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Oliva, Richard A.

doi:10.1016/0022-3913(80)90128-6

Cited by 5 publications

(5 citation statements)

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“…Notably, various antitumor, neuroprotective, and cardioprotective effects have been demonstrated for mdivi-1 30 , 34 – 36 , 60 – 62 , and its therapeutic value continues to be explored. Given the side effects of tubulin-targeting drugs, such as peripheral neuropathy 2 , 63 , our data warrant further evaluation of microtubule-associated mechanisms in the development of mdivi-1-based therapeutic strategies.…”

Section: Discussionmentioning

confidence: 90%

“…TNBC is the most refractory subtype of breast cancer, and it is associated with chemoresistance, disease recurrence, and metastasis 1 , 3 , 47 – 49 . Although the tubulin-targeting taxanes, such as taxol, have been widely applied as first-line chemotherapeutics for breast cancers, drug side effects and tumor chemoresistance have limited their clinical application 2 . Thus, various combinations of taxol with other drugs are being tested in a broad effort to improve the efficacy of taxol-based chemotherapy 1 , 2 .…”

Section: Discussionmentioning

confidence: 99%

“…Although the tubulin-targeting taxanes, such as taxol, have been widely applied as first-line chemotherapeutics for breast cancers, drug side effects and tumor chemoresistance have limited their clinical application 2 . Thus, various combinations of taxol with other drugs are being tested in a broad effort to improve the efficacy of taxol-based chemotherapy 1 , 2 . In this study, we found that mdivi-1 enhances the antimitotic effects of taxol and can induce cytotoxicity in a taxol-resistant TNBC cell line, MDA-MB-231-TR.…”

Section: Discussionmentioning

confidence: 99%

“…Standard chemotherapeutic regimens for breast cancers include the use of taxane compounds as monotherapies or in combination with other therapeutics 1 , 2 . The prototypical taxane, taxol, is known to target tubulin, stabilize microtubule polymerization and disrupt mitotic spindle assembly to exert its antimitotic and anti-proliferative effects; taxol has remained a first-line chemotherapeutic for numerous cancers since its identification decades ago 4 .…”

Section: Introductionmentioning

confidence: 99%

“…These resistance mechanisms not only lead to treatment failures but may also further drive cancer progression and disease recurrence, contributing to overall poor prognosis for patients 1 , 25 , 26 . Thus, treatment-limiting side effects and chemoresistance present significant obstacles in the clinical application of taxanes 2 , 27 .…”

Section: Introductionmentioning

confidence: 99%

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Mdivi-1 induces spindle abnormalities and augments taxol cytotoxicity in MDA-MB-231 cells

Fang,

Kuo,

Yuan

et al. 2021

Cell Death Discov.

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Taxol is a first-line chemotherapeutic for numerous cancers, including the highly refractory triple-negative breast cancer (TNBC). However, it is often associated with toxic side effects and chemoresistance in breast cancer patients, which greatly limits the clinical utility of the drug. Hence, compounds that act in concert with taxol to promote cytotoxicity may be useful to improve the efficacy of taxol-based chemotherapy. In this study, we demonstrated that mdivi-1, a putative inhibitor of mitochondrial fission protein Drp1, enhances the anticancer effects of taxol and overcomes taxol resistance in a TNBC cell line (MDA-MB-231). Not only did mdivi-1 induce mitotic spindle abnormalities and mitotic arrest when used alone, but it also enhanced taxol-induced antimitotic effects when applied in combination. In addition, mdivi-1 induced pronounced spindle abnormalities and cytotoxicity in a taxol-resistant cell line, indicating that it can overcome taxol resistance. Notably, the antimitotic effects of mdivi-1 were not accompanied by prominent morphological or functional alterations in mitochondria and were Drp1-independent. Instead, mdivi-1 exhibited affinity to tubulin at μM level, inhibited tubulin polymerization, and immediately disrupted spindle assembly when cells entered mitosis. Together, our results show that mdivi-1 associates with tubulin and impedes tubulin polymerization, actions which may underlie its antimitotic activity and its ability to enhance taxol cytotoxicity and overcome taxol resistance in MDA-MB-231 cells. Furthermore, our data imply a possibility that mdivi-1 could be useful to improve the therapeutic efficacy of taxol in breast cancer.

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