Health Care Professional Information

Scientific Name
Ethenyl-1-methyl-2,4-bis(1-methyl ethenyl) cyclohexane
Clinical Summary

Beta-elemene is a volatile terpene found in botanicals such as celery, mint, and in many herbs used in traditional medicine. Whereas the purified form is generally not used as a dietary supplement because of poor absorption, many patients consume herbs high in beta-elemene in belief that they help cure cancer.

In vitro studies show anti-proliferative effects of beta-elemene in various cancer cells through cell-cycle arrest and induction of apoptosis (3) (4) (5) (16) (17) (19) (20). It also enhanced the activity of cisplatin against prostate cancer cells (18). The parenteral form of beta-elemene isolated from Rhizoma zedoariae, a type of ginger, has been studied in Asia and is reported to relieve pain, decrease the side effects of chemotherapy, and increase the quality of life in cancer patients. However, human trials conducted so far are of poor quality (1) (15).
More studies are needed to understand the safety and efficacy of this product.

Food Sources

Rhizoma zedoariae (E Zhu)
Curcuma aromatica (Wenyujin)

Purported Uses
  • Cancer Treatment
Mechanism of Action

In an erythroleukemic cell line, beta-elemene inhibited telomerase activity, which was enhanced in combination with cyclophosphamide (9). It also demonstrated anti-fibrotic effects, inducing decreases in plasma angiotensin II levels and angiotensin II receptor type 1 expression, reducing collagen formation in a liver fibrosis rat model (10). Beta-elemene also exhibits anti-inflammatory effects, with reduction in LPS-induced nitric oxide production and prostaglandin E2 by rat peritoneal macrophages (11).

Beta-elemene has been shown to affect cancer cells via different mechanisms. In an in vitro study, following administration of beta-elemene, leukemia cells were arrested in S/G2 phase and underwent apoptosis (2). The antiproliferative effects were dependent on p38 MAPK activation/phosphorylation, cell cycle arrest in G0/G1, and inhibition of tumor growth of glioblastoma cells (3). Beta-elemene also induced G2/M arrest in lung carcinoma cells and ovarian cancer cells by combined reduction of cell-cycle promoters Cdc2 and cyclin B1, and elevated cell cycle regulators p53 and p27 (4) (5). Derivatives of beta-elemene showed antiproliferative activity in human cervical carcinoma cells through a decrease in cell cycle protein Cyclin D1 and thus cell cycle suppression (14). Furthermore, beta-elemene may enhance the effects of chemotherapy and radiation. In non-small cell lung cancer cells, apoptosis was induced by increased expression of Bax and p-Bcl-2, decreased Bcl-2 and XIAP, and augmented cisplatin-induced increases in caspase activity (6). In another study, apoptosis response to the taxanes paclitaxel and docetaxel in lung carcinoma cells was enhanced with beta-elemene, through increases in cytochrome c, caspase activity, downregulation of Bcl-2, and altered cell membrane permeability (7). Beta-elemene combined with radiation induced apoptosis in lung adenocarcinoma cells, possibly by sensitizing cancer cells to radiation (8).

Pharmacokinetics

Beta-elemene is rapidly metabolized and excreted and has a short half-life, approximately half an hour. It was shown to be highly lipophilic, capable of crossing the blood-brain barrier, and reached peak levels in target tissues at 15 minutes with high concentrations found in heart, kidney, liver, brain, and lung. In rats, beta-elemene is bound extensively to plasma protein, and less than 2% of the original compound was recovered in bile, urine, and feces demonstrating that the compound is metabolized rapidly in the body (12).
Modified beta-elemene compounds have been synthesized to increase bioavailability while maintaining anti-tumor activity. Adding a hydrophilic group demonstrated increased solubility and antiproliferative activity in human cervix epithelioid carcinoma HeLa, gastric carcinoma and leukemia cells (13).

Herb-Drug Interactions
  • Chemotherapy: Beta-elemene may increase the activity of cisplatin and taxanes (6) (7).
  • Radiation: Beta-elemene may increase the effects of radiation (8).
Literature Summary and Critique

A review of randomized clinical trials of beta-elemene conducted between 1996 and 2005 shows that the trials are of poor methodology, with little allocation concealment and lack of statistical analysis (1) (15). Well designed studies are needed to determine the anticancer effects of beta-elemene.

References
  1. Peng X, Zhao Y, Liang X, et al. Assessing the quality of RCTs on the effect of beta-elemene, one ingredient of a Chinese herb, against malignant tumors. Contemp Clin Trials. Feb 2006;27(1):70-82.
  2. Zheng S, Yang H, Zhang S, et al. Initial study on naturally occurring products from traditional Chinese herbs and vegetables for chemoprevention. J Cell Biochem Suppl. 1997;27:106-112.
  3. Yao YQ, Ding X, Jia YC, et al. Anti-tumor effect of beta-elemene in glioblastoma cells depends on p38 MAPK activation. Cancer Lett. Jun 8 2008;264(1):127-134.
  4. Wang G, Li X, Huang F, et al. Antitumor effect of beta-elemene in non-small-cell lung cancer cells is mediated via induction of cell cycle arrest and apoptotic cell death. Cell Mol Life Sci. Apr 2005;62(7-8):881-893.
  5. Li X, Wang G, Zhao J, et al. Antiproliferative effect of beta-elemene in chemoresistant ovarian carcinoma cells is mediated through arrest of the cell cycle at the G2-M phase. Cell Mol Life Sci. Apr 2005;62(7-8):894-904.
  6. Li QQ, Wang G, Zhang M, et al. beta-Elemene, a novel plant-derived antineoplastic agent, increases cisplatin chemosensitivity of lung tumor cells by triggering apoptosis. Oncol Rep. Jul 2009;22(1):161-170.
  7. Zhao J, Li QQ, Zou B, et al. In vitro combination characterization of the new anticancer plant drug beta-elemene with taxanes against human lung carcinoma. Int J Oncol. Aug 2007;31(2):241-252.
  8. Hao Jiang SM, Jianguo Feng. In vitro study of radiosensitization by beta-Elemene in A549 cell line from adenocarcinoma of lung. Chinese-German Journal of Clinical Oncology. 2008;8(1):12-15.
  9. Wang Y, Fang MY, Jiang F, Peng HJ. [Effects of arsenic trioxide, ginseng saponin and beta-elemene on telomere-telomerase system in K562 cell line]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. Jun 2004;12(3):315-320.
  10. Zhu R, Yang L, Shen L, et al. ANG II-AT1 receptor pathway is involved in the anti-fibrotic effect of beta-elemene. J Huazhong Univ Sci Technolog Med Sci. Apr 2009;29(2):177-181.
  11. Lim SS, Shin KH, Ban HS, et al. Effect of the essential oil from the flowers of Magnolia sieboldii on the lipopolysaccharide-induced production of nitric oxide and prostaglandin E2 by rat peritoneal macrophages. Planta Med. May 2002;68(5):459-462.
  12. Wang K, Li Z, Chen Y, Su C. The pharmacokinetics of a novel anti-tumor agent, beta-elemene, in Sprague-Dawley rats. Biopharm Drug Dispos. Oct 2005;26(7):301-307.
  13. Xu L, Tao S, Wang X, et al. The synthesis and anti-proliferative effects of beta-elemene derivatives with mTOR inhibition activity. Bioorg Med Chem. Aug 1 2006;14(15):5351-5356.
  14.  Sun Y, Liu G, Zhang Y, et al. Synthesis and in vitro anti-proliferative activity of beta-elemene monosubstituted derivatives in HeLa cells mediated through arrest of cell cycle at the G1 phase. Bioorg Med Chem. Feb 1 2009;17(3):1118-1124.
  15. Rui D, Xiaoyan C, Taixiang W, Guanjian L. Elemene for the treatment of lung cancer. Cochrane Database of Systematic Reviews. 2007(4):1-13.
  16. Zhu T, Xu Y, Dong B, et al. Beta-elemene inhibits proliferation of human glioblastoma cells through the activation of glia maturation factor â and induces sensitization to cisplatin. Oncol Rep. 2011 Apr 20. doi: 10.3892/or.2011.1276. [Epub ahead of print]
  17. Yu Z, Wang R, Xu L, et al. Beta-Elemene piperazine derivatives induce apoptosis in human leukemia cells through downregulation of c-FLIP and generation of ROS. PLoS One. 2011 Jan 25;6(1):e15843.
  18. Li QQ, Wang G, Reed E, Huang L, Cuff CF. Evaluation of Cisplatin in Combination with beta-Elemene as a Regimen for Prostate Cancer Chemotherapy. Basic Clin Pharmacol Toxicol. 2010 Apr 23. [Epub ahead of print]
  19. Li QQ, Wang G, Huang F, Banda M, Reed E. Antineoplastic effect of beta-elemene on prostate cancer cells and other types of solid tumour cells. J Pharm Pharmacol. 2010 Aug;62(8):1018-27.
  20. Chen W, Lu Y, Wu J, et al. Beta-elemene inhibits melanoma growth and metastasis via suppressing vascular endothelial growth factor-mediated angiogenesis. Cancer Chemother Pharmacol. 2011 Apr;67(4):799-808. Epub 2010 Jun 19.

Consumer Information

How It Works

Bottom line: Beta-elemene has shown anticancer activity in laboratory studies. More research is needed to study its effects in humans.

Beta-elemene is a compound found in plants such as celery, mint, and in many others used in traditional medicine. Although the pure form is not used as dietary supplement, some cancer patients use herbs high in beta-elemene as treatment. Beta-elemene was shown to prevent growth of cancer cells in laboratory cells by different mechanisms. A few poorly designed studies done in humans showed that it may improve quality of life in cancer patients. It is unclear if raw herbs containing beta-elemene have the same effects in humans. More research is needed.

Purported Uses
  • Cancer Treatment
    Laboratory studies indicate that beta-elemene can stop the growth of cancer cells. A few studies have been done in humans but the results are not reliable. Well designed clinical trials are needed.
Research Evidence

Well-designed clinical trials of beta-elemene have not been conducted in humans.

Do Not Take If
  • You are undergoing chemotherapy: Beta-elemene may increase the toxicity of chemo drugs, cisplatin and taxanes.
  • You are undergoing radiotherapy: Beta-elemene may increase the adverse effects of radiation.
E-mail your questions and comments to aboutherbs@mskcc.org.