Dihydroartemisinin: A Potential Natural Anticancer Drug

Dai, Xiaoshuo; Zhang, Xiaoyan; Chen, Wei; Chen, Yihuan; Zhang, Qiushuang; Mo, Saijun; Lü, Jing

doi:10.7150/ijbs.50364

Cited by 124 publications

(81 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Artemisinin derivatives bear a peroxide-containing sesquiterpene lactone moiety and can produce highly reactive free radicals (peroxyl free radicals and ROS) in the presence of ferrous ions (Fe[II]) [ 63 , 64 ]. As tumor cells contain a much higher level of Fe[II] ions than healthy tissue cells, artemisinin derivatives can induce the formation of peroxyl free radicals and ROS and oxidative stress, DNA damage and selective apoptosis of cancer cells [ 65 ].…”

Section: Strategies Employed To Produce Anticancer Chalconesmentioning

confidence: 99%

Chalcone Derivatives: Role in Anticancer Therapy

et al. 2021

View full text Add to dashboard Cite

Chalcones (1,3-diaryl-2-propen-1-ones) are precursors for flavonoids and isoflavonoids, which are common simple chemical scaffolds found in many naturally occurring compounds. Many chalcone derivatives were also prepared due to their convenient synthesis. Chalcones as weandhetic analogues have attracted much interest due to their broad biological activities with clinical potentials against various diseases, particularly for antitumor activity. The chalcone family has demonstrated potential in vitro and in vivo activity against cancers via multiple mechanisms, including cell cycle disruption, autophagy regulation, apoptosis induction, and immunomodulatory and inflammatory mediators. It represents a promising strategy to develop chalcones as novel anticancer agents. In addition, the combination of chalcones and other therapies is expected to be an effective way to improve anticancer therapeutic efficacy. However, despite the encouraging results for their response to cancers observed in clinical studies, a full description of toxicity is required for their clinical use as safe drugs for the treatment of cancer. In this review, we will summarize the recent advances of the chalcone family as potential anticancer agents and the mechanisms of action. Besides, future applications and scope of the chalcone family toward the treatment and prevention of cancer are brought out.

show abstract

Section: Strategies Employed To Produce Anticancer Chalconesmentioning

confidence: 99%

Chalcone Derivatives: Role in Anticancer Therapy

et al. 2021

View full text Add to dashboard Cite

show abstract

“…This programmed cell death process is mediated by a variety [16,17]. Recent studies reported that DHA can significantly induce apoptosis of tumor cells [18]. Haiting Mao et al found that mitochondrial pathway played an important effect in the process of DHA-induced breast cancer cell apoptosis [19].…”

Section: Discussionmentioning

confidence: 99%

Novel dihydroartemisinin derivative Mito-DHA5 induces apoptosis associated with mitochondrial pathway in bladder cancer cells

Xiao

Lin

et al. 2022

BMC Pharmacol Toxicol

View full text Add to dashboard Cite

Background Bladder cancer is the second most common genitourinary malignancy and the eleventh most common cancer worldwide. Dihydroartemisinin (DHA), a first-line antimalarial drug, has been found to have potent antitumor activity. In our previous study, a novel dihydroartemisinin derivative Mito-DHA5 synthesized in our laboratory has a stronger anti-tumor activity than DHA. In this study, we investigated the apoptotic effect of Mito-DHA5 on bladder cancer T24 cells and molecular mechanisms underlying. Methods Antitumor activity in vitro was evaluated by MTT, wound healing and cloning formation assays. Mitochondrial membrane potential (MMP) was detected by JC-1 probe and ROS levels were measured by specific kit. The expression of caspase-3, cleaved-caspase3, mitochondrial Cyt-C, Bcl-2, Bax and PARP in T24 cells was evaluated by Western blotting. Results The results showed that Mito-DHA5 reduced cell viability with an IC50 value of 3.2 µM and induced T24 cell apoptosis in a dose-dependent manner, increased the production of ROS and decreased MMP. Mito-DHA5 could down-regulate the expression of Bcl-2, mitochondrial Cyt-C, Caspase-3, PARP and up-regulate the expression of Bax and cleaved Caspase-3. Conclusions These data suggested that Mito-DHA5 had a potent inhibitory effect on T24 bladder cancer cell growth and induced these cells apoptosis associated with mitochondrial pathway.

show abstract

“…These results indicated that DHA was a safe potential antitumor reagent with low toxicity. Besides the antimalaria activity, DHA has been reported to exhibit significant anticancer activity in a variety of tumors (Dai et al, 2021), including lung cancer (Jiang et al, 2016), ovarian cancer (Li et al, 2018), MM (Wu et al, 2020), and hepatocellular carcinoma (Zou et al, 2019). Previous study demonstrated that inhibition of telomerase activity could reduce the proliferation and migration of esophageal cancer cells (Li et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Human Telomerase Reverse Transcriptase as a Therapeutic Target of Dihydroartemisinin for Esophageal Squamous Cancer

Liu

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Objective: To elucidate the oncogenic role of human telomerase reverse transcriptase (hTERT) in esophageal squamous cancer and unravel the therapeutic role and molecular mechanism of dihydroartemisinin (DHA) by targeting hTERT.Methods: The expression of hTERT in esophageal squamous cancer and the patients prognosis were analyzed by bioinformatic analysis from TCGA database, and further validated with esophageal squamous cancer tissues in our cohort. The Cell Counting Kit-8 (CCK8) and colony formation assay were used to evaluate the proliferation of esophageal squamous cancer cell lines (Eca109, KYSE150, and TE1) after hTERT overexpression or treated with indicated concentrations of DHA. Transwell migration assay and scratch assay were employed to determine the migration abilities of cancer cells. Fluorescence microscopy and flow cytometry were conducted to measure the intracellular reactive oxygen species (ROS) levels in cancer cells after treated with DHA. Moreover, RT-PCR and Western blot were performed to test the alteration of associated genes on mRNA and protein level in DHA treated esophageal squamous cancer cell lines, respectively. Furthermore, tumor-bearing nude mice were employed to evaluate the anticancer effect of DHA in vivo.Results: We found that hTERT was significantly upregulated in esophageal squamous cancer both from TCGA database and our cohort also. Overexpression of hTERT evidently promoted the proliferation and migration of esophageal squamous cancer cells in vitro. Moreover, DHA could significantly inhibit the proliferation and migration of esophageal cancer cell lines Eca109, KYSE150, and TE1 in vitro, and significantly down-regulate the expression of hTERT on both mRNA and protein level in a time- and dose-dependent manner as well. Further studies showed that DHA could induce intracellular ROS production in esophageal cancer cells and down-regulate SP1 expression, a transcription factor that bound to the promoter region of hTERT gene. Moreover, overexpression of SP1 evidently promoted the proliferation and migration of Eca109 and TE1 cells. Intriguingly, rescue experiments showed that inhibiting ROS by NAC alleviated the downregulation of SP1 and hTERT in cells treated with DHA. Furthermore, overexpression of SP1 or hTERT could attenuate the inhibition effect of DHA on the proliferation and migration of Eca109 cells. In tumor-bearing nude mice model, DHA significantly inhibited the growth of esophageal squamous cancer xenografts, and downregulated the expression of SP1 and hTERT protein, while no side effects were observed from heart, kidney, liver, and lung tissues by HE stain.Conclusion: hTERT plays an oncogenic role in esophageal squamous cancer and might be a therapeutic target of DHA through regulating ROS/SP1 pathway.

show abstract

Dihydroartemisinin: A Potential Natural Anticancer Drug

Cited by 124 publications

References 112 publications

Chalcone Derivatives: Role in Anticancer Therapy

Chalcone Derivatives: Role in Anticancer Therapy

Novel dihydroartemisinin derivative Mito-DHA5 induces apoptosis associated with mitochondrial pathway in bladder cancer cells

Human Telomerase Reverse Transcriptase as a Therapeutic Target of Dihydroartemisinin for Esophageal Squamous Cancer

Contact Info

Product

Resources

About