Anti-cancer properties of terpenoids isolated from Rhizoma Curcumae – A review

Lu, Jin‐Jian; Dang, Yanan; Huang, Min; Xu, Wen-Shan; Chen, Xiuping; Wang, Ying

doi:10.1016/j.jep.2012.07.009

Cited by 159 publications

(94 citation statements)

References 52 publications

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“…Data obtained from flow cytometry and cellular morphology studies demonstrate that curcumol is capable of inhibiting the growth of TNBC MDA-MB 231 cells in a predominantly apoptotic manner. These results are consistent with those observed in various other tumor cell lines (14)(15)(16)(17). Furthermore, the present study supported the evidence indicating a marked effect of curcumol in a BALB/c nude mice xenograft model.…”

Section: Discussionsupporting

confidence: 93%

“…China (11). Curcumol is one of the major pharmacological components of the aforementioned essential oil, and has recently been reported to exhibit an anti-proliferative effect on numerous human tumor cell lines, including lung, breast, ovary, liver, gastric and intestinal cancer (14)(15)(16)(17). To the best of our knowledge, the present study is the first to provide evidence of the anticancer effect of curcumol in a p53 mutant TNBC MDA-MB-231 cell line, via demonstrating a direct inhibition of cellular viability and xenograft growth, and the induction of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…A total of six volatile compounds (curdione, curcumol, germacrone, curzerene, 1,8-cineole and β-elemene) have been successfully isolated from the essential oil of Curcuma wenyujin (12). As one of the major components of the essential oil, curcumol, Curcumol triggers apoptosis of p53 mutant triple-negative human breast cancer MDA-MB 231 cells via activation of p73 and PUMA C 15 H 24 O 2-(3s-(3a, 3aa,5a,6a,8ab))-octahydro-3-methyl-8-methylene-5-(1-methylethyl)-6h-3a, 6-epoxyazulen-6-ol (13), has been reported to be capable of blocking the proliferation of various types of human tumor cells, including lung, prostate and ovarian cancer cell lines in vitro and inducing apoptosis via a caspase-independent mitochondrial pathway in ASTC-a-1 cells (14)(15)(16)(17). However, the molecular mechanisms underlying curcumol-induced anti-proliferative effects are still unknown.…”

Section: Curcuma Wenyujin Y H Chen Et C Ling (Curcuma Wenyujin)mentioning

confidence: 99%

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Curcumol triggers apoptosis of p53 mutant triple-negative human breast cancer MDA-MB 231 cells via activation of p73 and PUMA

Huang

Liao

et al. 2017

Oncology Letters

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Abstract. Triple-negative breast cancer (TNBC; estrogen receptor-negative, progesterone receptor-negative and Her-2-negative) is often accompanied by a higher frequency of p53 gene mutations. Therefore, TNBC is challenging to treat due to a lack of biological targets and a poor sensitivity to conventional therapies. Curcumol is a monomer composition isolated from the ethanol extracts of Curcuma wenyujin, a Chinese medicinal herb traditionally used as a cancer remedy. Previous studies have revealed that curcumol is able to block proliferation in various human tumor cell lines. However, the underlying mechanisms have yet to be elucidated. The present study aimed to investigate the anticancer effects of curcumol in the human p53 mutant TNBC MDA-MB-231 cell line and its underlying mechanisms. Cell viability and growth were determined by MTT and a mice xenograft model assay, respectively. Cell cycle distribution was examined by flow cytometry. Apoptosis was evaluated by apoptotic morphology analysis with DAPI staining and flow cytometric analysis following Annexin V/propidium iodide staining. The protein expression in cells was eva luated by immunoblotting. Treatment of MDA-MB-231 cells with curcumol resulted in a significant inhibition of cell proliferation in vitro [half maximal inhibitory concentration (IC 50 )=240.7±85.0 µg/ml for 48 h and IC 50 =100.2±13.5 µg/ml for 72 h]. Curcumol treatment also resulted in the suppression of xenograft growth in vivo (100 or 200 µg/kg for 21 days), as well as G 1 phase arrest and an apoptotic response, which were accompanied by the upregulation of p73 expression and the activation of the expression of p53 upregulated modulator of apoptosis (PUMA) and Bcl-2 antagonistic killer (Bak). No cleavage of poly (ADP-ribose) polymerase was detected. To the best of our knowledge, the present data demonstrate for the first time that curcumol inhibits the growth of MDA-MB-231 cells and triggers p53-independent apoptosis, which may be media ted by the p73-PUMA/Bak signaling pathway. Curcumol may, therefore, be a potential compound for use in the development of novel TNBC therapeutics. IntroductionTriple-negative breast cancer (TNBC; estrogen receptor-negative, progesterone receptor-negative and Her-2-negative) remains challenging to treat due to the innate aggressive biological characteristics and the lack of effective therapies (1,2). TNBCs represent ~15% of all breast cancer cases and are often accompanied by a higher frequency of p53 gene mutations (2,3). The tumor suppressor gene p53 serves a critical role in conferring cancer cell sensitivity to DNA-damaging agents (3). Failure of p53 signaling leads to resistance to chemotherapeutics (3-5). p73 is a member of the p53 gene family. Under certain conditions, p73 is able to replace the p53 function in response to DNA damage, activate the transcription of p53-responsive genes and inhibit cell growth in a p53-like manner by inducing cell cycle arrest and apoptosis (6-8). Therefore, the identification of anticancer drugs able to activate p73 ...

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Curcuma Wenyujin Y H Chen Et C Ling (Curcuma Wenyujin)mentioning

confidence: 99%

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Curcumol triggers apoptosis of p53 mutant triple-negative human breast cancer MDA-MB 231 cells via activation of p73 and PUMA

Huang

Liao

et al. 2017

Oncology Letters

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“…A number of studies have investigated the clinical application of TCMs for HCC (13,14), demonstrating that β-elemene, which is present in Rhizoma Curcumae and the main component of cidan, may inhibit the proliferation of HepG2 cells in a time-and dose-dependent manner. The results indicated that β-elemene exhibited positive effects on apoptosis and induced the cell cycle arrest of HepG2 cells in the G2/M phase, while Fas and Fas ligand expression levels were markedly increased (15,16). In addition, a meta-analysis demonstrated that β-elemene improved the effect of lung cancer chemotherapy as an adjunctive treatment (14).…”

Section: Introductionmentioning

confidence: 97%

Cidan inhibits liver cancer cell growth by reducing COX-2 and VEGF expression and cell cycle arrest

Zheng

Xue

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Cidan is a traditional Chinese medicine formula that has been used for >10 years as an antitumor drug. In the present study, the antitumor effect of cidan on hepatocellular carcinoma (HCC) and the underlying molecular mechanisms were investigated. A total of 372 patients with primary HCC, as confirmed by pathological examination in the Eastern Hepatobiliary Surgery Hospital and Beijing Oncology Hospital of Weida TCM, were prospectively enrolled in the study. In total, 92 patients were treated with cidan capsules for three months postoperatively, while 280 patients served as controls. The efficacy of cidan was analyzed by monitoring associated symptoms and liver function tests, including measuring the levels of α-1-fetoprotein, α-L-fucosidase, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase and γ-glutamyl transferase. In addition, in vivo analysis was performed using mice Hepa1-6 xenograft models, while in vitro studies were performed with SMMC-7721 and CSQT-1 cells; this included cidan-dependent cell viability and migration assays, cell cycle analyses and the evaluation of cidan effects on cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) mRNA transcription rates using quantitative polymerase chain reaction. The postoperative two-year overall survival (77 and 58% for the cidan and control groups, respectively; P<0.01) and disease-free survival (36 and 24% for the cidan and control groups, respectively; P<0.01) rates were superior in the cidan-treated group when compared with the control. In addition, the size and weight of the tumor xenografts in the C57BL/6 mice were significantly reduced in a time-and dose-dependent manner following cidan treatment (P<0.01). Cidan significantly reduced the cell viability of SMMC-7721 and CSQT-1 cells after four and five days when compared with the control (P<0.01). Furthermore, COX-2 and VEGF mRNA expression levels decreased following cidan treatment (P<0.01), and cidan treatment resulted in enhanced G1 and G2/M cell cycle arrest of CSQT-1 cells. Therefore, cidan effectively inhibited cell proliferation, reduced cell viability and downregulated COX-2 and VEGF expression levels in hepatoma cells.

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“…For example, caryophyllene (detected in this research) is reported to be an agonist to the CB 2 receptor and to provide anti-inflammatory effects [57]. b-Elemene (also detected) has been shown to have anti-carcinogenic properties [58]. In contrast to the potential therapeutic applications of terpenoids, there is also evidence that they are precursors for polyaromatic hydrocarbons [59], which raises the question of toxic side-effects.…”

mentioning

confidence: 74%

Chemical and physical variations of cannabis smoke from a variety of cannabis samples in New Zealand

Sheehan

Hamnett

Beasley

et al. 2018

Forensic Sciences Research

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Studies have compared the chemical properties of tobacco smoke to those of cannabis smoke, with the objective of identifying the chemical attributes responsible for the mutagenicity and carcinogenicity of cannabis smoke. Comparative studies have included small sample sizes and produced conflicting results. The aim of this study was to assess the major chemical and physical variations of cannabis smoke across a range of cannabis samples of different potencies and origins, sourced from the illegal market in New Zealand. Twelve cannabis samples were studied ranging from 1.0% to 13.4% delta-9-tetrahydrocannabinol (D 9 THC) content. A smoking machine was used to smoke "joints" (cannabis cigarettes) and the chemical/physical properties of the smoke assessed. The chemical constituents of the smoke extracts were analysed by gas chromatography/mass spectrometry. A range of different chemical constituents (in addition to D 9 THC) were identified and their concentrations estimated. Terpenoids were identified as the major variable in cannabis smoke, showing a 40-fold range in total terpenoid content. Analysis of the total particulate matter showed that significantly different levels of particulate matter were produced between the different cannabis samples, ranging from 14.6 to 66.3 mg/g of cannabis smoked. The D 9 THC delivery efficiency during smoking was also investigated and produced consistent results showing a mean and median of 12.6% and 10.8%, respectively, of the theoretically available D 9 THC (ranging from 7.2% to 28.0%).

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Anti-cancer properties of terpenoids isolated from Rhizoma Curcumae – A review

Cited by 159 publications

References 52 publications

Curcumol triggers apoptosis of p53 mutant triple-negative human breast cancer MDA-MB 231 cells via activation of p73 and PUMA

Curcumol triggers apoptosis of p53 mutant triple-negative human breast cancer MDA-MB 231 cells via activation of p73 and PUMA

Cidan inhibits liver cancer cell growth by reducing COX-2 and VEGF expression and cell cycle arrest

Chemical and physical variations of cannabis smoke from a variety of cannabis samples in New Zealand

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