Improved Therapeutic Efficacy of Doxorubicin Chemotherapy With Cannabidiol in 4T1 Mice Breast Cancer Model
ABSTRACT Background High dose chemotherapy is one of the therapeutic strategies for breast cancer and doxorubicin (DOX) as a chemotherapy agent is widely used. DOX indication is limited due to its dose‐depended cardiotoxicity. Recently, cannabidiol (CBD) shows antitumoral and cardioprotective effect...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-11-01
|
| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.70395 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850192156650635264 |
|---|---|
| author | Koorosh Tabatabaei Sara Moazzezi Mohammadreza Emamgholizadeh Haleh Vaez Behzad Baradaran Behrooz Shokouhi |
| author_facet | Koorosh Tabatabaei Sara Moazzezi Mohammadreza Emamgholizadeh Haleh Vaez Behzad Baradaran Behrooz Shokouhi |
| author_sort | Koorosh Tabatabaei |
| collection | DOAJ |
| description | ABSTRACT Background High dose chemotherapy is one of the therapeutic strategies for breast cancer and doxorubicin (DOX) as a chemotherapy agent is widely used. DOX indication is limited due to its dose‐depended cardiotoxicity. Recently, cannabidiol (CBD) shows antitumoral and cardioprotective effects, so we hypothesized that CBD administration with high‐dose DOX chemotherapy can improve anticancer activity and reduce cardiotoxic side effects. Method Mice breast cancer model established by injecting 4T1 cell lines. One group was not injected by 4T1 cells as a not cancerous group and received normal saline (NS, 0.1 mL). In cancerous groups, first group was considered as cancerous control and received NS (0.1 mL); the second group received CBD (5 mg/kg, IP) on Days 1,7, and 14; in the third group DOX (5 mg/kg, IV) as CBD schedule was administrated; the fourth group treated with CBD 1 day before DOX injection as pretreatment, and the last group was treated with CBD and DOX at same time with previous doses and schedules. On Day 21, all mice were sacrificed, heart and lungs tissues were obtained and histological sections were isolated. SOD2, iNOS, MMP2, MMP9 were evaluated through western blot and TUNEL test preformed for breast tumor. Results Tumor size and weight significantly decreased in DOX, pretreatment CBD + DOX and CBD + DOX groups. Administration of CBD with DOX could not prevent weight loss. TUNEL test demonstrated the highest tumor cell apoptosis in pretreatment CBD + DOX and CBD + DOX. In lungs belonged to CBD + DOX, there was not any sign of metastasis. Cardiac histopathological examination of pretreatment CBD + DOX and CBD + DOX did not show any sign of congestion or inflammation. In CBD + DOX SOD2 increased, also iNOS, MMP2, and MMP9 decreased compared to DOX. Conclusions This study demonstrated that simultaneous administration of CBD and DOX can increase antitumoral effect and reduce DOX cardiotoxicity. Nevertheless, CBD can induce cardiotoxicity as administrated alone. |
| format | Article |
| id | doaj-art-ff58d3ea69c1471e91477ced55ab4878 |
| institution | OA Journals |
| issn | 2045-7634 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-ff58d3ea69c1471e91477ced55ab48782025-08-20T02:14:39ZengWileyCancer Medicine2045-76342024-11-011321n/an/a10.1002/cam4.70395Improved Therapeutic Efficacy of Doxorubicin Chemotherapy With Cannabidiol in 4T1 Mice Breast Cancer ModelKoorosh Tabatabaei0Sara Moazzezi1Mohammadreza Emamgholizadeh2Haleh Vaez3Behzad Baradaran4Behrooz Shokouhi5Student Research Committee Tabriz University of Medical Sciences Tabriz IranStudent Research Committee Tabriz University of Medical Sciences Tabriz IranStudent Research Committee Tabriz University of Medical Sciences Tabriz IranDepartment of Pharmacology and Toxicology, Faculty of Pharmacy Tabriz University of Medical Sciences Tabriz IranImmunology Research Center Tabriz University of Medical Sciences Tabriz IranDepartment of Pathology Tabriz University of Medical Sciences Tabriz IranABSTRACT Background High dose chemotherapy is one of the therapeutic strategies for breast cancer and doxorubicin (DOX) as a chemotherapy agent is widely used. DOX indication is limited due to its dose‐depended cardiotoxicity. Recently, cannabidiol (CBD) shows antitumoral and cardioprotective effects, so we hypothesized that CBD administration with high‐dose DOX chemotherapy can improve anticancer activity and reduce cardiotoxic side effects. Method Mice breast cancer model established by injecting 4T1 cell lines. One group was not injected by 4T1 cells as a not cancerous group and received normal saline (NS, 0.1 mL). In cancerous groups, first group was considered as cancerous control and received NS (0.1 mL); the second group received CBD (5 mg/kg, IP) on Days 1,7, and 14; in the third group DOX (5 mg/kg, IV) as CBD schedule was administrated; the fourth group treated with CBD 1 day before DOX injection as pretreatment, and the last group was treated with CBD and DOX at same time with previous doses and schedules. On Day 21, all mice were sacrificed, heart and lungs tissues were obtained and histological sections were isolated. SOD2, iNOS, MMP2, MMP9 were evaluated through western blot and TUNEL test preformed for breast tumor. Results Tumor size and weight significantly decreased in DOX, pretreatment CBD + DOX and CBD + DOX groups. Administration of CBD with DOX could not prevent weight loss. TUNEL test demonstrated the highest tumor cell apoptosis in pretreatment CBD + DOX and CBD + DOX. In lungs belonged to CBD + DOX, there was not any sign of metastasis. Cardiac histopathological examination of pretreatment CBD + DOX and CBD + DOX did not show any sign of congestion or inflammation. In CBD + DOX SOD2 increased, also iNOS, MMP2, and MMP9 decreased compared to DOX. Conclusions This study demonstrated that simultaneous administration of CBD and DOX can increase antitumoral effect and reduce DOX cardiotoxicity. Nevertheless, CBD can induce cardiotoxicity as administrated alone.https://doi.org/10.1002/cam4.70395breast cancercannabidiolcardiotoxicitydoxorubicinlung metastasis |
| spellingShingle | Koorosh Tabatabaei Sara Moazzezi Mohammadreza Emamgholizadeh Haleh Vaez Behzad Baradaran Behrooz Shokouhi Improved Therapeutic Efficacy of Doxorubicin Chemotherapy With Cannabidiol in 4T1 Mice Breast Cancer Model Cancer Medicine breast cancer cannabidiol cardiotoxicity doxorubicin lung metastasis |
| title | Improved Therapeutic Efficacy of Doxorubicin Chemotherapy With Cannabidiol in 4T1 Mice Breast Cancer Model |
| title_full | Improved Therapeutic Efficacy of Doxorubicin Chemotherapy With Cannabidiol in 4T1 Mice Breast Cancer Model |
| title_fullStr | Improved Therapeutic Efficacy of Doxorubicin Chemotherapy With Cannabidiol in 4T1 Mice Breast Cancer Model |
| title_full_unstemmed | Improved Therapeutic Efficacy of Doxorubicin Chemotherapy With Cannabidiol in 4T1 Mice Breast Cancer Model |
| title_short | Improved Therapeutic Efficacy of Doxorubicin Chemotherapy With Cannabidiol in 4T1 Mice Breast Cancer Model |
| title_sort | improved therapeutic efficacy of doxorubicin chemotherapy with cannabidiol in 4t1 mice breast cancer model |
| topic | breast cancer cannabidiol cardiotoxicity doxorubicin lung metastasis |
| url | https://doi.org/10.1002/cam4.70395 |
| work_keys_str_mv | AT kooroshtabatabaei improvedtherapeuticefficacyofdoxorubicinchemotherapywithcannabidiolin4t1micebreastcancermodel AT saramoazzezi improvedtherapeuticefficacyofdoxorubicinchemotherapywithcannabidiolin4t1micebreastcancermodel AT mohammadrezaemamgholizadeh improvedtherapeuticefficacyofdoxorubicinchemotherapywithcannabidiolin4t1micebreastcancermodel AT halehvaez improvedtherapeuticefficacyofdoxorubicinchemotherapywithcannabidiolin4t1micebreastcancermodel AT behzadbaradaran improvedtherapeuticefficacyofdoxorubicinchemotherapywithcannabidiolin4t1micebreastcancermodel AT behroozshokouhi improvedtherapeuticefficacyofdoxorubicinchemotherapywithcannabidiolin4t1micebreastcancermodel |