Abstract
A herbal formula (SL) comprising Sophorae Flos and Lonicerae Japonicae Flos was traditionally used to treat melanoma. Constitutively active signal transducer and activator of transcription 3 (STAT3) has been proposed as a therapeutic target in melanoma. Here we investigated whether an ethanolic extract of SL (SLE) exerted anti-melanoma activities by inhibiting STAT3 signaling. B16F10 allograft model, A375 and B16F10 cells were employed to assess the in vivo and in vitro anti-melanoma activities of SLE. A375 cells stably expressing STAT3C, a constitutively active STAT3 mutant, were used to determine the role of STAT3 signaling in SLE’s anti-melanoma effects. Intragastric administration of SLE (1.2 g/kg) potently inhibited melanoma growth in mice and inhibited STAT3 phosphorylation in the tumors. In cultured cells, SLE dramatically reduced cell viability, induced apoptosis, suppressed migration and invasion, and restrained STAT3 activation and nuclear localization. STAT3C overexpression in A375 cells diminished SLE’s effects on cell viability, apoptosis and invasion. Collectively, SLE exerted potent anti-melanoma effects partially by inhibiting STAT3 signaling. This study provides pharmacological justification for the traditional use of this formula in treating melanoma, and suggests that SLE has the potential to be developed as a modern alternative and/or complimentary agent for melanoma treatment and prevention.
Highlights
Melanoma, a highly malignant neoplasm of the melanocytes, is the most aggressive form of skin cancer[1]
To determine whether SLE affects STAT3 activation, we examined the expression of phosphorylated STAT3 in tumor tissues by immunoblotting
In a traditional Chinese medicine (TCM) classic Yi Xue Qi Meng written 600 years ago, a herbal formula (SL) consisting of Sophorae Flos (SF) and Lonicerae Japonicae Flos (LJF) was documented to be used by Chinese medicine practitioners to treat skin diseases with TCM symptoms that resemble melanoma
Summary
A highly malignant neoplasm of the melanocytes, is the most aggressive form of skin cancer[1]. Currently available chemotherapeutics against malignant melanoma are often expensive, with toxic side effects, low response rates, and/or high tendency to develop tolerance[5,6,7,8]. These disappointing but harsh realities highlight the urgency of exploring novel, safe and effective alternative approaches for melanoma management. Constituents in SF and LJF, such as rutin, quercetin and luteolin, have been shown to possess anti-melanoma properties[22,23,24] Some of these constituents have been demonstrated to inhibit STAT3 signaling in different types of tumor cells[23, 25]. The involvement of STAT3 signaling in the anti-melanoma effects of SLE was explored
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