Research Progress of Indole Alkaloids: Targeting MAP Kinase Signaling Pathways in Cancer Treatment
Abstract
:Simple Summary
Abstract
1. Introduction
2. MAPK Signaling Pathway in Cancer
3. Indole Alkaloids Targeting MAPK in Cancers
3.1. Evodiamine
3.2. Vinorelbine
3.3. Hirsutine
3.4. Fumigaclavine C
3.5. Flavopereirine
3.6. Evodiagenine
3.7. 3,3′-Diindolylmethane
3.8. Idole-3-Carbinol
3.9. Notoamide G
3.10. Vinblastine
3.11. Vincristine
3.12. Sclerotiamides C
3.13. Ellipticine
3.14. Chaetoglobosin K
3.15. Jerantinine B
3.16. Harmalacidine
3.17. L20
3.18. 11-Methoxytabersonine
3.19. Calothrixin A
3.20. Harmol
3.21. Chaetoglobosin G
3.22. 3α-Acetonyltabersonine
3.23. Isomahanine
3.24. Dehydrocrenatidine
4. Clinical Trials
5. Toxicity and Adverse Effects
6. Conclusions and Future Perspective
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Compounds | Cancer Type | Findings | Ref. |
---|---|---|---|
Evodiamine | Breast cancer | The p38 MAPK and ERK pathways are controlled by evodiamine. | [37] |
Colon cancer | JNK activation induces apoptosis triggered by evodiamine | [39] | |
Pancreatic cancer | Evodiamine dose-dependently stopped AKT, ERK1/2, and P38-MAPK phosphorylation. | [40] | |
Ovarian cancer | When evodiamine is present, PI3K/Akt, p38 MAPK, and ERK1/2 MAPK activation may result in cell death. | [41] | |
Skin cancer | Evodiamine induced caspase-mediated apoptosis and necrosis through the activation of p38 and ERK MAPK. | [42] | |
Bladder cancer | When evodiamine was added to 5637 and HT1197 cells, the P38-MAPK and some of the JNK pathways became more active while ERK pathway only became less active in 5637 cells. | [43] | |
Neural cancer | Glioma cells are destroyed by evodiamine via autophagy triggered by intracellular calcium/JNK signaling and apoptosis triggered by calcium/mitochondria. | [44] | |
Lung cacner | p-ERK and ERK-MAPK expression was inhibited by evodiamine. | [45] | |
Vinorelbine | Breast cancer | Vinorelbine increased P38-MAPK activity in breast cancer cells MCF-7 and MDA-MB-468. | [46] |
Hirsutine | Breast cancer | In addition to activating the p38-MAPK pathway, DNA damage signaling was induced in MDA-MB-453 cells | [47] |
Fumigaclavine C | Breast cancer | Fumigaclavine C dose-dependently reduced JNK, ERK 1/2, and P38-MAPK phosphorylation. | [48] |
Flavopereirine | Breast cancer | Flavopereirine causes MDA-MB-231 cell death via cell cycle arrest and AKT/P38-MAPK signaling pathway. | [49] |
Colon cancer | Flavopereirine elicited a decrease in cellular viability, impeded progression of the cell cycle, and prompted apoptosis via P53 signaling. | [50] | |
Evodiagenine | Breast cancer | Evodiagenine may inhibit PI3K/AKT/mTOR and increase P38-MAPK phosphorylation to cause photocytotoxicity | [51] |
3,3′-Diindolylmethane | Gastric cancer | 3,3′-diindolylmethane inhibits gastric cancer proliferation and triggers apoptosis via altering the TRAF2/p38-MAPK signaling pathway. | [52] |
Cervical cancer | The MAPK and PI3K signaling pathways have been shown to be involved in 3,3′-Diindolylmethane’s pro-apoptotic actions on cervical cancer cells. | [53] | |
Prostate cancer | 3,3′-Diindolylmethane as an indole capable of eliciting p75NTR-dependent apoptosis in prostate cancer cells via the p38-MAPK pathway. | [54] | |
Prostate cancer | In DU145 cells, 3,3′-diindolylmethane activates the p38-MAPK pathway in order to activate p27Kip1 and stop the cell cycle in G1. | [55] | |
Idole-3-carbinol | Hepatocellular cancer | Indole-3-carbinol may inhibit the hepatic stellate cell growth by blocking the NADPH oxidase/ROS/p38-MAPK pathway. | [56] |
Notoamide G | Hepatocellular cancer | Notoamide G triggered a P38/JNK pathway, which resulted in the induction of apoptosis and autophagy | [57] |
Vincristine | Cervical cancer | Vincristine caused a mitotic arrest, and only the cells that were experiencing a mitotic arrest had p38-MAPK active. | [58] |
Skin cancer | Apoptosis produced by vincristine is JNK/MAPK activation dependent in at least some melanoma cell lines. | [59] | |
Vinblastine | Cervical cancer | Vinblastine induced mitotic arrest and selectively activated p38-MAPK in mitotically arrested cells. | [58] |
Sclerotiamides C | Cervical cancer | Sclerotiamide C has been observed to prompt apoptosis in HeLa cells through the mechanisms of cell cycle arrest, ROS production activation, and regulation of proteins related to apoptosis within the MAPK signaling pathway. | [60] |
Ellipticine | Endometrial cancer | In RL95-2 cells, apoptosis can be induced by ellipticine through ROS and the MAPKs activation | [61] |
Chaetoglobosin K | Ovarian cancer | Chaetoglobosin K increased P38-MAPK phosphorylation in ovarian cancer cells, causing G2 arrest through cyclin B1 and death | [62] |
Jerantinine B | Leukemia | Jerantinine B caused cell death, and phospho-kinase arrays revealed increased and activated total and phosphorylated c-Jun/JNK (S63) levels. | [63] |
Harmalacidine | Leukemia | Harmalacidine’s cytotoxic action targeted mitochondrial and PTKs-Ras/Raf/ERK pathways. | [64] |
L20 | Leukemia | Through damaging DNA and p38-MAPK pathway modification, L20 caused mitochondrial driven apoptosis and G2/M arrest | [65] |
11-Methoxytabersonine | Lung cancer | The autophagy induced by 11-methoxytabersonine was discovered to occur through the activation of JNK signaling systems. | [66] |
Calothrixin A | Lung cancer | Calothrixin A acted against lung cancer by blocking Topo I. This caused the cell cycle to stop and the cells to move, as well as apoptosis and autophagy through the PI3K/Akt/JNK/p53 pathway. | [67] |
Harmol | Lung cancer | MEK/ERK inhibitor U0126 stopped autophagy in part by blocking the ERK1/2 pathway. | [68] |
Chaetoglobosin G | Lung cancer | Chaetoglobosin G clearly stopped the growth of A549 cells, and it may have done this by causing autophagy in A549 cells via the ERK pathway to increase the production of P21. | [69] |
3α-acetonyltabersonine | Neural cancer | 3α-acetonyltabersonine hindered DNA damage repair, causing MAPK pathway activation and apoptosis | [70] |
Isomahanine | Oral cancer | Isomahanine has been found to elicit endoplasmic reticulum stress, leading to the activation of both p38 MAPK-mediated apoptosis and autophagy | [71] |
Dehydrocrenatidine | Oral cacner | The induction of apoptosis by Dehydrocrenatidine was observed through the stimulation of ERK and c-JNK. | [72] |
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Al Amin, M.; Emran, T.B.; Khan, J.; Zehravi, M.; Sharma, I.; Patil, A.; Gupta, J.K.; Jeslin, D.; Krishnan, K.; Das, R.; et al. Research Progress of Indole Alkaloids: Targeting MAP Kinase Signaling Pathways in Cancer Treatment. Cancers 2023, 15, 5311. https://doi.org/10.3390/cancers15225311
Al Amin M, Emran TB, Khan J, Zehravi M, Sharma I, Patil A, Gupta JK, Jeslin D, Krishnan K, Das R, et al. Research Progress of Indole Alkaloids: Targeting MAP Kinase Signaling Pathways in Cancer Treatment. Cancers. 2023; 15(22):5311. https://doi.org/10.3390/cancers15225311
Chicago/Turabian StyleAl Amin, Md., Talha Bin Emran, Jishan Khan, Mehrukh Zehravi, Indu Sharma, Anasuya Patil, Jeetendra Kumar Gupta, D. Jeslin, Karthickeyan Krishnan, Rajib Das, and et al. 2023. "Research Progress of Indole Alkaloids: Targeting MAP Kinase Signaling Pathways in Cancer Treatment" Cancers 15, no. 22: 5311. https://doi.org/10.3390/cancers15225311