Artepillin C and Other Herbal PAK1-blockers: Effects on Hair Cell Proliferation and Related PAK1-dependent Biological Function in Cell Culture

Abstract

PAK1 (RAC/CDC42-activated kinase 1) is the major oncogenic kinase, and a number of herbal PAK1-blockers such as propolis and curcumin have been shown to be anti-oncogenic and anti-melanogenic as well as anti-alopecia (promoting hair growth). Previously, we found several distinct PAK1-inhibitors in Okinawa plants including Alpinia zerumbet (alpinia). Thus, here, we tested the effects of these herbal compounds and their derivatives on the growth of cancer or normal hair cells, and melanogenesis in cell culture of A549 lung cancer, hair follicle dermal papilla cell, and B16F10 melanoma. Among these herbal PAK1-inhibitors, cucurbitacin I from bitter melon (Goya) turned out to be the most potent to inhibit the growth of human lung cancer cells with the IC50 around 140 nM and to promote the growth of hair cells with the effective dose around 10 nM. Hispidin, a metabolite of 5,6-dehydrokawain from alpinia, inhibited the growth of cancer cells with the IC50 of 25 μM as does artepillin C, the major anti-cancer ingredient in Brazilian green propolis. Mimosine tetrapeptides (MFWY, MFYY, and MFFY) and hispidin derivatives (H1-3) also exhibited a strong anti-cancer activity with the IC50 ranging from 16 to 30 μM. Mimosine tetrapeptides and hispidin derivatives strongly suppressed the melanogenesis in melanoma cells.

Hispidin induces autophagic and necrotic death in SGC-7901 gastric cancer cells through lysosomal membrane permeabilization by inhibiting tubulin polymerization

“…This most likely resulted from the down- and up-regulation of the activity of at least two kinases, such as p21-activated kinase 1 (PAK1), Aurora B, CaMKII, and IV/G. In accord with this finding, hispidin strongly inhibited PAK1 (IC50 = 5.7 μM) [23–25], which promoted STMN1 dephosphorylation at Ser 16 . By contrast, LMP caused by microtubule depolymerization increased the free cytoplasmic calcium concentration, which up-regulated the activity of CaMKII and some other calcium-dependent kinases to enhance STMN1 phosphorylation at Ser 16 .…”

Review of Hair Follicle Dermal Papilla cells asin vitroscreening model for hair growth

“…The research on herbs and active constituents as hair growth promoters has been driven by their less toxicity, easy availability, low‐cost, patient compliance and more than one mode of biochemical action . Specific effects of herbal extracts, polyherbal formulations, flavonoids and natural compounds on DPCs have been examined . In vivo hair growth promoting effects as proof of concept are also mentioned.…”

Avaliação in Vitro Do Potencial Citotóxico Dos Óleos De Alpinia Speciosa, Ageratum Conyzoides E Dysphania Ambrosioides Em Linhagem Celular De Câncer De Próstata, Linfoma Histiocítico E Leucemia Mieloide Crônica

“…Compostos bioativos de A. speciosa têm sido referido por apresentarem bloqueadores de PAK-1, uma proteína chave associada a vários tipos de doenças incluindo o câncer. E por isso, atualmente tem sido extensivamente pesquisada como estratégia para a terapia do câncer (TAIRA;NGUYEN;TAWATA, 2017;NGUYEN at al., 2016). Estudos utilizando o extrato de A. conyzoides têm sido referido por apresentar efeito antitumoral em linhagens cancerígenas de carcinoma de pulmão humano (A-549), leucemia em rato (P-388) e humano (Jurkat) (MOMESSO et al, 2009;ACHEAMPONG et al, 2015).…”

“…Alpinia speciosa (Zingiberaceae) difundida na região do Nordeste do Brasil, apresenta propriedades anticâncer em linhagens de câncer de pulmão (TAIRA; NGUYEN; TAWATA, 2017). Dysphania ambrosioides (Amaranthaceae) com ampla distribuição no mundo e nativa da América Central e do Sul e possui um amplo espectro de atividade biológica e antitumoral (OLIVEIRA et al, 2014;SÁ et al, 2015). Ageratum conyzoides (Asteraceae) bastante difundida na região tropical e subtropical do mundo, possui ação anti-inflamatória, fungicida e inseticida, e atualmente sua ação antitumoral vem sendo relatada na literatura (MOMESSO et al, 2009).…”