Artemisinin and Its Derivatives as Potential Anticancer Agents
Abstract
:1. Introduction
2. Chemical Features of Artemisinin and Its Representative Derivatives
3. Anticancer Effects of Artemisinin and Its Derivatives
3.1. Anticancer Effects of Artemisinin and Its Derived Monomers
3.1.1. Anticancer Effects on Breast Cancer
3.1.2. Anticancer Effects on Lung Cancer
3.1.3. Anticancer Effects on Liver Cancer
3.1.4. Anticancer Effects on Colorectal Cancer
3.1.5. Anticancer Effects on Melanoma
3.1.6. Anticancer Effects on Esophageal Cancer
3.1.7. Anticancer Effects on Other Cancers
3.2. Anticancer Effects of Artemisinin-Derived Dimers
3.3. Combination Therapy with Artemisinin and Its Derivatives against Cancer
3.4. Nanomedicine in Anticancer Therapy Using Artemisinin and Its Derivatives
4. Anticancer Mechanisms of Artemisinin and Its Derivatives
4.1. Cancer Proliferation and Metastasis
4.2. Angiogenesis
4.3. Cell Cycle
4.4. Cell Death
4.4.1. Apoptosis
4.4.2. Autophagy
4.4.3. Ferroptosis
4.4.4. Pyroptosis
4.4.5. Oncosis
4.5. Immunomodulation in Cancer
4.6. Glucose Metabolism
4.7. STAT3
4.8. Cancer Stem Cells
5. Clinical Trials of Artemisinin and Its Derivatives
6. Conclusion and Prospective
Author Contributions
Funding
Conflicts of Interest
References
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Compound | Cancer Type | Anticancer Effect | Mechanism | Ref. |
---|---|---|---|---|
Artemisinin | Prostate cancer | Inhibiting invasion and migration | Downregulating the E2F5/TFPI2/MMP pathway | [67] |
Thyroid cancer | Inhibiting anaerobic glycolysis | Downregulating the XIST/miR-93/HIF-1α pathway | [68] | |
Dihydroartemisinin | Bladder cancer | Inhibiting invasion and migration | Reducing KDM3A and inducing p21 | [69] |
Cervical cancer | Inducing ferroptosis | Inducing ferritinophagy | [70] | |
Inducing cell growth, invasion, migration, and apoptosis | Reducing Bcl-2, N-cadherin, and Vimentin; inducing RECK | [71] | ||
Gastric cancer | Inhibiting cell growth, invasion, and migration; inducing G1 cell cycle arrest | Downregulating the cyclin D1-CDK4-Rb pathway, PCNA, and MMP2 | [72] | |
Glioma | Inhibiting ferroptosis | Upregulating the TUG1/MAZ/FTH1 pathway | [73] | |
Head and neck cancer | Inducing ferroptosis | Inducing ROS production | [74] | |
Inducing invasion and migration | Regulating miR-195-5p expression | [75] | ||
Neuroblastoma | Inhibiting cell growth and inducing apoptosis | Regulating taurine, linoleic acid, phenylalanine metabolism, and tryptophan metabolism | [76] | |
Osteosarcoma | Inhibiting cell growth, inducing cell death | Inducing the ROS/Erk1/2 pathway and mitochondrial damage | [77] | |
Inhibiting angiogenesis | Reducing Loxl2/VEGFA expression | [78] | ||
Ovarian cancer | Inhibiting cell growth | / | [79] | |
Pancreatic cancer | Inducing ferroptosis | Regulating survival prediction-related genes | [80] | |
Prostate cancer | Inhibiting cell growth and migration, inducing apoptosis | Reducing UHRF1 and inducing p16 | [81] | |
Rhabdomyosarcoma | Inhibiting cell growth | Inhibiting the mTORC1 pathway by inducing the AMPK pathway | [82] | |
Artesunate | Bladder cancer | Inducing cell death | Inducing ROS production and activating the AMPK-mTOR-ULK1 pathway | [83] |
Insulinoma | Inducing ferroptosis | Downregulating the SLC7A11/GPX4 pathway | [84] | |
Lymphoma | Inhibiting cell growth, inducing G2/M cell cycle arrest and cell death | Inducing ROS production and TRF2 degradation | [85] | |
Inducing apoptosis, autophagy, and ferroptosis | Inhibiting the E2F5/TFPI2/MMP pathway | [86] | ||
Renal cancer | Inducing cell growth and cell death, inhibiting anaerobic glycolysis | Inducing ROS production and regulating P53 | [87] | |
Thyroid cancer | Inhibiting cell growth, invasion, and migration | Inhibiting the PI3K/Akt/FKHR pathway | [88] | |
Anhydrodihydroartemisinin (10) | Prostate cancer | Inhibiting cell growth and migration | Modulating the caspase-dependent pathway | [89] |
Compound | Aim | Target | Design a | Case/Control | Dose Regimen b | Duration | Main Outcome Measures c | Ref. |
---|---|---|---|---|---|---|---|---|
Artemisinin | Clinical effects and safety | Prostate cancer | CCT | 15/- | p.o., 300–400 mg, t.i.d. | 3 years | PSA doubling time, velocity, signs and symptoms of metastasis and survival | [109] |
Safety, tolerability, and pharmacokinetics | Advanced solid tumor malignancies | CCT | 19/- | i.v., 8, 12, 18, 25, 34, and 45 mg/kg, once a week | 21 days | MTD and DLTs, clinical activity as well as pharmacokinetic analysis | [110] | |
Artesunate | Clinical effects and safety | Colorectal cancer | RCT | 12/11 | p.o., 200 mg, q.d. | 14 days | Apoptosis proportion of cancer cells, tumor marker expression (VEGF, EGFR, c-Myc, CD31, Ki67, and p53), and clinical responses | [111] |
Safety and tolerability | Metastatic breast cancer | CCT | 23/- | p.o., 100, 150, 200 mg, q.d. | 4 weeks | DL-AEs as well as neurological and audiological complications, ECG, full blood count including reticulocytes, ALAT, ASAT, creatinine, NTproBNP, and troponin T | [112] | |
CCT | 13/- | p.o., up to 200 mg, q.d. | Up to 37 months | AEs (clinical neurological examination, audiological examinations, ECG, hematology, clinical chemistry, CA 15-3, liver ultrasound) | [113] | |||
CCT | 23/- | p.o., 100, 150, 200 mg, q.d. | 4 weeks | DL-AEs as well as laboratory assessments, neurological, cardiological, and audiological examinations | [108] | |||
Pharmacokinetics | Metastatic breast cancer | CCT | 23/- | p.o., 100, 150, 200 mg, q.d. | 3 weeks | The population pharmacokinetic properties of artesunate and dihydroartemisinin in plasma | [12] | |
Artenimol-R | Clinical effects and safety | Advanced cervical cancer | CCT | 10/- | p.o., 200 mg, q.d. | 21 days | Pain and vaginal discharge symptoms, biomarker expression (p53, EGFR, Ki-67, CD31, and CD71) in biopsies | [114] |
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Wen, L.; Chan, B.C.-L.; Qiu, M.-H.; Leung, P.-C.; Wong, C.-K. Artemisinin and Its Derivatives as Potential Anticancer Agents. Molecules 2024, 29, 3886. https://doi.org/10.3390/molecules29163886
Wen L, Chan BC-L, Qiu M-H, Leung P-C, Wong C-K. Artemisinin and Its Derivatives as Potential Anticancer Agents. Molecules. 2024; 29(16):3886. https://doi.org/10.3390/molecules29163886
Chicago/Turabian StyleWen, Luan, Ben Chung-Lap Chan, Ming-Hua Qiu, Ping-Chung Leung, and Chun-Kwok Wong. 2024. "Artemisinin and Its Derivatives as Potential Anticancer Agents" Molecules 29, no. 16: 3886. https://doi.org/10.3390/molecules29163886