Betulinic acid induces apoptosis in skin cancer cells and differentiation in normal human keratinocytes

Abstract

Betulinic acid (BA), a pentacyclic triterpene of plant origin, induces cell death in melanoma cells and other malignant cells of neuroectodermal origin. Little is known about additional biological effects in normal target cells. We show, in this study, that BA induces differentiation as well as cell death in normal human keratinocytes (NHK). Cytotoxicity profiles of BA are compared among normal human keratinocytes, HaCaT cells, IGR1 melanoma cells and normal melanocytes. As expected, BA is toxic to all cell types, normal and malignant, but varies in its cytotoxic potency and in the extent of induction of apoptotic vs. necrotic cell death in the four different skin cell types. Apoptosis is proved by annexin V and Apo2.7 binding and by DNA fragmentation. Induction of differentiation-associated antigens in keratinocytes--filaggrin and involucrin--is demonstrated, together with specific morphological changes in treated cell cultures. BA, apart from its cytotoxic activities in cellular systems, is capable of inducing differentiation of NHK into corneocytes without immediately provoking apoptotic cell death.

Betulinic Acid Inhibits Prostate Cancer Growth through Inhibition of Specificity Protein Transcription Factors

“…Moreover, because betulinic acid induces many other cytotoxic and proapoptotic effects in cancer cell lines (36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47), it is likely that down-regulation of Sp proteins differentially contributes to the overall effect of this compound. Current studies with betulinic acid are investigating tumor-type similarities and differences in its mechanism of action and the development of more potent analogues for clinical applications in the treatment of cancer.…”

“…It has been reported that betulinic acid induces apoptosis in several different cancer cell lines through multiple pathways, which include direct effects on the mitochondria accompanied by decreased mitochondrial membrane potential, up-regulation of death receptors, and interactions with other agents (36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47). In addition, betulinic acid exhibits antiangiogenic activity in an in vitro assay for tube-like structures in ECV304 cells (48); however, the underlying mechanisms of action for these responses are unknown.…”

Birch Bark Dry Extract by Supercritical Fluid Technology: Extract Characterisation and Use for Stabilisation of Semisolid Systems

“…antibacterial, antiviral, anti-parasite BE: [5,6]; BA: [7][8][9]; BE/BA: [10,11]; BE/BA/OA: [12]; LU/BA: [13]; OA/BA: [14] hepatoprotective BE: [15]; BE/BA: [16]; OA: [17][18][19][20]; LU: [21]; BA: [22] antitumor BE: [23,24]; BA: [25,26] BE/BA: [27,28]; LU: [29]; OA: [18,19,30] wound healing extract: [31][32][33]; BA: [34]; OA: [35,36] anti-inflammatory BE: [5,37]; LU: [38,39]; OA: [18,40] Apart from these pharmacological effects, birch bark extract is able to act as a gelling agent and Pickering emulsifier [41][42][43]. Together with its anti-inflammatory and wound healing effects, this makes birch bark dry extract interesting for the stabilisation of semisolid systems, such as gels and creams, acting as an active ingredient and an excipient in parallel.…”

Effects of betulinic acid on proliferation and apoptosis in Jurkat cells and its in vitro mechanism

“…Apoptosis is usually associated with cytoplasm shrinkage, nuclear alteration and DNA breakage [10] . And betulinic acid was also found to induce apoptosis of malignant melanoma [11] .…”