From chemotherapy to oncoviruses – modern methods of treatment in metastatic melanoma

Drobek, Hanna H.; Bergler‐Czop, Beata; Miziołek, Bartosz

doi:10.5114/dr.2017.69947

Cited by 1 publication

(1 citation statement)

References 29 publications

(175 reference statements)

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“…The primary treatment for most melanomas is surgery (Miller et al 2016) or chemotherapy with dacarbazine and/or ipilimumab; additionally, a combination of vemurafenib and ipilimumab is recommended as first-line treatment depending on type of BRAF (B-Raf proto-oncogene) gene mutation of patients (Harries et al 2016). Unfortunately, side effects such as nausea, vomiting, weight loss, decreased appetite, headache, fatigue, pyrexia, and insomnia may occur during melanoma chemotherapy (Drobek et al 2017). Interestingly, perphenazine and prochlorperazine not only possess sedative, antiemetic (Motohashi et al 2006;Sudeshna and Parimal 2010), and anticancer activity but also modify multidrug resistance (Girly et al 2014;Jaszczyszyn et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Antimelanoma activity of perphenazine and prochlorperazine in human COLO829 and C32 cell lines

Otręba

Pajor

Warncke

2019

Naunyn-Schmiedeberg's Arch Pharmacol

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Cutaneous melanoma is least common (only about 1% of skin cancers) but is the deadliest malignant tumor. Moreover, amelanotic types of melanoma are very difficult for clinical diagnosis. The standard therapy can cause a lot of side effects, e.g., nausea, vomiting, and headaches, which means that novel and effective strategies are required. Interestingly, phenothiazine derivatives possess sedative, antiemetic, and anticancer activity. Our goal was to determine the effect of perphenazine and prochlorperazine on cell viability, motility, microphthalmia-associated transcription factor (MITF) and tyrosinase content in melanotic and amelanotic melanoma cells. The viability of C32 and COLO829 melanoma cells was evaluated by the WST-1 colorimetric assay; impact on motility of human melanoma was performed by wound-healing assay, while tyrosinase and MITF content were determined by Western blot. In the present study, we explore the anticancer effect of perphenazine and prochlorperazine in human melanotic (COLO829) and amelanotic (C32) melanoma cells concluding that prochlorperazine inhibits cell viability in a concentration-dependent manner, impairs motility, and decreases tyrosinase and MITF amounts. Moreover, the analyzed drugs decrease/increase MITF amount depending on the type of melanoma. We demonstrated that the decrease of MITF and tyrosinase protein induces motility inhibition of C32 cells, which suggests the ability of those drugs to restore cancer cell sensitivity to treatment. The ability of prochlorperazine to contain the spread of the amelanotic melanoma in vivo may be helpful in the development of a new and effective antimelanoma therapies.

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