Ferroptosis-centered Disease Response Information
General Information of the Disease (ID: DIS00013)
Name |
Multiple myeloma
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ICD |
ICD-11: 2A83
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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