Curcumin and Vinblastine Disturb Ectonucleotides Enzymes Activity and Promote ROS Production in Human Cutaneous Melanoma Cells

HIGHLIGHTS

• Melanoma is a cancer with poor prognosis, and metastasis.

• Curcumin is a compound with many beneficial effects regarding prevention and adjuvant treatment of cancer

• Vinblastine and curcumin greatly promoted production of ROS in melanoma cells

• Curcumin disrupted adenosine formation cascade, reducing imunosupression at tumoral site.

Abstract

Cancer is the leading cause of death. Melanoma skin cancer originates in melanocytes and represents 80% of the deaths associated with skin cancer. Vinblastine (VIN) is a chemotherapeutic agent used in the treatment of cancer through disrupting mitotic spindle and tumor development. Curcumin (CUR), a compound extracted from the rhizomes of the Curcuma longa plant, has beneficial effects in preventing the development and progression of cancer while modulating the immune response and oxidative stress. The expression of purinergic receptors, ecto-enzymes, and adenosine can modulate the inflammatory responses in cancer. The activity of enzymes, the markers of cell damage in oxidative stress, the generation of reactive oxygen species (ROS), and the activities of ecto-enzymes in the melanoma cell line were investigated. The human melanoma cell line was treated with curcumin (40 µM), vinblastine (VIN) (20 nM), or a combination of both for 24h. Oxidative stress enzymes and byproducts were measured and compared against the activity of ecto-enzymes. There was a marked increase in ROS production in all groups, but an increase in protein carbonylation was only detected in the VIN group. CUR had an inhibitory effect on extracellular ADP hydrolysis, as evidenced by a significant decrease in ADP substrate removal. VIN possibly increased adenosine formation, as demonstrated by an increase in ADP substrate removal. VIN (alone or in combination with CUR) reduced the activity of ADA, thus increasing the concentration of adenosine in the tumor microenvironment. CUR increased ROS generation in melanoma cells and disrupted the purinergic signaling cascade. Therefore, it may be a promising adjuvant therapy for melanoma, a cancer with a high incidence and lethality.

Keywords:
melanoma; curcumin; skin; enzymes; adjuvant; treatment.