General Information of the Disease (ID: DIS00013)
Name
Multiple myeloma
ICD
ICD-11: 2A83
Full List of Target(s) of This Ferroptosis-centered Disease
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Multiple myeloma [ICD-11: 2A83.1]
Responsed Drug Andrographis Approved
Responsed Regulator Mitogen-activated protein kinase 14 (MAPK14) Driver
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model RPMI-8226 cells Plasma cell myeloma Homo sapiens CVCL_0014
U266B1 cells Plasma cell myeloma Homo sapiens CVCL_0566
AML12 cells Normal Mus musculus CVCL_0140
Response regulation Andrographolide (Andro) may block the Nrf2/HO-1 signaling pathway by activating P38 ( MAPK14), thereby inducing ferroptosis. Moreover, inhibition of P38 expression rescued Andro-induced cell death, changes in the level of Nrf2 and HO-1 expression, Fe2+ and lipid peroxidation. Taken together, our findings suggest that Andro induces ferroptosis in Multiple myeloma (MM) cells via the P38/Nrf2/HO-1 pathway, providing a potential preventative and therapeutic approach for MM.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Multiple myeloma [ICD-11: 2A83.1]
Responsed Drug Andrographis Approved
Responsed Regulator Mitogen-activated protein kinase 14 (MAPK14) Driver
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model RPMI-8226 cells Plasma cell myeloma Homo sapiens CVCL_0014
U266B1 cells Plasma cell myeloma Homo sapiens CVCL_0566
AML12 cells Normal Mus musculus CVCL_0140
Response regulation Andrographolide (Andro) may block the Nrf2/HO-1 signaling pathway by activating P38 (MAPK14), thereby inducing ferroptosis. Moreover, inhibition of P38 expression rescued Andro-induced cell death, changes in the level of Nrf2 and HO-1 expression, Fe2+ and lipid peroxidation. Taken together, our findings suggest that Andro induces ferroptosis in Multiple myeloma (MM) cells via the P38/Nrf2/HO-1 pathway, providing a potential preventative and therapeutic approach for MM.
Heme oxygenase 1 (HMOX1)
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Multiple myeloma [ICD-11: 2A83.1]
Responsed Drug Andrographis Approved
Responsed Regulator Mitogen-activated protein kinase 14 (MAPK14) Driver
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model RPMI-8226 cells Plasma cell myeloma Homo sapiens CVCL_0014
U266B1 cells Plasma cell myeloma Homo sapiens CVCL_0566
AML12 cells Normal Mus musculus CVCL_0140
Response regulation Andrographolide (Andro) may block the Nrf2/HO-1 signaling pathway by activating P38 ( MAPK14), thereby inducing ferroptosis. Moreover, inhibition of P38 expression rescued Andro-induced cell death, changes in the level of Nrf2 and HO-1 expression, Fe2+ and lipid peroxidation. Taken together, our findings suggest that Andro induces ferroptosis in Multiple myeloma (MM) cells via the P38/Nrf2/HO-1 pathway, providing a potential preventative and therapeutic approach for MM.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Multiple myeloma [ICD-11: 2A83.1]
Responsed Drug Andrographis Approved
Responsed Regulator Mitogen-activated protein kinase 14 (MAPK14) Driver
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model RPMI-8226 cells Plasma cell myeloma Homo sapiens CVCL_0014
U266B1 cells Plasma cell myeloma Homo sapiens CVCL_0566
AML12 cells Normal Mus musculus CVCL_0140
Response regulation Andrographolide (Andro) may block the Nrf2/HO-1 signaling pathway by activating P38 (MAPK14), thereby inducing ferroptosis. Moreover, inhibition of P38 expression rescued Andro-induced cell death, changes in the level of Nrf2 and HO-1 expression, Fe2+ and lipid peroxidation. Taken together, our findings suggest that Andro induces ferroptosis in Multiple myeloma (MM) cells via the P38/Nrf2/HO-1 pathway, providing a potential preventative and therapeutic approach for MM.
Cystine/glutamate transporter (SLC7A11)
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Suppressor
Responsed Disease Multiple myeloma [ICD-11: 2A83.1]
Responsed Drug Fingolimod Investigative
Responsed Regulator 5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
AMPK signaling pathway hsa04152
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model U266B1 cells Plasma cell myeloma Homo sapiens CVCL_0566
RPMI-8226 cells Plasma cell myeloma Homo sapiens CVCL_0014
Response regulation Multiple myeloma (MM) is the second hematological plasma cell malignany and sensitive to fingolimod (FTY720), a novel immunosuppressant. Fingolimod (FTY720) can activate PP2A subunit C and dephosphorylate AMPKa, and then inhibit the expression of SLC7A11 and GPX4. In conclusion, FTY720 induces ferroptosis and autophagy through the PP2A/AMPK pathway.
Unspecific Target
In total 3 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [3]
Responsed Disease Multiple myeloma [ICD-11: 2A83.1]
Responsed Drug Nitidine chloride Investigative
Responsed Regulator ATP-binding cassette sub-family B member 6 (ABCB6) Suppressor
Pathway Response PI3K-Akt signaling pathway hsa04151
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model U266B1 cells Plasma cell myeloma Homo sapiens CVCL_0566
RPMI-8226 cells Plasma cell myeloma Homo sapiens CVCL_0014
Sp2/0-Ag14 cells Plasma cell myeloma Mus musculus CVCL_2199
In Vivo Model
Male BALB/c nude mice, aged 5 weeks, were procured from Guangzhou Ruige biology Model Animal Research Center (No. 44827200001656, Guangzhou, China). Tumor xenograft assay was performed by dissolving SP2/0 cells in PBS (1 x 106/200 uL) and subcutaneously inoculating them into the right flank of mice. After the tumor reached 50 mm3, the tumor-bearing mice were randomly separated into three groups and intraperitoneally administered with NC (4.6 or 6 mg/kg) every two days. Body masses and tumor sizes were determined every day. Subsequently, the mice were sacrificed, and the inhibition of tumor growth and the tumor masses were determined. Later, visceral organs and tumors from every group were harvested and immobilized in paraformaldehyde (4%). All murine experimental procedures conformed to the National Institute of Health Guide for the Care and Use of Laboratory Animals.

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Response regulation Mechanistically, the direct binding of Nitidine chloride (NC) to ABCB6 suppressed PI3K/AKT signaling pathway to promote ferroptosis. In conclusion, ABCB6 can be a potential therapeutic target and prognostic biomarker in Multiple myeloma (MM), while NC can be considered a novel drug for MM treatment.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [4]
Responsed Disease Multiple myeloma [ICD-11: 2A83.1]
Responsed Drug Ginsenoside Rh4 Investigative
Responsed Regulator NAD-dependent protein deacetylase sirtuin-2 (SIRT2) Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell proliferation
Cell apoptosis
Cell cycle
In Vitro Model NCI-H929 cells Plasma cell myeloma Homo sapiens CVCL_1600
Response regulation Ginsenoside Rh4 inhibited SIRT2 expression in multiple myeloma (MM) cells. The overexpression of SIRT2 reversed the effects of ginsenoside Rh4 on cell proliferation, cell apoptosis, cycle arrest and ferroptosis in MM. Overall, ginsenoside Rh4 inhibited the malignant progression of MM and induced ferroptosis by regulating SIRT2.
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target [5]
Responsed Disease Multiple myeloma [ICD-11: 2A83.1]
Responsed Drug T. vulgaris and A. lappa Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell autophagy
Cell proliferation
In Vitro Model MOLP-8 cells Plasma cell myeloma Homo sapiens CVCL_2124
NCI-H929 cells Plasma cell myeloma Homo sapiens CVCL_1600
RPMI-8226 cells Plasma cell myeloma Homo sapiens CVCL_0014
KMS-12-BM cells Plasma cell myeloma Homo sapiens CVCL_1334
KMS11 cells Plasma cell myeloma Homo sapiens CVCL_2989
L-363 cells Plasma cell myeloma Homo sapiens CVCL_1357
JJN-3 cells Plasma cell myeloma Homo sapiens CVCL_2078
AMO1 cells Plasma cell myeloma Homo sapiens CVCL_1806
OPM-2 cells Plasma cell myeloma Homo sapiens CVCL_1625
NCI-H929 cells Plasma cell myeloma Homo sapiens CVCL_1600
Response regulation T. vulgaris and A. lappa could be considered as potential herbal drug candidates, which arrest multiple myeloma cancer cell proliferation by induction of apoptosis, autophagic, and ferroptosis.
References
Ref 1 Andrographolide induced ferroptosis in multiple myeloma cells by regulating the P38/Nrf2/HO-1 pathway. Arch Biochem Biophys. 2023 Jul 1;742:109622. doi: 10.1016/j.abb.2023.109622. Epub 2023 May 10.
Ref 2 FTY720 induces ferroptosis and autophagy via PP2A/AMPK pathway in multiple myeloma cells. Life Sci. 2020 Nov 1;260:118077. doi: 10.1016/j.lfs.2020.118077. Epub 2020 Aug 15.
Ref 3 Targeting ABCB6 with nitidine chloride inhibits PI3K/AKT signaling pathway to promote ferroptosis in multiple myeloma. Free Radic Biol Med. 2023 Jul;203:86-101. doi: 10.1016/j.freeradbiomed.2023.04.003. Epub 2023 Apr 10.
Ref 4 Ginsenoside Rh4 inhibits the malignant progression of multiple myeloma and induces ferroptosis by regulating SIRT2. Clin Exp Pharmacol Physiol. 2023 Sep;50(9):757-765. doi: 10.1111/1440-1681.13805. Epub 2023 Jul 15.
Ref 5 Induction of Apoptosis, Autophagy and Ferroptosis by Thymus vulgaris and Arctium lappa Extract in Leukemia and Multiple Myeloma Cell Lines. Molecules. 2020 Oct 29;25(21):5016. doi: 10.3390/molecules25215016.