS: This study followed a scoping review framework. Peer-reviewed journal articles were included if they reported the effect of d-limonene or its derivatives on breast cancer in human subjects. Articles were retrieved from academic databases - PubMed, EMBASE, CINAHL, Web of Science, and Cochrane reviews - and iteratively through review of bibliographies of relevant manuscripts. Titles and abstracts were appraised against the aforementioned inclusion criteria in a first round of screening. Through consensus meetings and full article review by authors, a final set of studies were selected. Results were reported according to the PRISMA extension for scoping reviews.
RESULTS: Our search strategy yielded 367 records. Following screening and adjudication, five articles reporting on phase 1(n = 2), phase 2 (n = 2) and both trial phases (n = 1) were included as the final dataset for this review. Trials evaluating the effect of d-limonene (n = 2) showed it was well tolerated in subjects. One study (n = 43 participants) showed d-limonene concentrated in breast tissue (mean 41.3 μg/g tissue) and reduction in tumor cyclin D1 expression, which is associated with tumor proliferation arrest. This study did not show meaningful change in serum biomarkers associated with breast cancer, except for a statistically significant increase in insulin-like growth factor-1 (IGF-I) levels. While elevation of IGF-I is associated with increased cancer risk, the clinical implication of this study remains uncertain given its short duration. Trials with perillyl alcohol (n = 3) showed low tolerance and no effect on breast cancer.
CONCLUSIONS: This review demonstrated a dearth of clinical studies exploring the effect of d-limonene and its derivatives on breast cancer. Limited literature suggests d-limonene is safe and tolerable in human subjects compared to its derivative, perillyl alcohol. Our review demonstrates the need for additional well-powered placebo-controlled trials that assess d-limonene\'s efficacy on breast cancer compared to other therapies.
摘要：
背景：D-柠檬烯及其衍生物在临床前和临床研究中已显示出潜在的化学预防和抗癌活性。本范围审查的目的是评估和批判性地评估当前文献中有关这些生物活性柑橘皮化合物对人体试验中乳腺癌的影响，并确定知识空白，以供将来的研究探索。
方法：本研究遵循范围审查框架。如果同行评审的期刊文章报道了d-柠檬烯或其衍生物对人类受试者乳腺癌的影响，则包括在内。文章从学术数据库中检索-PubMed，EMBASE,CINAHL,WebofScience,和Cochrane评论-并反复审查相关手稿的参考书目。在第一轮筛选中，对照上述纳入标准对标题和摘要进行了评估。通过共识会议和作者的全文审查，我们选择了最后一组研究.根据PRISMA扩展范围审查报告结果。
结果：我们的搜索策略产生了367条记录。经过筛选和裁决，五篇报告第一阶段的文章(n=2)，2期(n=2)和两个试验阶段(n=1)作为本综述的最终数据集.评价d-柠檬烯(n=2)的作用的试验显示其在受试者中具有良好的耐受性。一项研究（n=43名参与者）显示d-柠檬烯集中在乳腺组织（平均41.3μg/g组织）和肿瘤细胞周期蛋白D1表达减少，这与肿瘤增殖停滞有关。这项研究没有显示与乳腺癌相关的血清生物标志物有意义的变化，除了胰岛素样生长因子-1（IGF-I）水平的统计学显着增加。虽然IGF-I的升高与癌症风险增加有关，由于研究持续时间短,本研究的临床意义仍不确定.紫苏醇（n=3）的试验显示耐受性低，对乳腺癌没有影响。
结论：这篇综述表明缺乏探索d-柠檬烯及其衍生物对乳腺癌影响的临床研究。有限的文献表明d-柠檬烯与其衍生物相比在人类受试者中是安全和可耐受的。紫苏醇。我们的综述表明，与其他疗法相比，需要更多有效的安慰剂对照试验来评估d-柠檬烯对乳腺癌的疗效。
方法：本研究遵循范围审查框架。如果同行评审的期刊文章报道了d-柠檬烯或其衍生物对人类受试者乳腺癌的影响，则包括在内。文章从学术数据库中检索-PubMed，EMBASE,CINAHL,WebofScience,和Cochrane评论-并反复审查相关手稿的参考书目。在第一轮筛选中，对照上述纳入标准对标题和摘要进行了评估。通过共识会议和作者的全文审查，我们选择了最后一组研究.根据PRISMA扩展范围审查报告结果。
结果：我们的搜索策略产生了367条记录。经过筛选和裁决，五篇报告第一阶段的文章(n=2)，2期(n=2)和两个试验阶段(n=1)作为本综述的最终数据集.评价d-柠檬烯(n=2)的作用的试验显示其在受试者中具有良好的耐受性。一项研究（n=43名参与者）显示d-柠檬烯集中在乳腺组织（平均41.3μg/g组织）和肿瘤细胞周期蛋白D1表达减少，这与肿瘤增殖停滞有关。这项研究没有显示与乳腺癌相关的血清生物标志物有意义的变化，除了胰岛素样生长因子-1（IGF-I）水平的统计学显着增加。虽然IGF-I的升高与癌症风险增加有关，由于研究持续时间短,本研究的临床意义仍不确定.紫苏醇（n=3）的试验显示耐受性低，对乳腺癌没有影响。
结论：这篇综述表明缺乏探索d-柠檬烯及其衍生物对乳腺癌影响的临床研究。有限的文献表明d-柠檬烯与其衍生物相比在人类受试者中是安全和可耐受的。紫苏醇。我们的综述表明，与其他疗法相比，需要更多有效的安慰剂对照试验来评估d-柠檬烯对乳腺癌的疗效。
