Development of artemisinin compounds for cancer treatment

Abstract

Artemisinin contains an endoperoxide moiety that can react with iron to form cytotoxic free radicals. Cancer cells contain significantly more intracellular free iron than normal cells and it has been shown that artemisinin and its analogs selectively cause apoptosis in many cancer cell lines. In addition, artemisinin compounds have been shown to have anti-angiogenic, anti-inflammatory, anti-metastasis, and growth inhibition effects. These properties make artemisinin compounds attractive cancer chemotherapeutic drug candidates. However, simple artemisinin analogs are less potent than traditional cancer chemotherapeutic agents and have short plasma half-lives, and would require high dosage and frequent administration to be effective for cancer treatment. More potent and target-selective artemisinin-compounds are being developed. These include artemisinin dimers and trimers, artemisinin hybrid compounds, and tagging of artemisinin compounds to molecules that are involved in the intracellular iron-delivery mechanism. These compounds are promising potent anticancer compounds that produce significantly less side effect than traditional chemotherapeutic agents.

Treatment of CMV infection after allogeneic hematopoietic stem cell transplantation

“…Unfortunately, there is not yet a thorough evaluation of its efficacy but only sporadic reports of its in vivo anti CMV activity with contrasting results [57]. Interesting insights come from artemisinin-derived dimers, novel compounds with more potent in vitro anti-CMV effects [58,59] the efficacy of which remains to be addressed.…”

A Glimpse into the Biosynthesis of Terpenoids

“…Artemisinin commercial production still largely relies on extraction from its natural source making ACTs more expensive than other less effective malaria treatments. Hence, research into creating microbial cell factories for sustainable production of artemisinin is of great importance [20,21,24].…”

Phospho-TCTP and Dihydroartemisinin: A Novel Therapeutic Opportunity in Advance Breast Cancer

“…Beyond the "anti-malarial effect", these pharmacological compounds show antitumor properties as well [16]. Despite the molecular mechanisms underlying their cytotoxic effect is not clearly elucidated, these compounds are selectively cytotoxic to cancer cells, as shown by both in vitro and in vivo evidence [17]. One mechanism that has been suggested is that the highly reactive endoperoxide moiety of Artemisinin is activated by an iron source (in the form of Fe +2 or heme, or both) to produce reactive oxygen species (ROS) [18].Molecular and epidemiological evidence show that iron metabolism is altered in many human cancers, including breast, colorectal, prostate, lung cancer and hepatocellular carcinoma [19], thereby making them more vulnerable to the cytotoxic effect of DHA compared to normal tissue.…”

“…One mechanism that has been suggested is that the highly reactive endoperoxide moiety of Artemisinin is activated by an iron source (in the form of Fe +2 or heme, or both) to produce reactive oxygen species (ROS) [18].Molecular and epidemiological evidence show that iron metabolism is altered in many human cancers, including breast, colorectal, prostate, lung cancer and hepatocellular carcinoma [19], thereby making them more vulnerable to the cytotoxic effect of DHA compared to normal tissue. Moreover, promising results obtained from in vivo studies (xenograft tumors) in various tumors, such as colorectal or hepatocellular carcinoma [17], have provided the rationale for the design of clinical studies. Today, phase I clinical trials of Artesunate (ARS), are conducted in patients with hepatocellular carcinoma (https://clinicaltrials.gov/ct2/show/NCT02304289), and with colorectal cancer (CRC) (http://www.controlled -trials.com/ISRCTN05203252).…”

“…In this context of iron dysregulation, DHA-toxicity may be enhanced, and may cause a severe oxidative stress leading to apoptosis in aggressive glioma cells. The potential therapeutic application of DHA for GMB is suggested by many findings showing that: i) DHA potentiates the cytotoxic effects of Temozolomide, a chemotherapy drug commonly used in treating patients with malignant brain tumors [17]; ii) DHA reduces Hypoxia-inducible factor 1 alpha (HIF-1α) expression and its target gene protein, vascular endothelial growth factor (VEGF) [17]; iii) DHA enhances radiosensitivity of human glioma cells in vitro [23]. Notably, high TCTP expression in glioma was significantly associated with advanced pathological grade, and Kaplan-Meir analysis showed that patients with glioma and higher TCTP expression tend to have shorter overall survival time [5].…”